Combination therapy and / or prevention of cardiac disease in non-human mammals, comprising one or more SGLT-2 inhibitors and pimobendan and / or telmisartan.

Abstract

The present invention relates to the use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the prevention and / or treatment of one or more heart diseases in non-human mammals / non-human mammalian animals, such as dogs or cats.

Description

Technical Field

[0001] The present invention relates to the field of medicine, particularly to the field of veterinary medicine. The present invention relates to the combined treatment and / or prevention of one or more heart diseases in non-human mammals, particularly dogs or cats, comprising one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof and pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof.

Background Art

[0002] Recently, SGLT-2 inhibitors have been shown to reduce the risk of hospitalization for heart failure and the risk of new onset of heart failure events in human patients with type II diabetes. A program called EMPEROR was recently initiated to investigate whether empagliflozin has a beneficial effect in human patients with heart disease independent of diabetes. In EMPEROR-reduced, a phase III trial as part of the EMPEROR program, it was recently reported that empagliflozin reduced the risk of the composite endpoint of cardiovascular death or hospitalization due to heart failure in adults with heart failure with a reduced or maintained ejection fraction, regardless of diabetes.

[0003] <了 To date, SGLT-2 inhibitors have been used in clinical trials for different subsets of human patients with heart failure. However, the pathology of heart diseases in dogs and cats is significantly different from that observed in humans. For example, atherosclerosis, which is not reported in dogs or cats, is a major concern in humans. Cardiomyopathy is not a common cardiovascular disease in humans. Also, cardiomyopathy has been defined as an exclusion criterion for participation in clinical trials. (See McMurray JJV et al., Eur.J. Heart Fail. 2019; 21: 665-675; page 667, table 1, item 9). The latest therapeutic interventions are based on specific actions on unique pathways for the symptomatic treatment of secondary conditions induced by heart disease, for example, positive inotropic effects (improvement of myocardial contractility), ACE inhibitors, angiotensin receptor blockers (reduction of hypertension), and diuretics (increase in fluid excretion).

[0004] Known pharmaceutically active compounds for treating heart failure are disclosed in EP0008391 and have the formula:

Chemical formula

[0005]

Chemical formula

[0006] Telmisartan is already commercially available for human therapeutic / prophylactic use under the trademark Micardis® (Boehringer Ingelheim, Germany). Telmisartan exists in two polymorphic forms, as disclosed in WO00 / 043370, US6,358,986 and US6,410,742. The sodium salt of telmisartan, as well as its solvate, hydrate, and hemihydrate, are disclosed in WO2003 / 037876.

[0007] Primitive mesenchymal mitral valve disease ((M)MVD) and dilated cardiomyopathy (DCM) are the most common cardiovascular conditions in dogs and the most frequent cause of heart failure in canids. Furthermore, aortic stenosis, usually caused by a bulge or ring of fibrous tissue in the subaortic region (sub-aortic stenosis), is a common congenital defect in large breed dogs. These conditions have specific pathophysiologies, characterized by decreased pumping capacity, increased muscle effort, and energy imbalance, ultimately leading to heart failure. In humans, beneficial cardiovascular effects have been observed with the use of SGLT-2 inhibitors; however, their direct effects on the heart remain unclear. Also, the pathology of human heart disease (coronary disease, stroke, infarction) differs significantly from the conditions observed in dogs ((M)MVD, DCM). The American College of Veterinary Internal Medicine (ACVIM) consensus statement provides specific classification and treatment criteria for (M)MVD. While the guidelines target (M)MVD, the classification is generally used for other cardiac diseases such as DCM. The criteria define the different stages of canine cardiac disease as follows: - Stage A: The risk of developing heart failure in dogs is higher than average, but there are no obvious structural abnormalities at the time of examination (i.e., no audible heart murmur). - Stage B: Dogs in Stage B have structural abnormalities [e.g., the presence of (M)MVD], but have never shown clinical signs of heart failure associated with these diseases. Stage B is further divided into: Stage B1: Describes asymptomatic dogs for which there is no radiographic or ultrasound evidence of cardiac remodeling in response to canine (M)MVD, and where remodeling changes are present but not severe enough to meet the current clinical trial criteria used to determine whether initiation of treatment is warranted. Stage B2: Refers to asymptomatic dogs with hemodynamically severe, long-standing, and further-progressed mitral regurgitation, a condition sufficient to obtain radiographic and echocardiographic findings of left atrial and ventricular enlargement that meet the trial criteria used to identify dogs that would clearly benefit from initiating pharmacological treatment to delay the onset of heart failure. - Stage C: Dogs have (M)MVD that is severe enough to cause current or past clinical signs of heart failure. Stage C includes all dogs with (M)MVD that have experienced the manifestation of clinical symptoms of heart failure and are unresponsive to standard heart failure treatment. These affected animals remain classified as Stage C even after improvement or complete recovery of these clinical signs with standard treatment. In exceptional cases, such as successful mitral valve repair surgery, reclassification to Stage B is guaranteed. - Stage D: Refers to dogs with end-stage (M)MVD, in which clinical signs of heart failure are unresponsive to standard treatment (as defined later in this consensus statement). Such animals require advanced or specialized treatment strategies to remain clinically comfortable despite these conditions, and at some point, treatment efforts become futile without valve surgery. Similar to Stage C, the panel distinguishes between Stage D dogs requiring acute, hospital-based treatment and those that can be managed on an outpatient basis.

[0008] Standard treatment is usually recommended in stage B1 to slow disease progression, while clinical treatment is clearly required in stage B2. Management of heart failure is symptomatic relief, aiming to control clinical signs associated with the presence of edema and cavitary effusion. These are achieved through reducing preload and / or afterload with diuretics and vasodilators, improving cardiac performance (positive inotropes, positive lucitropes, antiarrhythmics), and using neurohormone modulators (ACE inhibitors, and potentially beta-blockers, aldosterone antagonists, and angiotensin II receptor blockers). Heart disease is one of the most common diseases in pet cats, affecting 10-15% of all cats (Freeman et al., Cardiol Res. 2017, 8(4): 139-142; Payne JR et al., J Vet Cardiol. 2015, 17(Suppl1): S244-S257).

[0009] Feline heart disease is classified into congenital and acquired heart disease. The majority of heart diseases are chronic, incurable, and progress over time. After an asymptomatic stage, clinical signs of heart failure and eventual cardiac death may occur. Typical symptoms of heart disease include: a weak general condition, weakness, lethargy, depression, feeding difficulties, tachycardia, tachypnea, dyspnea, congestion, edema, low peripheral blood pressure, and acute posterior or motor paralysis. Cardiomyopathy is the most common heart disease in cats. Cardiomyopathy is classified into primary cardiomyopathy (hypertrophic cardiomyopathy (HC / HCM / HOCM), restrictive cardiomyopathy (RCM), unclassifiable cardiomyopathy (UCM), arrhythmic right ventricular cardiomyopathy (ARVC), and dilated cardiomyopathy (DCM), which is very rare in cats) and secondary cardiomyopathy caused by nutritional deficiencies (taurine deficiency), metabolic disorders (hyperthyroidism, acromegaly), infiltrative processes (neoplasms, amyloidosis), and inflammatory processes (toxins, immune responses, infectious agents). The classification of cardiomyopathy is based on echocardiography. Cats are most commonly affected by hypertrophic cardiomyopathy (HCM), with a prevalence of 10-15% in the general pet cat population. However, due to hereditary forms, breeds such as Maine Coon, Persian, Ragdoll, and Sphynx cats are at higher risk.

[0010] While heart disease is common in cats, atherosclerosis, a major risk factor for heart failure in humans, is particularly absent in cats. This is at least in part related to the fact that these species have high-density lipoprotein concentrations (Freeman et al., Cardiol Res. 2017, 8(4): 139-142). In contrast to humans, feline cardiomyopathy is considered a major cause of heart failure in felines, but not much is known about the causes of different forms of the disease.

[0011] Clinical studies have shown mean survival times in cats with HCM ranging from 92 to 2,153 days, depending on the major clinical signs in the studied population (i.e., asymptomatic vs. congestive heart failure (CHF) vs. arterial thromboembolism (ATE)) (Atkins CE et al., J Am Vet Med Assoc. 1992, 201(4): 613-618; Rush JE et al., J Am Vet Med Assoc. 2002, 220(2): 202-207; Payne JR et al., J Vet Intern Med. 2013, 27(6): 1427-1436). Reported mean survival times for cats with HCM and heart failure range, for example, from as little as 92 to 563 days. Hoenig M et al. (J Vet Pharmacol Therapeutics 2018, 41(2): 266-273) have disclosed the therapeutic potential of the SGLT-2 inhibitor veragliflozin for treating diabetes in cats. Lin Y et al. (J Am Heart Assoc 2021, 10: e019274) have disclosed that dapagliflozin improves cardiac hemodynamics and mitigates arrhythmia-causing factors in mitral regurgitation-induced myocardial dysfunction. Little CJL et al. (J Small Anim Prac 2008, 49(1): 17-25) have reported that heart failure is common in diabetic cats. This finding comes from a retrospective case-control experiment in primary care settings. Matsumura K et al. (Cardiovascular Ultrasound 2019, 17(1): 26) have disclosed the effects of SGLT-2 inhibitors on cardiac function and cardiovascular outcomes. Nishinarity R et al. (J Am Heart Assoc 2021, 10:e017483) have disclosed that canagliflozin suppresses atrial remodeling in a canine model of atrial fibrillation. Santos-Gallego CG et al. (J American College Cardiol 2019, 73(15): 1931-1944) disclosed that empagliflozin improves adverse left ventricular remodeling in non-diabetic heart failure by promoting myocardial energy. Silva Custodio Jr J et al. (Heart Failure Reviews 2018, 23(3): 409-418) disclose the current concept of SGLT-2 inhibition and heart failure. U.S. Patent Application Publication No. 2011 / 098240 discloses a pharmaceutical composition comprising an SGLT-2 inhibitor in combination with a DPP IV inhibitor, which is suitable for the treatment or prevention of one or more conditions selected from type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance, and hyperglycemia.

[0012] US2015 / 164856 discloses one or more SGLT2 inhibitors or pharmaceutically acceptable forms thereof for use in the treatment and / or prevention of metabolic disorders in felines, preferably one or more selected from the group consisting of ketoacidosis, prediabetes, type 1 or type 2 diabetes mellitus, insulin resistance, obesity, hyperglycemia, impaired glucose tolerance, hyperinsulinemia, dyslipidemia, dyslipidemia, asymptomatic inflammation, systemic inflammation, low-grade systemic inflammation, hepatic lipidosis, atherosclerosis, pancreatic inflammation, neuropathy and / or syndrome X (metabolic syndrome) and / or loss of pancreatic beta-cell function, and / or remission of the metabolic disorder, preferably diabetic remission, is achieved and / or maintained.

[0013] US2016 / 000816 discloses certain SGLT-2 inhibitors for treating and / or preventing oxidative stress in human patients, for example, those with type 1 or type 2 diabetes, and the use of such SGLT-2 inhibitors for treating and / or preventing cardiovascular disease in human patients, for example, those with type 1 or type 2 diabetes. US2017 / 266152 discloses a method for preventing or treating acute or chronic heart failure, and for reducing the risk of cardiovascular death and hospitalization for heart failure and other conditions, by administering empagliflozin to human patients with preserved or reduced ejection fraction.

[0014] U.S. Patent Application Publication 2019 / 076395 discloses the use of certain SGLT-2 inhibitors, such as ertugliflozin or a pharmaceutically acceptable salt or cocrystal thereof, to treat, reduce the risk of, and / or prevent heart failure, myocardial infarction, cardiovascular disease, or cardiovascular death in animals without type 2 diabetes or type 1 diabetes, or in animals with prediabetes, or in animals with type 2 diabetes, type 1 diabetes, or prediabetes. U.S. Patent No. 10,537,570 discloses the use of pimobendan in a manner to reduce cardiac size and / or delay the onset of clinical symptoms in patients with asymptomatic (latent, preclinical) heart failure due to mitral valve disease. WO2005 / 092343 describes the use of PDE-III inhibitors, such as pimobendan, to reduce cardiac size in patients with heart failure, but does not describe patients with asymptomatic (latent, preclinical) heart failure due to mitral valve disease (MVD). WO2007 / 054514 addresses the use of PDE-III inhibitors, such as pimobendan, for the treatment of asymptomatic (also known as latent or preclinical) heart failure, but does not describe patients with asymptomatic (latent, preclinical) heart failure due to mitral valve disease (MVD). WO2011 / 153953 discloses the crystalline form of benzylbenzene SGLT-2 inhibitors, and in particular describes their use in the treatment of chronic heart failure in humans.

[0015] WO2017 / 174571 discloses a pimobendan for use in a method to reduce cardiac size and / or delay the onset of clinical symptoms in a patient suffering from asymptomatic (latent, preclinical) heart failure, preferably congestive heart failure, due to mitral valve disease (MVD), wherein the patient is preferably a mammal, more preferably human, dog, cat or horse, and most preferably dog.

[0016] WO2019 / 059557 and US2020 / 054656 disclose pharmaceutical compositions comprising an SGLT-2 inhibitor and a therapeutic agent for treating hypertension. WO2021 / 092341 and US2023 / 000816 disclose transporter inhibitor-linked sodium-glucose for addressing chronic kidney disease, hypertension, and heart failure in companion animals. WO2021 / 165177 and US2021 / 260090 disclose the use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof for the prevention and / or treatment of one or more heart diseases in felines. WO2022 / 036506 discloses fixed-dose combinations of compositions comprising an SGLT-2 inhibitor and an angiotensin receptor blocker. WO2023 / 006718 discloses the use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof for the prevention and / or treatment of one or more heart diseases in non-human mammals / non-human mammals other than felines, particularly dogs / canine animals. Despite the disclosures in the above literature, there is a medical need for combination therapy and / or prevention of cardiac disease in non-human mammals (affected animals), particularly dogs (affected animals) or cats (affected animals). [Overview of the project]

[0017] The present invention relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use as a pharmaceutical. In one aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use disclosed and / or claimed herein in a method of preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines.

[0018] The present invention also includes a corresponding method for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such non-human mammals / non-human mammalian animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals.

[0019] In another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for use disclosed and / or claimed herein in a method of treating one or more cardiac diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines.

[0020] The present invention also includes corresponding methods for treating one or more cardiac diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such non-human mammals / non-human mammalian animals, and corresponding uses of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for treating one or more cardiac diseases in non-human mammals / non-human mammalian animals.

[0021] In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use disclosed and / or claimed herein, wherein one or more cardiac diseases are acquired; congenital cardiac diseases; heart failure; congestive heart failure; asymptomatic / preclinical / occult heart failure; (primitive mesenchymal) mitral valve disease [(M)MVD]. Heart failure caused by (primitive mesenchymal) mitral valve disease [(M)MVD]; asymptomatic / preclinical / latent heart failure caused by (primitive mesenchymal) mitral valve disease [(M)MVD]; (primitive mesenchymal) mitral valve disease [(M)MVD]; clinically evident (primitive mesenchymal) mitral valve disease [(M)MVD]; asymptomatic / preclinical / latent (primitive mesenchymal) mitral valve disease [(M)MVD]; heart failure caused by dilated cardiomyopathy (DCM); heart failure caused by dilated cardiomyopathy (DCM) Congestive heart failure; asymptomatic / preclinical / latent heart failure due to dilated cardiomyopathy (DCM); dilated cardiomyopathy (DCM); clinically evident dilated cardiomyopathy (DCM); asymptomatic / preclinical / latent dilated cardiomyopathy (DCM); aortic stenosis (valve, supravalvular and / or subvalvular); heart failure due to one or more cardiomyopathy, heart failure due to hypertrophic cardiomyopathy (HCM), heart failure due to hypertrophic obstructive cardiomyopathy (HOCM), heart failure due to restrictive cardiomyopathy (RCM), This invention relates to one or more SGLT-2 inhibitors selected from the group consisting of heart failure due to dilated cardiomyopathy (DCM), heart failure due to unclassified cardiomyopathy (UCM), heart failure due to arrhythmic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), hypertrophic obstructive cardiomyopathy (HOCM), restrictive cardiomyopathy (RCM), dilated cardiomyopathy (DCM), unclassified cardiomyopathy (UCM), and / or arrhythmic right ventricular cardiomyopathy (ARVC), or a pharmaceutically acceptable form thereof.

[0022] The present invention also includes a corresponding method for preventing and / or treating one or more of the cardiovascular diseases exemplified above in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such non-human mammals / non-human mammalian animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more of the cardiovascular diseases exemplified above in non-human mammals / non-human mammalian animals.

[0023] In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use disclosed and / or claimed herein, wherein one or more cardiac diseases are acquired heart disease; congenital heart disease; heart failure; congestive heart failure; asymptomatic / preclinical / latent heart failure; (primitive mesenchymal) mitral valve disease [(M)MVD]; clinically apparent (primitive mesenchymal) mitral valve disease [(M)MVD]; asymptomatic / preclinical / latent (primitive mesenchymal) mitral valve disease [(M)MVD]; dilated heart The present invention relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, selected from the group consisting of myopathy (DCM); clinically evident dilated cardiomyopathy (DCM); asymptomatic / preclinical / latent dilated cardiomyopathy (DCM); and aortic stenosis (valvular, supravalvular and / or subvalvular), wherein the non-human mammal / non-human mammalian patient is a canid / canid patient, preferably a canid patient requiring such prophylaxis and / or treatment, more preferably a dog requiring such prophylaxis and / or treatment, and even more preferably a non-diabetic dog requiring such prophylaxis and / or treatment.

[0024] The present invention also includes a corresponding method for preventing and / or treating one or more of the cardiovascular diseases exemplified above in canids / canid animals, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such canids / canid animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more of the cardiovascular diseases exemplified above in canids / canid animals.

[0025] In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use disclosed and / or claimed herein, wherein one or more cardiac diseases are (primitive mesenchymal) mitral valve disease [(M)MVD]; clinically apparent (primitive mesenchymal) mitral valve disease [(M)MVD]; asymptomatic / preclinical / latent (primitive mesenchymal) mitral valve disease [(M)MVD]; dilated cardiomyopathy (DCM); clinical The present invention relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, selected from the group consisting of obvious dilated cardiomyopathy (DCM); asymptomatic / preclinical / latent dilated cardiomyopathy (DCM), wherein the non-human mammal / non-human mammalian patient is a canid / canid patient, preferably a canid patient requiring such prophylaxis and / or treatment, more preferably a dog requiring such prophylaxis and / or treatment, and even more preferably a non-diabetic dog requiring such prophylaxis and / or treatment.

[0026] The present invention also includes a corresponding method for preventing and / or treating one or more of the cardiovascular diseases exemplified above in canids / canid animals, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such canids / canid animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more of the cardiovascular diseases exemplified above in canids / canid animals.

[0027] In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use disclosed and / or claimed herein, wherein one or more cardiac diseases are acquired; congenital cardiac diseases; heart failure; congestive heart failure; asymptomatic / preclinical / occult heart failure; heart failure due to one or more cardiomyopathy, heart failure due to hypertrophic cardiomyopathy (HCM), heart failure due to hypertrophic obstructive cardiomyopathy (HOCM), heart failure due to restrictive cardiomyopathy (RCM), heart failure due to dilated cardiomyopathy (DCM), heart failure due to unclassifiable cardiomyopathy (UCM), The present invention relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, selected from the group consisting of heart failure due to arrhythmic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), hypertrophic obstructive cardiomyopathy (HOCM), restrictive cardiomyopathy (RCM), dilated cardiomyopathy (DCM), unclassifiable cardiomyopathy (UCM), and / or arrhythmic right ventricular cardiomyopathy (ARVC), wherein the non-human mammal / non-human mammalian patient is a feline / feline patient, preferably a feline patient requiring such prophylaxis and / or treatment, more preferably a cat requiring such prophylaxis and / or treatment, and even more preferably a non-diabetic cat requiring such prophylaxis and / or treatment.

[0028] The present invention also includes a corresponding method for preventing and / or treating one or more of the cardiovascular diseases exemplified above in felines / feline animals, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such felines / feline animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more of the cardiovascular diseases exemplified above in felines / feline animals.

[0029] In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof, for use disclosed and / or claimed herein, wherein one or more cardiac diseases are selected from the group consisting of hypertrophic cardiomyopathy (HCM)-induced heart failure; hypertrophic cardiomyopathy (HCM), and the non-human mammal / non-human mammalian patient is a feline / feline patient, preferably a feline patient requiring such prevention and / or treatment, more preferably a cat requiring such prevention and / or treatment, and even more preferably a non-diabetic cat requiring such prevention and / or treatment, one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof.

[0030] The present invention also includes a corresponding method for preventing and / or treating one or more of the cardiovascular diseases exemplified above in felines / feline animals, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such felines / feline animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more of the cardiovascular diseases exemplified above in felines / feline animals.

[0031] In yet another aspect, the present invention also relates to the following preferred embodiments: One or more SGLT-2 inhibitors, or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use in methods of preventing and / or treating DCM or MVD in canids / canid animals. One or more SGLT-2 inhibitors, or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use in methods of preventing and / or treating HCM in felines / feline animals. One or more SGLT-2 inhibitors, or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use in methods of treating DCM or MVD in canids / canid animals. One or more SGLT-2 inhibitors, or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use in methods of treating HCM in felines / feline animals. One or more SGLT-2 inhibitors in combination with pimobendan, or any pharmaceutically acceptable form thereof, for use in methods of treating DCM or MVD in canids / canid animals. One or more SGLT-2 inhibitors in combination with pimobendan, or any pharmaceutically acceptable form thereof, for use in methods of treating HCM in felines / feline animals.

[0032] In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use disclosed and / or claimed herein, wherein one or more SGLT-2 inhibitors are (1) Glucopyranosyl-substituted benzene derivative of formula (1) [ka] (In the formula, R 1 represents cyano, Cl, or methyl (most preferably cyano), R 2 represents H, methyl, methoxy, or hydroxy (most preferably H), R 3This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propa-1-yl, and 3-hydroxy-3-methylbuta -1-yl, 1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl, 2-methoxy-ethyl, 2-ethoxy-ethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxyethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano, R 3 The compound is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy, most preferably R 3 (It is cyclopropyl.) or a derivative thereof, wherein one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 Acylated with a group selected from -alkyl)-carbonyl groups;

[0033] (2) Veragliflozin represented by formula (2): [ka]

[0034] (3) Dapagliflozin represented by formula (3): [ka]

[0035] (4) Canagliflozin represented by formula (4): [ka]

[0036] (5) Empagliflozin represented by formula (5): [ka] (6) Luseogliflozin represented by formula (6): [ka]

[0037] (7) Tofogliflozin represented by formula (7): [ka]

[0038] (8) Ipragliflozin represented by formula (8): [ka]

[0039] (9) Erzggliflozin represented by formula (9): [ka]

[0040] (10) Atigliflozin represented by formula (10): [ka]

[0041] (11) Remogliflozin represented by formula (11):

Chemical formula

[0042] (11A) Remogliflozin etabonate represented by formula (11A):

Chemical formula

[0043] (12) Thiophene derivative of formula (12)

Chemical formula

[0044] (13) 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene represented by formula (13):

Chemical formula

[0045] (14) Spiroketal derivative of formula (14):

Chemical formula

[0046] (15) Pyrazole-O-glucoside derivative of formula (15):

Chemical formula

[0047] (16) Sotagliflozin represented by formula (16): [ka]

[0048] (17) Cergliflozin represented by formula (17): [ka]

[0049] (18) Compounds represented by formula (18): [ka] (In the formula, R 3This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propane-1-yl, 3-hydroxy- 3-methylbuta-1-yl, 1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethylethyl, 2-methoxyethyl, 2-ethoxyethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxyethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano, R 3 The compound is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy, most preferably R 3 (It is cyclopropyl), or a derivative thereof, wherein one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 Acylated with a group selected from -alkyl)-carbonyl groups;

[0050] (19) Bexagliflozin represented by formula (19): [ka]

[0051] (20) Janagliflozin represented by formula (20): [ka]

[0052] (21) Long liflozin represented by formula (21): [ka] (22) Wampagliflozin; (23) Enabogliflozin represented by formula (23): [ka] (24) TFC-039 represented by formula (24): [ka] This relates to one or more SGLT-2 inhibitors selected from the group consisting of the following, or to a pharmaceutically acceptable form thereof.

[0053] The present invention also includes a corresponding method for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, as exemplified above, in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof, to such non-human mammals / non-human mammalian animals; and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, as exemplified above, in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof, for the preparation of a medicament for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals.

[0054] In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use disclosed and / or claimed herein, wherein the pharmaceutically acceptable form is a crystalline complex of one or more SGLT-2 inhibitors and one or more amino acids, preferably proline, more preferably L-proline, and most preferably a cocrystal of one or more SGLT2 inhibitors, L-proline, and water of crystallization.

[0055] The present invention also includes a corresponding method for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such non-human mammals / non-human mammalian animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals.

[0056] In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof for use disclosed and / or claimed herein, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, wherein veragliflozin or a pharmaceutically acceptable form thereof is administered as a single SGLT-2 inhibitor in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, preferably veragliflozin or a pharmaceutically acceptable form thereof is administered as a single SGLT-2 inhibitor in combination with pimobendan, or bexagliflozin or a pharmaceutically acceptable form thereof is administered as a single SGLT-2 inhibitor in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, preferably bexagliflozin or a pharmaceutically acceptable form thereof is administered as a single SGLT-2 inhibitor in combination with pimobendan. In a preferred embodiment, veragliflozin or a pharmaceutically acceptable form thereof is combined with pimobendan alone. In another embodiment, veragliflozin or a pharmaceutically acceptable form thereof is combined with pimobendan and telmisartan or a pharmaceutically acceptable form thereof. In another embodiment, veragliflozin or a pharmaceutically acceptable form thereof is combined with telmisartan or a pharmaceutically acceptable form thereof. In another preferred embodiment, bexagliflozin or a pharmaceutically acceptable form thereof is combined with pimobendan alone. In another embodiment, bexagliflozin or a pharmaceutically acceptable form thereof is combined with pimobendan and telmisartan or a pharmaceutically acceptable form thereof. In another embodiment, bexagliflozin or a pharmaceutically acceptable form thereof is combined with telmisartan or a pharmaceutically acceptable form thereof.

[0057] Therefore, the present invention also relates to the following more preferred embodiments: Veragliflozin or a pharmaceutically acceptable form thereof as a single SGLT-2 inhibitor, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use in methods of preventing and / or treating DCM or MVD in canids / canid animals. Veragliflozin or a pharmaceutically acceptable form thereof as a single SGLT-2 inhibitor, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use in methods of preventing and / or treating HCM in felines / feline animals.

[0058] Veragliflozin or a pharmaceutically acceptable form thereof as a single SGLT-2 inhibitor in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use in methods of treating DCM or MVD in canids / canid animals. Veragliflozin or a pharmaceutically acceptable form thereof as a single SGLT-2 inhibitor in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use in methods of treating HCM in felines / feline animals. Veragliflozin or any pharmaceutically acceptable form thereof, as a single SGLT-2 inhibitor in combination with pimobendan, for use in methods of treating DCM or MVD in canids / canid animals. Veragliflozin or any pharmaceutically acceptable form thereof, as a single SGLT-2 inhibitor in combination with pimobendan, for use in methods of treating HCM in felines / feline animals.

[0059] The present invention also relates to the following particularly preferred embodiments: Veragliflozin or a pharmaceutically acceptable form thereof as a single SGLT-2 inhibitor, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use in methods of preventing and / or treating DCM or MVD in canids / canid animals. Veragliflozin or a pharmaceutically acceptable form thereof as a single SGLT-2 inhibitor, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use in methods of preventing and / or treating HCM in felines / feline animals.

[0060] Veragliflozin or a pharmaceutically acceptable form thereof as a single SGLT-2 inhibitor in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use in methods of treating DCM or MVD in canids / canid animals. Veragliflozin or a pharmaceutically acceptable form thereof as a single SGLT-2 inhibitor in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use in methods of treating HCM in felines / feline animals. Veragliflozin or any pharmaceutically acceptable form thereof, as a single SGLT-2 inhibitor in combination with pimobendan, for use in methods of treating DCM or MVD in canids / canid animals. Veragliflozin or any pharmaceutically acceptable form thereof, as a single SGLT-2 inhibitor in combination with pimobendan, for use in methods of treating HCM in felines / feline animals.

[0061] The present invention also includes a corresponding method for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such non-human mammals / non-human mammalian animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals. In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use disclosed and / or claimed herein, wherein one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof are administered orally, parenterally, intravenously, subcutaneously or intramuscularly, preferably orally.

[0062] The present invention also includes a corresponding method for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such non-human mammals / non-human mammalian animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals.

[0063] In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use disclosed and / or claimed herein, wherein one or more SGLT-2 inhibitors or a pharmaceutically acceptable form thereof is administered at a dose of 0.01 mg / kg body weight to 10 mg / kg body weight per day, preferably 0.01 mg / kg body weight to 5 mg / kg body weight per day, more preferably 0.01 mg / kg body weight to 4 mg / kg body weight per day This invention relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, administered in doses of kg body weight, more preferably 0.01 mg / kg body weight to 3 mg / kg body weight per day, more preferably 0.01 mg / kg body weight to 2 mg / kg body weight per day, more preferably 0.01 mg / kg body weight to 1 mg / kg body weight per day, more preferably 0.01 mg / kg body weight to 0.5 mg / kg body weight per day, and most preferably 0.01 mg / kg body weight to 0.3 mg / kg body weight per day. Instead, one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof are administered in doses of 0.1 mg / kg body weight to 10 mg / kg body weight per day, preferably 0.1 mg / kg body weight to 5 mg / kg body weight per day, more preferably 0.1 mg / kg body weight to 4 mg / kg body weight per day, even more preferably 0.1 mg / kg body weight to 3 mg / kg body weight per day, even more preferably 0.1 mg / kg body weight to 2 mg / kg body weight per day, even more preferably 0.1 mg / kg body weight to 1 mg / kg body weight per day, even more preferably 0.1 mg / kg body weight to 0.5 mg / kg body weight per day, and most preferably 0.1 mg / kg body weight to 0.3 mg / kg body weight per day.

[0064] The present invention also includes a corresponding method for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such non-human mammals / non-human mammalian animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals. In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use disclosed and / or claimed herein, wherein such one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof are administered once or twice daily, preferably once daily.

[0065] The present invention also includes a corresponding method for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such non-human mammals / non-human mammalian animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals.

[0066] In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use disclosed and / or claimed herein, wherein pimobendan is administered at a dose of 0.1 mg / kg body weight to 1 mg / kg body weight per day, preferably 0.2 mg / kg body weight to 0.6 mg / kg body weight per day, more preferably 0.5 mg / kg body weight per day.

[0067] The present invention also includes a corresponding method for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such non-human mammals / non-human mammalian animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals. In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use disclosed and / or claimed herein, wherein pimobendan is administered once or twice daily, preferably twice daily, more preferably every 12 hours.

[0068] The present invention also includes a corresponding method for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such non-human mammals / non-human mammalian animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals.

[0069] In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for use disclosed and / or claimed herein, wherein one or more SGLT-2 inhibitors are administered in combination with pimobendan and telmisartan or pharmaceutically acceptable forms thereof, preferably one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof are administered before, after, or concurrently with the administration of pimobendan and telmisartan or pharmaceutically acceptable forms thereof.

[0070] The present invention also includes a corresponding method for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such non-human mammals / non-human mammalian animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals.

[0071] In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use disclosed and / or claimed herein, wherein telmisartan or a pharmaceutically acceptable form thereof is administered in doses of 0.01 to 10 mg / kg body weight per day, preferably 0.05 to 8 mg / kg body weight per day, more preferably 0.1 to 5 mg / kg body weight per day, more preferably 0.2 to 4 mg / kg body weight per day, more preferably 0.3 to 3 mg / kg body weight per day, more preferably 0.4 to 2.5 mg / kg body weight per day, more preferably 0.5 to 2 mg / kg body weight per day, and most preferably 0.75 to 1.5 mg / kg body weight per day.

[0072] The present invention also includes a corresponding method for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such non-human mammals / non-human mammalian animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals. In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use disclosed and / or claimed herein, wherein telmisartan or a pharmaceutically acceptable form thereof is administered once or twice daily, preferably once daily.

[0073] The present invention also includes a corresponding method for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such non-human mammals / non-human mammalian animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals.

[0074] In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use disclosed and / or claimed herein, wherein the prophylactic and / or therapeutic effect is one or more of the following clinical and / or biochemical parameters: - Improved cardiovascular metabolic efficiency characterized by an increased ratio of [cardiac output / metabolic substrates consumed] and / or an increased ratio of [cardiac output / oxygen consumed]; - Increased ketone body production in the liver, characterized by increased plasma levels of 3-hydroxybutyrate and / or the corresponding acylcarnitine, i.e., hydroxybutyrylcarnitine, and increased plasma levels of one or more branched-chain amino acids (valine, leucine, and isoleucine); - Improved cardiac function and improved arterial wall structural function achieved by reducing preload and / or afterload; - Improved cardiac ultrasound parameters, e.g., reduced LA (left atrial dimension measured as the right parasternal short axis), LA / Ao (left atrial to aortic ratio; Ao = diameter of the aortic root), IVSd (cardiac diastolic dimension of the terminal ventricular septum, i.e., thickness of the ventricular septum), and / or LAD (left atrial dimension measured as the right parasternal long axis), as well as improved cardiac biomarkers, e.g., reduced NT-proBNP (N-terminal pro-brain natriuretic peptide) and / or reduced cTnI (cardiac troponin I) and / or increased erythropoietin concentration, and / or changes in metabolites indicating changes in the cardiac energy source; and improved heart murmurs; - Delay in the onset of different phenotypic cardiac diseases, e.g., (M)MVD and / or DCM and / or cardiomyopathy, preferably a delay of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 months or longer, or furthermore, cessation of the progression of different phenotypic cardiac diseases, e.g., (M)MVD and / or DCM, and / or cardiomyopathy; - An extension of survival time, preferably at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 months or longer, and / or a delay in the onset of the following symptoms of heart failure, preferably at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 months or longer, and / or a lower level of cardiac mortality and / or morbidity; - Improved clinical signs, such as shortness of breath or difficulty breathing, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension and / or decreased polydipsia; - Prolonged time to an event (e.g., heart failure, cardiac death, onset of clinical signs, need for additional concomitant medications, increased dose of concomitant therapy-diuretics); - Prevention of fibrosis; - Prevention of cardiomyocyte death / protection of cardiomyocytes (reduction of oxidative stress); - Increased flexibility of blood vessel walls; - Prevention of high blood pressure; - A higher quality of life This relates to one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, characterized by the above.

[0075] The present invention also includes a corresponding method for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines, comprising administering one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof to such non-human mammals / non-human mammalian animals, and a corresponding use of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for the preparation of a medicament for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals.

[0076] In yet another aspect, the present invention also relates to a pharmaceutical composition comprising one or more SGLT2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof, for use disclosed and / or claimed herein, wherein the pharmaceutical composition is a fixed-dose combination (FDC) of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof and pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof, and more preferably the FDC is a solid or liquid formulation.

[0077] In yet another aspect, the present invention also relates to one or more SGLT-2 inhibitors disclosed and / or claimed herein or pharmaceutically acceptable forms thereof for use as a diuretic in non-human mammals, optionally in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, particularly for use in the prevention and / or treatment of congestion, preferably in the prevention and / or treatment of fluid congestion (e.g., in heart failure, acute heart failure, congestive heart failure, edema, pulmonary edema, pulmonary congestion, ascites, and reduction of the load on the heart and arteries), and / or in the reduction of excess body volume, e.g., fluid retention in body cavities, acute tissue edema, and / or asthma, and / or in forced diuresis (e.g., oliguria, intoxication).

[0078] In one preferred embodiment, veragliflozin or a pharmaceutically acceptable form thereof is optionally used in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof as a diuretic, particularly in the prevention and / or treatment of congestion, preferably in the prevention and / or treatment of fluid congestion (e.g., in heart failure, acute heart failure, congestive heart failure, edema, pulmonary edema, pulmonary congestion, ascites, and in reducing the burden on the heart and arteries), and / or in the reduction of fluid volume excess, e.g., fluid retention in body cavities, acute tissue edema, and / or asthma, and / or as an adjunct to forced diuresis (e.g., oliguria, intoxication). In another preferred embodiment, bexagliflozin or a pharmaceutically acceptable form thereof is optionally used in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof as a diuretic, particularly in the prevention and / or treatment of congestion, preferably in the prevention and / or treatment of fluid congestion (e.g., in heart failure, acute heart failure, congestive heart failure, edema, pulmonary edema, pulmonary congestion, ascites, and in reducing the load on the heart and arteries), and / or in the reduction of fluid volume excess, e.g., fluid retention in body cavities, acute tissue edema, and / or asthma, and / or as an adjunct to forced diuresis (e.g., oliguria, intoxication).

[0079] In nonhuman mammals / nonhuman mammalian animals with illnesses, particularly in the prevention and / or treatment of congestion, preferably in nonhuman mammals / nonhuman mammalian animals with illnesses, particularly in canids / canid animals with illnesses or felids / felid animals with illnesses, the corresponding method of using one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof as diuretics, optionally in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof, in the prevention and / or treatment of fluid congestion (e.g., in heart failure, acute heart failure, congestive heart failure, edema, pulmonary edema, pulmonary congestion, ascites, and reduction of the burden on the heart and arteries), and / or in the reduction of excess body volume, e.g., fluid retention in body cavities, acute tissue edema, and / or in the reduction of asthma, and / or in the adjunct of forced diuresis (e.g., oliguria, poisoning), wherein one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof as disclosed and / or claimed herein are used as diuretics, optionally in combination with one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof The present invention also includes the corresponding use of one or more SGLT-2 inhibitors or diuretics of pharmaceutically acceptable forms thereof, optionally combined with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for the preparation of pharmaceuticals for the prevention and / or treatment of congestion, preferably for the prevention and / or treatment of fluid congestion (e.g., in heart failure, acute heart failure, congestive heart failure, edema, pulmonary edema, pulmonary congestion, ascites, and the reduction of the burden on the heart and arteries) in nonhuman mammals / nonhuman mammals, and for the reduction of excess body volume, e.g., fluid retention in body cavities, acute tissue edema, and / or asthma, and / or for the adjunct of forced diuresis (e.g., oliguria, intoxication).

[0080] The advantages of the present invention are one or more of the following: - Reduction in the doses of individual active ingredients (independent of each other) compared to each individual treatment, and / or replacement with further combination therapies (e.g., diuretics). - Dose reduction of further combination therapy (e.g., diuretics) compared to standard care procedures. - Higher cardiac efficiency - Increased cardiomyocyte protection - Reduced side effects (e.g., cardiac death, hospitalization). [Modes for carrying out the invention]

[0081] Before embodiments of the present invention are described in further detail, it should be noted that, as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural references unless the context explicitly indicates otherwise.

[0082] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art in which the invention pertains. All given ranges and values ​​may vary by 1 to 5 percent unless otherwise shown or otherwise known by those skilled in the art, and therefore the term “about” is usually omitted from descriptions and claims. Any methods and materials similar or equivalent to those described herein may be used in carrying out or testing the invention, but preferred methods, devices, and materials are described herein. All publications described herein are incorporated herein by reference for the purpose of describing and disclosing substances, excipients, carriers, and methodologies, as reported in publications that may be used in connection with the invention. Nothing herein shall be construed as an agreement by which the invention has no prior rights to such disclosures by prior inventions. In a preferred embodiment, the “non-human mammal” is selected from the group consisting of cattle, canids, goats, horses, felines, lagomorphs, sheep, pigs, and rodents; more preferably from the group consisting of cattle, cows, dogs, cats, goats, horses, ponies, donkeys, sheep, pigs, rabbits, rats, and mice; even more preferably from the group consisting of canids or felines; and most preferably from the group consisting of dogs or cats.

[0083] In the course of this invention, the term "canidae" or "canine animal" refers to any member of the family Canidae (i.e., the genus Canis of the family Canidae). Thus, it may belong to either the subfamily Canidae or the subfamily Canis of the family Canidae. The term "canidae" includes the term dog, for example, the domesticated dog. The term domesticated dog includes the terms Canis familiaris or Canis lupus familiaris. Most preferably, "canidae" or "canine animal" refers to a dog, especially a domesticated dog. In the course of this invention, the term “feline” refers to all members of the family Felidae (i.e., felid). Thus, it may belong to either the subfamily Felinae or the subfamily Pantherinae. The term “feline” includes the term cat, e.g., domesticated cat. The term domesticated cat includes the terms Felis catus and feline animal (feline). Most preferably, “feline” refers to a cat, especially a domesticated cat.

[0084] In cats, the most common sign of heart failure is the onset of difficulty breathing (dyspnea) and / or more rapid breathing (tachypnea). This is generally caused by fluid accumulation in the thoracic cavity surrounding the lungs (called pleural effusion) or fluid accumulation within the lungs themselves (called pulmonary edema). Along with dyspnea, cats may also have cold extremities (e.g., ears and paws) and pale mucous membranes (gums and eyes), suggesting poor circulation. Sometimes, the mucous membranes of the mouth and eyes, and even the skin, may show signs of cyanosis (a bluish tint). All of these clinical signs of heart failure improve or are clinically delayed in cats after treatment with SGLT-2 inhibitors compared to the disease's progression in untreated cats.

[0085] Another sign that can occur in cats with cardiomyopathy, sometimes even the primary indicator of the underlying heart disease, is the onset of a condition known as feline aortic thromboembolism (FATE). In cats with cardiomyopathy, a thrombus (blood clot) can form in one of the ventricles (usually the left atrium) of the heart. This occurs primarily because blood does not normally flow through the heart. The thrombus, or blood clot, initially adheres to the heart wall but can detach and be carried away by the blood, leaving the heart. A thrombus that has entered the bloodstream is called an embolus, hence the term "thromboembolism." Once in circulation, these embolus can remain in small arteries and block the flow of blood to areas of the body. This can occur in several different locations, but is more commonly seen towards the extremities as the major arteries leaving the heart (aorta) divide to supply blood to the hind legs. This complication is most commonly seen in HCM and causes the sudden onset of motor paralysis in one or both hind legs, accompanied by severe pain and considerable distress. Furthermore, this clinical sign of heart failure is improved / delayed, or its onset is clinically relevant, in cats treated with SGLT-2 inhibitors in combination with pimobendan and / or telmisartan or its pharmaceutically acceptable forms, compared to the onset of the disease in untreated cats. It is preferably delayed by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 months or longer. Overall, the survival time of cats with cardiac disease(s) after treatment with SGLT-2 inhibitors in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof was clinically increased by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 months or longer, preferably at least 6 months, compared to untreated cats with cardiac disease(s). In the course of this invention, the term "heart disease" is synonymous with "cardiac disease" and refers to any disorder or deformity of the heart itself that affects the structure and function of the heart. There are many types of heart diseases that occur in different ways and affect organs in different parts of the body, including congenital heart defects (e.g., septal defects, occlusion defects), arrhythmias (e.g., tachycardia, bradycardia, and fibrillation), and cardiomyopathy.

[0086] In the course of this invention, the term “heart failure” is also known as congestive heart failure and congestive heart failure, and refers to a pathophysiological process in which the heart is unable to pump enough blood to maintain blood flow through the body to meet the metabolic requirements (oxygen and substrates) of peripheral tissues and organs. It can also be defined as a complex clinical syndrome characterized by symptoms such as reduced exercise tolerance, dyspnea, fatigue, fluid retention, and reduced lifespan, based on an abnormal structure or function of the heart. This can be divided into systolic failure, in which the pumping of blood from the heart during systole is affected, and diastolic failure, in which the heart is unable to receive sufficient blood at low pressure into the ventricular cavity during diastole. The majority of these are chronic diseases resulting from chronic overload of the heart or occurring after acute hemodynamic stress due to fluid overload, valvular dysfunction, or myocardial infarction.

[0087] In the course of this invention, the term "cardiomyopathy" refers to a group of diseases affecting the myocardium, which are the most common forms of heart disease found in cats and the most common cause of heart failure. Cardiomyopathy is described by the effects these diseases have on the structure and function of the myocardium. Types of cardiomyopathy include: hypertrophic cardiomyopathy (HCM), hypertrophic obstructive cardiomyopathy (HOCM), restrictive cardiomyopathy (RCM), unclassifiable cardiomyopathy (UCM), arrhythmic right ventricular cardiomyopathy (ARVC), and dilated cardiomyopathy (DCM). Classification is based on echocardiography.

[0088] Hypertrophic cardiomyopathy (HCM) is the most prevalent feline cardiac disorder. While HCM most commonly affects middle-aged cats (average 6.5 years), all ages can be affected. A male predisposition exists (>75%). In humans, a significant genetic predisposition to HCM is present in 55% of cases. In humans, the disorder can be congenital or acquired and likely constitutes a single group of diseases. The cause of HCM in felines is unknown, but Persian and Maine Coon cats appear to be more susceptible to certain case lines, suggesting a genetic influence. HCM is associated with marked left ventricular hypertrophy, as in cases of systemic hypertension, hyperthyroidism, and aortic stenosis, although the underlying cause cannot be identified in these cases. Cardiac lesions are characterized by severe concentric hypertrophy of the left ventricle and secondary left atrial dilation. Asymmetrical septal thickening (ASH) is present in the majority of dogs and humans with HCM, but only in 30% of cats with HCM. Histologically complex arrangement of cardiac myofibrils has been reported in 27% of affected cats and only in cats with asymmetric septal thickening. Other histological features of feline HCM include myocardial and endopericardial fibrosis and stenotic coronary arteries. Dynamic aortic outflow occlusion, secondary mitral valve insufficiency, myocardial ischemia, and systemic arterial embolism (SAE) can complicate this syndrome. The left heart is primarily affected, and clinical signs manifest as sudden death, or more commonly, as acute left heart failure due to impaired diastolic function. Pleural exudation is sometimes associated with HCM. Cardiac systolic function is usually adequate or enhanced. Stressful events, such as riding in a car, limitations on ECG, confrontation with a dog, or embolic events, can exacerbate left heart failure and pulmonary edema. Hypertrophic obstructive cardiomyopathy (HOCM) is characterized by left ventricular hypertrophy accompanied by left ventricular outflow obstruction to the aorta. The degree of obstruction and clinical symptoms depends on the extent of the hypertrophy. HOCM most commonly affects the interventricular septum, but any part of the left ventricle can be affected.

[0089] Restrictive cardiomyopathy (RCM) occurs when the diastolic integrity of the ventricle is impaired (i.e., stiffness increases) due to infiltration of the endocardium, subendocardium, or myocardium by fibrous tissue or other components. In contrast to drugs used in humans where specific causes, such as amyloidosis and eosinophilic infiltration, are identified as causes of RCM, there is no clearly defined specific cause for RCM in cats. It is often impossible to distinguish this disorder from idiopathic, unclassifiable cardiomyopathy without using invasive diagnostic procedures that directly measure left ventricular diastolic function, such as DTI, other indirect measurements of diastolic function, or autopsy. The exact cause of RCM in felines is unknown; however, there is some evidence that it may be of an inflammatory nature. Dilated cardiomyopathy (DCM) is characterized by dilation or enlargement of the cardiac ventricles and reduced systolic capacity. Before 1987, DCM was one of the most common heart diseases in cats. DCM is suspected to be related to a dietary deficiency of the amino acid taurine. Currently, DCM in cats is relatively rare, and the link has been further confirmed as most cat food manufacturers have begun adding taurine supplements to these feeds. Some breeds, such as Burmese, Abyssinian, and Siamese, are more commonly affected by DCM, but the underlying cause in the majority of cases remains unknown. The disease usually affects cats between the ages of 2 and 20 years, but the average age of onset is 10 years.

[0090] Unclassifiable cardiomyopathy (UCM): In recent years, there has been an increase in the number of cats identified as not fitting into any recognized disease classification using echocardiography and pathological criteria. Typically, these cats have marked bilateral atrial enlargement, normal or mild left ventricular hypertrophy, and normal or slightly reduced cardiac systolic function, but they do not have fibrosis, which is a typical postmortem finding seen in restrictive cardiomyopathy. Many cats have right ventricular enlargement. It is not known whether these cats represent other known cardiomyopathy conditions in a progressive or degenerative form. Proarrhythmic right ventricular cardiomyopathy (ARVC): This form of cardiomyopathy has recently been described in cats. The cause is unknown, but familial forms have been reported in humans. It is characterized by marked enlargement of the right atrium and right ventricle, and marked tricuspid regurgitation due to distortion of the tricuspid valve. Arrhythmias are common. Cases of ARVC may have been previously misdiagnosed as tricuspid dysplasia.

[0091] In the course of this invention, the term "(primitive mesenchymal) mitral valve disease" [(M)MVD] refers to the most common cardiovascular condition and most frequent cause of (congestive) heart failure in dogs, which fundamentally affects small breed dogs over the age of 5 years. The pathophysiology of (primitive mesenchymal) mitral valve disease is characterized by progressive enlargement of the left ventricle and left atrium resulting from degenerative changes and dysfunction of the mitral valve. Valve defects lead to blood regurgitation and reduced ejection fraction, which presents an additional burden on the heart that causes left ventricular enlargement, and if left untreated, the heart weakens and congestive heart failure (CHF) develops. In the course of this invention, the term “dilated cardiomyopathy” (DCM) in relation to dogs refers to the second most common cardiovascular condition in dogs, affecting large breeds of all ages, with an overall incidence of 8%. DCM is a disease of the cardiomyocytes, presenting itself as enlargement of the left ventricle and left atrium or all ventricles, and often the walls of the heart muscle are much thinner than normal. As a result, the pumping capacity of the ventricles is reduced, blood flow is impaired, and blood stasis occurs. As the disease progresses, this leads to congestive heart failure (CHF).

[0092] In the course of this invention, the term "asymptomatic (latent, preclinical) (primitive mesenchymal) mitral valve disease [(M)MVD]" refers to any cardiac contractile disorder or disease caused by or secondary to (M)MVD, provided that there are no clinical symptoms of (congestive) heart failure. In particular, (M)MVD refers to heart failure resulting from (M)MVD of ISACHC class I (class IA and / or class IB), NYHA class I, and ACVIM stage B2. In the course of this invention, the term "asymptomatic (latent, preclinical) dilated cardiomyopathy (DCM)" refers to any cardiac contractile disorder or disease caused by or secondary to DCM, provided that there are no clinical symptoms of (congestive) heart failure. In particular, DCM refers to heart failure resulting from ISACHC class I DCM. In the course of this invention, the term "one or more SGLT-2 inhibitors in combination with pimobendan or a pharmaceutically acceptable form thereof" refers to a medical combination of two or more active ingredients, i.e., one or more SGLT-2 inhibitors or a pharmaceutically acceptable form thereof administered to a non-human mammal (sick animal) before, after, or concurrently with the administration of pimobendan. In this context, two or more active ingredients may be present in the same dosage form and consequently administered simultaneously. Alternatively, two or more active ingredients may be present in separate (same or different) dosage forms for administration at different time points in succession ("pre-administration" or "post-administration" mode) or for administration at the same time ("concurrent administration" mode).

[0093] SGLT-2 inhibitors for use according to the present invention include, but are not limited to, glucopyranosyl-substituted benzene derivatives, e.g., WO01 / 27128, WO03 / 099836, WO2005 / 092877, WO2006 / 034489, WO2006 / 064033, WO2006 / 117359, WO2006 / 117360, WO2007 / 025 Examples include glucopyranosyl-substituted benzene derivatives described in 943, WO2007 / 028814, WO2007 / 031548, WO2007 / 093610, WO2007 / 128749, WO2008 / 049923, WO2008 / 055870, WO2008 / 055940, WO2009 / 022020, or WO2009 / 022008.

[0094] Furthermore, one or more SGLT-2 inhibitors for use according to the present invention can be selected from the group consisting of the following compounds or their pharmaceutically acceptable forms: (1) Glucopyranosyl-substituted benzene derivative of formula (1) [ka] (In the formula, R 1 represents cyano, Cl, or methyl (most preferably cyano), R 2 represents H, methyl, methoxy, or hydroxy (most preferably H), R 3 This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propane-1-yl, 3-hydroxy- Represents 3-methylbuta-1-yl, 1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethylethyl, 2-methoxyethyl, 2-ethoxyethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxyethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano, R 3 The compound is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy, most preferably R 3 (It is cyclopropyl.) or a derivative thereof, wherein one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -alkyl)carbonyl, (C 1-18-alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 Acylated with a group selected from -alkyl)-carbonyl groups;

[0095] (2) Veragliflozin represented by formula (2): [ka] (3) Dapagliflozin represented by formula (3): [ka]

[0096] (4) Canagliflozin represented by formula (4): [ka] (5) Empagliflozin represented by formula (5): [ka]

[0097] (6) Luseogliflozin represented by formula (6): [ka] (7) Tofogliflozin represented by formula (7): [ka]

[0098] (8) Ipragliflozin represented by formula (8): [ka]

[0099] (9) Erzggliflozin represented by formula (9): [ka]

[0100] (10) Atigliflozin represented by formula (10): [ka]

[0101] (11) Remogliflozin represented by formula (11): [ka]

[0102] (11A) Remogliflozin etabonate represented by formula (11A): [ka]

[0103] (12) Thiofen derivatives of formula (12) [ka] (In the formula, R represents methoxy or trifluoromethoxy);

[0104] (13) 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene represented by formula (13); [ka]

[0105] (14) Spirochetal derivatives of formula (14): [ka] (wherein R represents methoxy, trifluoromethoxy, ethoxy, ethyl, isopropyl, or tert.butyl); (15) Pyrazole-O-glucoside derivatives of formula (15): [ka] (In the formula, R 1 is C 1-3 - Represents alkoxy, L 1 , L 2 These represent H or F independently of each other. R 6 H, (C 1-3 -alkyl)carbonyl, (C 1-6 - Represents alkyl)oxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, or benzylcarbonyl;

[0106] (16) Sotagliflozin represented by formula (16): [ka]

[0107] (17) Cergliflozin represented by formula (17): [ka]

[0108] (18) Compounds represented by formula (18): [ka] (In the formula, R 3This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propane-1-yl, 3-hydroxy- 3-methylbuta-1-yl, 1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethylethyl, 2-methoxyethyl, 2-ethoxyethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxyethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano, R 3 The compound is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy, most preferably R 3 (It is cyclopropyl), or a derivative thereof, wherein one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 Acylated with a group selected from -alkyl)-carbonyl groups;

[0109] (19) Bexagliflozin represented by formula (19): [ka]

[0110] (20) Janagliflozin represented by formula (20): [ka]

[0111] (21) Long liflozin represented by formula (21): [ka] (22) Wampagliflozin; (23) Enabogliflozin represented by formula (23): [ka]

[0112] (24) TFC-039 represented by formula (24): [ka]

[0113] As used herein, the term "bellagliflozin" refers to bellagliflozin of the above structure, as well as its hydrate and solvate, and its crystalline form, including any pharmaceutically acceptable form thereof. Compounds, methods for their synthesis, and cocrystals thereof are described, for example, in WO2007 / 128749, WO2014 / 016381, and WO2019 / 121509. As used herein, the term "dapagliflozin" refers to dapagliflozin having the above structure, as well as its hydrate and solvate, and its crystalline form, including any pharmaceutically acceptable form thereof. The compound and its synthesis method are described, for example, in WO03 / 099836. Preferred hydrates, solvates, and crystalline forms are described, for example, in patent applications WO2008 / 116179 and WO2008 / 002824.

[0114] As used herein, the term "canagliflozin" refers to canagliflozin having the structure described above, as well as its hydrate and solvate, and its crystalline form, including any pharmaceutically acceptable form thereof. Compounds and methods for their synthesis are described, for example, in WO2005 / 012326 and WO2009 / 035969. Preferred hydrates, solvates, and crystalline forms are described, for example, in patent application WO2008 / 069327. The term "empagliflozin," as used herein, refers to empagliflozin having the above structure, as well as its hydrate and solvate, and its pharmaceutically acceptable forms, including its crystalline form. Compounds and methods for their synthesis are described, for example, in WO2005 / 092877, WO2006 / 120208, and WO2011 / 039108. Preferred crystalline forms are described, for example, in patent applications WO2006 / 117359 and WO2011 / 039107. As used herein, the term "atigliflozin" refers to atigliflozin having the structure described above, as well as its hydrate and solvate, and its crystalline form, including any pharmaceutically acceptable form thereof. The compound and its synthesis method are described, for example, in WO2004 / 007517.

[0115] As used herein, the term "ipragliflozin" refers to ipragliflozin having the above structure, as well as its hydrate and solvate, and its crystalline form, including any pharmaceutically acceptable form thereof. Compounds and methods for their synthesis are described, for example, in WO2004 / 080990, WO2005 / 012326 and WO2007 / 114475. As used herein, the term "tofogliflozin" refers to tofogliflozin having the above structure, as well as its hydrate and solvate, and its crystalline form, including any pharmaceutically acceptable form thereof. Compounds and methods for their synthesis are described, for example, in WO2007 / 140191 and WO2008 / 013280. As used herein, the term "luseogliflozin" refers to luseogliflozin having the above-described structure, as well as its hydrate and solvate, and its crystalline form, and any other pharmaceutically acceptable form thereof. As used herein, the term "erzgliflozin" refers to erzgliflozin having the structure described above, as well as its hydrate and solvate, and its crystalline form, including any pharmaceutically acceptable forms thereof. The compound is described, for example, in WO2010 / 023594.

[0116] As used herein, the term "lemogliflozin" refers to the pharmaceutically acceptable forms thereof, including the remogliflozin having the above structure, as well as its prodrugs, particularly remogliflozin etavonate, including its hydrate and solvate, and its crystalline form. Methods for its synthesis are described, for example, in patent applications EP1213296 and EP1354888. As used herein, the term "cergliflozin" refers to cergliflozin having the above-described structure, as well as cergliflozin prodrugs, particularly cergliflozin etavonate, including its hydrates and solvates, and its crystalline forms, and any pharmaceutically acceptable forms thereof. Methods for producing the same are described, for example, in patent applications EP1344780 and EP1489089. The compound of formula (16) above, namely sotagliflozin, and its preparation are described, for example, in WO2008 / 042688 or WO2009 / 014970.

[0117] When used herein, the term "bexagliflozin" refers to bexagliflozin having the above structure, as well as its pharmaceutically acceptable forms, including its hydrate, solvate, and crystalline form. The compound and its synthesis method are described, for example, in WO2009 / 026537. When used herein, the term "TFC-039" refers to the above structure, as well as its pharmaceutically acceptable forms, including its hydrate and solvate and its crystalline form. The compound and its synthesis method are described, for example, in WO2012 / 160218. Preferred SGLT-2 inhibitors are glucopyranosyl-substituted benzene derivatives. Optionally, one or more hydroxyl groups of the glucopyranosyl group are present in such one or more SGLT-2 inhibitors, (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 It may be acylated with a group selected from -alkyl)-carbonyl groups.

[0118] Even more preferred are the glucopyranosyl-substituted benzonitrile derivatives of formula (1) disclosed herein above. However, even more preferred are the glucopyranosyl-substituted benzonitrile derivatives of formula (18): [ka] (In the formula, R 3These include cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methylpropane-1-yl, 3-hydroxy -3-methylbuta-1-yl, 1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethylethyl, 2-methoxyethyl, 2-ethoxyethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxyethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano, R 3 The is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy, R 3 (Most preferably it is cyclopropyl), or a derivative thereof, wherein one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 It is acylated with a group selected from -alkyl)-carbonyl groups.

[0119] Preferably, such an SGLT-2 inhibitor is veragliflozin as shown in formula (2). Optionally, one or more hydroxyl groups of the β-D-glucopyranosyl group of veragliflozin are (C1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 It may be acylated with a group selected from -alkyl)-carbonyl groups.

[0120] Therefore, in preferred embodiments, the at least one SGLT-2 inhibitor according to the present invention is a glucopyranosyl-substituted benzene derivative SGLT-2 inhibitor, preferably an SGLT-2 inhibitor of formula (1), more preferably an SGLT-2 inhibitor of formula (18), or more preferably an SGLT-2 inhibitor of formula (2), i.e., veragliflozin, in any case as defined herein.

[0121] In another preferred embodiment, such an SGLT-2 inhibitor is bexagliflozin shown in formula (19). Optionally, one or more hydroxyl groups of the β-D-glucopyranosyl group of bexagliflozin are (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 It may be acylated with a group selected from -alkyl)-carbonyl groups. Therefore, in another preferred embodiment, at least one SGLT-2 inhibitor according to the present invention is a glucopyranosyl-substituted benzene derivative SGLT-2 inhibitor, preferably an SGLT-2 inhibitor of formula (19), i.e., bexagliflozin, in either case as defined herein above. In this specification, references to SGLT-2 inhibitors and / or their use according to the present invention encompass pharmaceutically acceptable forms of SGLT-2 inhibitors unless otherwise specified. According to the present invention, any pharmaceutically acceptable form of SGLT-2 inhibitor, for example, formula (1), preferably formula (18), and more preferably formula (2), can be used. For example, a crystalline form can be used. A prodrug form is also included in the present invention.

[0122] The prodrug form may include, for example, esters and / or hydrates. The term “prodrug” is also intended to include any covalent carrier that, when administered to a mammalian subject, releases the active compound of the present invention in vivo. Prodrugs of the compounds of the present invention can be prepared by modifying functional groups present in the compounds of the present invention such that the modification is cleaved by a predetermined operation or in vivo to become the parent compound of the present invention.

[0123] The crystalline forms for use according to the present invention include complexes of the SGLT-2 inhibitor with one or more amino acids (see, for example, WO2014 / 016381)—so-called cocrystals. The amino acids for such use may be native amino acids. The amino acids may be proteolytic amino acids (including L-hydroxyproline) or non-proteolytic amino acids. The amino acids may be D-amino acids or L-amino acids. In some preferred embodiments, the amino acid is proline (L-proline and / or D-proline, preferably L-proline). For example, a crystalline complex / cocrystal of veragliflozin with proline (e.g., L-proline) and water of crystallization is preferred. Therefore, crystalline complexes / cocrystals of one or more natural amino acids and SGLT-2 inhibitors are disclosed herein, for example, crystalline complexes / cocrystals of one or more natural amino acids and glucopyranosyl-substituted benzene derivative SGLT-2 inhibitors, preferably SGLT-2 inhibitors of formula (1), more preferably SGLT-2 inhibitors of formula (18), or more preferably SGLT-2 inhibitors of formula (2) (veragliflozin).

[0124] Certain pharmaceutical activity is a fundamental requirement that a pharmaceutically active agent must meet before it is approved as a marketable drug. However, there are various additional requirements that a pharmaceutically active agent must meet. These requirements are based on various parameters, which are related to the properties of the active substance itself. Examples of these parameters, though not limited to them, include the stability of the activator under various environmental conditions, its stability during the production of the pharmaceutical formulation, and the stability of the activator in the final pharmaceutical composition. The pharmaceutically active substance used to prepare the pharmaceutical composition should be as pure as possible, and its stability during long-term storage must be ensured under various environmental conditions. This is essential to prevent the use of pharmaceutical compositions containing, for example, degradation products of the active substance, in addition to the actual active substance. In such cases, the content of the active substance in the pharmaceutical may be less than that specified.

[0125] Uniform distribution of pharmaceuticals in a formulation is a critical factor, especially when the drug must be administered in low doses. To ensure uniform distribution, the particle size of the active substance can be reduced to an appropriate level, for example, by grinding. Although a rigid state is required during the process, degradation of the active pharmaceutical substance as a side effect of grinding (or micronization) must be avoided as much as possible; therefore, it is absolutely essential that the active substance remains extremely stable throughout the grinding process. Only when the active substance is sufficiently stable during the grinding process can a homogeneous pharmaceutical formulation be produced, and a homogeneous pharmaceutical formulation will always contain a specified amount of active substance in a reproducible manner. Another problem that can arise in the grinding process for preparing a desired pharmaceutical formulation is the energy input and stress on the crystal surface caused by this process. In certain circumstances, this can lead to polymorphic, amorphous, or crystalline lattice changes. Since the pharmaceutical quality of a pharmaceutical formulation requires that the active substance always possesses the same crystalline form, the stability and properties of crystalline active substances are also subject to strict requirements from this perspective. The stability of the active pharmaceutical substance is also important in pharmaceutical compositions for determining the shelf life of a particular drug; shelf life is the length of time during which a drug can be administered without any risk. Therefore, high stability of the drug in the above-mentioned pharmaceutical compositions under various storage conditions is an additional advantage for both the patient and the manufacturer.

[0126] Moisture absorption reduces the content of the active pharmaceutical substance due to the increase in mass caused by water uptake. Pharmaceutical compositions that tend to absorb moisture must be protected from moisture during storage, for example, by adding a suitable desiccant or by storing the drug in an environment that protects it from moisture. Therefore, preferably, the active pharmaceutical substance should have at best only slight hygroscopicity. Furthermore, the possibility of obtaining a clearly defined crystalline form allows for the purification of the active pharmaceutical ingredient through recrystallization. Apart from the requirements stated above, it should generally be kept in mind that any change to the solid state of a pharmaceutical composition can improve its physical and chemical stability, providing significant advantages over less stable forms of the same drug. Crystalline complexes / cocrystals of natural amino acids and SGLT-2 inhibitors (e.g., glucopyranosyl-substituted benzene derivatives, or SGLT-2 inhibitors of formula (1) or formula (18), or in particular the SGLT-2 inhibitor of formula (2), i.e., veragliflozin) satisfy the important requirements described earlier herein. SGLT-2 inhibitors or pharmaceutically acceptable forms thereof for use according to the present invention can be prepared as pharmaceutical compositions. These can be prepared as solid or liquid formulations. In either case, they are preferably prepared for oral administration, preferably in liquid form for oral administration (e.g., WO2017 / 032799). However, SGLT-2 inhibitors or pharmaceutically acceptable forms thereof can also be prepared for parenteral administration, for example. Solid formulations include tablets, granular forms, and other solid forms, such as suppositories. Among solid formulations, tablets and granular forms are preferred. Pimobendan for use according to the present invention can be prepared as a pharmaceutical composition. Pimobendan can be prepared as a solid or liquid formulation. In either case, it is preferably prepared for oral administration, preferably in a solid form (tablet) for oral administration (see, for example, WO2005 / 084647 or WO2015 / 082389).

[0127] A pharmaceutical composition in the sense of the present invention may comprise one or more SGLT-2 inhibitors according to the present invention or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, and one or more excipients. Any excipients that enable or support the intended medical effect may be used. Such excipients are available to those skilled in the art. Useful excipients include, for example, anti-sticking agents (used to reduce adhesion between powder (granules) and the punch surface, thereby preventing adhesion to the tablet punch), binders (solution or dry binders that hold components together), coatings (protecting tablet components from degradation due to moisture in the air and making large or unpleasant-tasting tablets easier to swallow), disintegrants (allowing tablet crushing by dilution), fillers, diluents, flavorings, colorants, flow promoters (flow regulators - facilitating powder flow by reducing interparticle friction and adhesion), lubricants (preventing components from clumping together and sticking to the tablet punch or capsule filling machine), preservatives, adsorbents, and sweeteners. The formulations according to the present invention, for example, solid formulations, may contain a carrier and / or disintegrant selected from the group consisting of sugars and sugar alcohols, such as mannitol, lactose, starch, cellulose, microcrystalline cellulose, and cellulose derivatives, such as methylcellulose.

[0128] Manufacturing procedures for formulations suitable for canids are known to those skilled in the art and include, for example, direct compression, dry granulation, and wet granulation for solid formulations. In the direct compression process, the active ingredient and all other excipients are placed together in a compression device, and the device is applied directly to press the material to obtain tablets. The resulting tablets may then be coated and / or chemically protected, for example, with materials known from the latest technology.

[0129] For example, a unit for administration, such as a single liquid dose, or a unit of a solid formulation, such as a tablet, may contain 0.1 mg to 10 mg, or for example, 0.3 mg to 1 mg, 1 mg to 3 mg, 3 mg to 10 mg; or 5 to 2500 mg, or for example, 5 to 2000 mg, 5 mg to 1500 mg, 10 mg to 1500 mg, 10 mg to 1000 mg, or 10 to 500 mg of an SGLT-2 inhibitor, and 0.1 mg to 10 mg of pimobendan, or for example, 1.25 mg, 2.5 mg, 5 mg, or 10 mg of pimobendan. As those skilled in the art will understand, the content of SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in solid formulations, as well as pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof, or any formulations disclosed herein for administration to non-human mammals, can be increased or decreased as needed in proportion to the body weight of the non-human mammal to be treated. In one embodiment, the pharmaceutical composition for use according to the present invention is designed for oral or parenteral administration, preferably for oral administration. Oral administration in particular is improved by excipients, which modify the odor and / or tactile properties of the pharmaceutical composition for the intended patient, as described, for example.

[0130] When a GLT-2 inhibitor or a pharmaceutically acceptable form thereof, combined with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, is formulated for oral administration for use according to the present invention, it is preferable that the excipients impart properties such as palatability and / or chewiness that result in a formulation suitable for administration to non-human mammals.

[0131] Liquid formulations are also preferred. Liquid formulations may be, for example, liquids, syrups, or suspensions. These may be administered directly to non-human mammals or mixed with the feed and / or beverages (e.g., drinking water) of non-human mammals. One advantage of liquid formulations (similar to granular formulations) is that such dosage forms allow for precise administration. For example, SGLT-2 inhibitors or their pharmaceutically acceptable forms and pimobendan and / or telmisartan or their pharmaceutically acceptable forms can be administered precisely in proportion to the body mass of non-human mammals. Typical compositions of liquid formulations are known to those skilled in the art.

[0132] According to the present invention, two or more pharmaceutically active substances can be combined into a single dosage form, i.e., a combination drug. The advantage of such a formulation is that the dose is fixed in this pharmaceutical formulation, i.e., it is available in a specific fixed dose. In such cases, the pharmaceutical formulation is called a "fixed-dose combination" (FDC) and can be either a solid or liquid formulation. In another embodiment, the pharmaceutical composition for use according to the present invention is a fixed-dose combination (FDC) of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof, preferably such FDC is a solid or liquid formulation.

[0133] In a preferred embodiment, the FDC comprises veragliflozin or a pharmaceutically acceptable form thereof and pimobendan as the sole pharmaceutically active substance. In another embodiment, the FDC comprises veragliflozin or a pharmaceutically acceptable form thereof, pimobendan, and telmisartan or a pharmaceutically acceptable form thereof as the sole pharmaceutically active substance. In yet another embodiment, the FDC comprises veragliflozin or a pharmaceutically acceptable form thereof and telmisartan or a pharmaceutically acceptable form thereof as the sole pharmaceutically active substance. In another preferred embodiment, the FDC comprises bexagliflozin or a pharmaceutically acceptable form thereof and pimobendan as the sole pharmaceutically active substance. In another embodiment, the FDC comprises bexagliflozin or a pharmaceutically acceptable form thereof, pimobendan, and telmisartan or a pharmaceutically acceptable form thereof as the sole pharmaceutically active substance. In another embodiment, the FDC comprises bexagliflozin or a pharmaceutically acceptable form thereof and telmisartan or a pharmaceutically acceptable form thereof as the sole pharmaceutically active substance.

[0134] A physician skilled in the art can determine a suitable dosage for use of the present invention. A preferred unit of administration is mg / kg body weight, i.e., SGLT-2 inhibitor per body mass of a non-human mammal (unit: mg). The SGLT-2 inhibitor of the present invention may be administered in doses such as 0.01 to 10 mg / kg body weight per day, 0.01 to 5 mg / kg body weight per day, 0.01 to 4 mg / kg body weight per day, 0.01 to 3 mg / kg body weight per day, 0.01 to 2 mg / kg body weight per day, 0.01 to 1.5 mg / kg body weight per day, 0.01 to 1 mg / kg body weight per day, 0.01 to 0.75 mg / kg body weight per day, 0.01 to 0.5 mg / kg body weight per day, or 0.01 to 0.4 mg / kg body weight per day; or 0.1 to 3.0 mg / kg body weight per day, preferably 0.2 to 2.0 mg / kg body weight per day, more preferably 0.1 to 1 mg / kg body weight per day, or 0.5 to 1 mg / kg body weight per day. In another preferred embodiment, the dose is 0.01 to 1 mg / kg body weight per day, preferably 0.01 to 0.5 mg / kg body weight per day, more preferably 0.02 to 0.4 mg / kg body weight per day, for example, 0.03 to 0.3 mg / kg body weight per day. Alternatively, the SGLT-2 inhibitor of the present invention may be administered in doses such as 0.1 to 10 mg / kg body weight per day, 0.1 to 5 mg / kg body weight per day, 0.1 to 4 mg / kg body weight per day, 0.1 to 3 mg / kg body weight per day, 0.1 to 2 mg / kg body weight per day, 0.1 to 1.5 mg / kg body weight per day, 0.1 to 1 mg / kg body weight per day, 0.1 to 0.75 mg / kg body weight per day, 0.1 to 0.5 mg / kg body weight per day, or 0.1 to 0.4 mg / kg body weight per day. A physician skilled in the art can prepare the SGLT-2 inhibitor of the present invention for administration at a desired dose.

[0135] With respect to pimobendan, a physician skilled in the art can determine a suitable dose for use in the present invention. A preferred unit of administration is mg / kg body weight, i.e., the amount of pimobendan per body mass of a non-human mammal (unit: mg). Pimobendan may be administered in doses of, for example, 0.1 to 1 mg / kg body weight per day, for example, 0.2 to 0.6 mg / kg body weight per day, for example, 0.5 mg / kg body weight per day. A skilled physician in this field can prepare pimobendan for administration at the desired dose.

[0136] With respect to telmisartan or its pharmaceutically acceptable forms, a physician skilled in the art can determine a suitable dose for use in the present invention. A preferred unit of administration is mg / kg body weight, i.e., the amount of telmisartan per body mass of a non-human mammal (unit: mg). Telmisartan or its pharmaceutically acceptable forms may be administered, for example, in doses of 0.01 to 10 mg / kg body weight per day, preferably 0.05 to 8 mg / kg body weight, more preferably 0.1 to 5 mg / kg body weight, more preferably 0.2 to 4 mg / kg body weight, more preferably 0.3 to 3 mg / kg body weight, more preferably 0.4 to 2.5 mg / kg body weight, more preferably 0.5 to 2 mg / kg body weight, most preferably 0.75 to 1.5 mg / kg body weight per day, or in doses of, for example, 1.25 mg, 2.5 mg, 5 mg, or 10 mg per day. A skilled physician in the art can prepare telmisartan or a pharmaceutically acceptable form thereof for administration at a desired dose. [Examples]

[0137] The following examples serve to further illustrate the present invention, but should not be construed as limiting the scope of the invention as disclosed herein.

[0138] (Example 1) A field trial to evaluate the monotherapy of velagliflozin administered orally once a day and pimobendan administered orally twice a day, as well as their combination therapy, in dogs with DCM (different disease stages after B1). Dogs are randomly selected for velagliflozin, or pimobendan, or either velagliflozin and pimobendan. During the experimental period, the dogs are evaluated regularly, which includes a comprehensive physical examination, including body weight, body condition score, blood pressure, and auscultation of the cardiovascular system (e.g., abnormalities such as heart rate, rhythm, strength, heart murmur, etc.), chest radiography (lateral-lateral, dorsoventral), echocardiography, ECG, blood tests [chemical tests, complete blood count (CBC), cardiac biomarkers, ketone bodies], and urine tests. The following parameters are evaluated: · Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, reduced exercise tolerance, anorexia, syncope, abdominal distension, and polydipsia) · Echocardiography parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of effusion) · ECG evaluation (optional) · Time to event (death or hospitalization due to heart failure) · Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) · Reduction in the dose of diuretic therapy (e.g., furosemide, torsemide) · Initiation of additional treatment for heart disease (e.g., pimobendan, ACE inhibitor) · Blood parameters (e.g., NTproBNP, troponin) · Quality of life (evaluation by the owner) · Evaluation by the investigator regarding treatment effect / disease control · Respiratory rate at rest · X-ray examination (heart size and pulmonary edema, congestion) · Disease progression (progression to the next stage) · Systolic blood pressure (SBP) · NYHA classification / ACVIM classification.

[0139] The results of the clinical field trial show that the combination therapy demonstrates a significant and clinically important extension of survival time and time to event (the event was defined as cardiac death / euthanasia and (re)occurrence of congestive heart failure) compared to treatment with either empagliflozin or pimobendan. Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), cardiac echo parameters, and cardiac biomarkers also show a higher degree of improvement compared to monotherapy.

[0140] (Example 2) A field trial to evaluate empagliflozin as additional therapy to pimobendan compared to placebo as additional therapy to pimobendan in dogs with DCM (different disease stages from B1 onwards) Dogs are randomly assigned to either placebo and pimobendan or either empagliflozin and pimobendan. During the experimental period, the dogs are evaluated regularly, which includes a comprehensive physical examination including body weight, body condition score, blood pressure, and auscultation of the cardiovascular system (e.g., abnormalities such as heart rate, rhythm, strength, heart murmur, etc.), chest radiography (lateral - lateral, dorsoventral), echocardiography, ECG, blood tests (chemical tests, CBC, cardiac biomarkers, ketone bodies), and urine tests.

[0141] The following parameters are evaluated: · Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, reduced exercise tolerance, anorexia, syncope, abdominal distension, and polydipsia) · Echocardiography parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of effusion) · ECG evaluation (optional) · Time to event (death or hospitalization due to heart failure) · Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) · Reduction in the dose of diuretic therapy (e.g., furosemide, torsemide) · Initiation of additional therapy for heart disease (e.g., pimobendan, ACE inhibitor) • Blood parameters (e.g., NTproBNP, troponin) • Quality of life (evaluated by the owner) • Evaluation by the trial personnel regarding treatment efficacy / disease control ·Resting breathing rate • X-ray examination (heart size, pulmonary edema, congestion) • Disease progression (progression to the next stage) • Cardiac systolic blood pressure (SBP) ·NYHA classification / ACVIM classification. Results from clinical field trials show that the combination of veragliflozin and pimobendan demonstrates a significant, clinically important extension of survival time and time to events (events defined as cardiac death / euthanasia and (re)onset of congestive heart failure) compared to placebo on pimobendan alone. Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), echocardiographic parameters, and cardiac biomarkers also show a greater degree of improvement compared to monotherapy.

[0142] (Example 3) A field study evaluating monotherapy with veragliflozin administered orally once daily and telmisartan administered orally once daily, as well as combination therapy with these, in dogs with DCM (different disease stages from B1 onwards). Dogs will be randomly selected to receive either veragliflozin, telmisartan, or both. Throughout the experiment, dogs will be regularly evaluated, including a comprehensive physical examination including weight, body condition score, blood pressure, and auscultation of the cardiovascular system (e.g., abnormalities such as heart rate, rhythm, strength, and heart murmurs), chest X-rays (lateral and ventricular, dorsal and ventral), echocardiography, ECG, blood tests (chemical tests, CBC, cardiac biomarkers, ketones), and urinalysis.

[0143] The following parameters are evaluated: • Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension, and polydipsia) • Echocardiography parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of exudate) • ECG evaluation (optional) • Time until the event (death or hospitalization due to heart failure) • Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) • Dose reduction of diuretic therapy (e.g., furosemide, torasemide) • Initiation of additional treatment for heart disease (e.g., pimobendan, ACE inhibitors) • Blood parameters (e.g., NTproBNP, troponin) • Quality of life (evaluated by the owner) • Evaluation by the trial personnel regarding treatment efficacy / disease control ·Resting breathing rate • X-ray examination (heart size, pulmonary edema, congestion) • Disease progression (progression to the next stage) • Cardiac systolic blood pressure (SBP) ·NYHA classification / ACVIM classification.

[0144] Results from clinical field trials show that combination therapy significantly extends clinically important survival and time to events (defined as cardiac death / euthanasia and (re)recurrence of congestive heart failure), prevents and improves hypertension, compared to treatment with either veragliflozin or telmisartan alone. Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), echocardiographic parameters, and cardiac biomarkers also show a greater degree of improvement compared to monotherapy.

[0145] (Example 4) A field study evaluating veragliflozin as an add-on therapy to telmisartan compared to placebo in dogs with dilated cardiomyopathy (DCM) (different disease stages from B1 onwards). Dogs are randomly assigned to either placebo and telmisartan or vericiguat and telmisartan. During the experimental period, the dogs are evaluated regularly, which includes a comprehensive physical examination, including body weight, body condition score, blood pressure, and auscultation of the cardiovascular system (e.g., abnormalities such as heart rate, rhythm, strength, heart murmur, etc.), chest X-ray (lateral - lateral, dorsoventral), echocardiogram, ECG, blood tests (chemical tests, CBC, cardiac biomarkers, ketone bodies), and urine tests.

[0146] The following parameters are evaluated: · Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, reduced exercise tolerance, anorexia, syncope, abdominal distension, and polydipsia) · Echocardiogram parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of effusion) · ECG evaluation (optional) · Time to event (death or hospitalization due to heart failure) · Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) · Reduction in the dose of diuretic treatment (e.g., furosemide, torsemide) · Initiation of additional treatment for heart disease (e.g., pimobendan, ACE inhibitor) · Blood parameters (e.g., NTproBNP, troponin) · Quality of life (evaluated by the owner) · Evaluation by the investigator regarding treatment effect / disease control · Respiratory rate at rest · X-ray examination (heart size and pulmonary edema, congestion) · Disease progression (progression to the next stage) · Systolic blood pressure (SBP) · NYHA classification / ACVIM classification.

[0147] Results from clinical field trials show that the combination of veragliflozin and telmisartan significantly extends clinically important survival and time to events (defined as cardiac death / euthanasia and (re)onset of congestive heart failure), and prevents and improves hypertension compared to placebo on telmisartan alone. Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), echocardiographic parameters, and cardiac biomarkers also show a greater degree of improvement compared to monotherapy.

[0148] (Example 5) Field study to evaluate monotherapy with veragliflozin administered orally once daily and pimobendan administered orally twice daily, as well as combination therapy with these therapies, in dogs with MVD (different disease stages from B1 onwards). Dogs will be randomly selected to receive either veragliflozin, pimobendan, or both. Throughout the experiment, dogs will be regularly evaluated, including a comprehensive physical examination including weight, body condition score, blood pressure, and auscultation of the cardiovascular system (e.g., abnormalities such as heart rate, rhythm, strength, and heart murmurs), chest X-rays (lateral and ventricular, dorsal and ventral), echocardiography, ECG, blood tests (chemical tests, CBC, cardiac biomarkers, ketones), and urinalysis.

[0149] The following parameters are evaluated: • Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension, and polydipsia) • Echocardiography parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of exudate) • ECG evaluation (optional) • Time until the event (death or hospitalization due to heart failure) • Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) • Dose reduction of diuretic therapy (e.g., furosemide, torasemide) • Initiation of additional treatment for heart disease (e.g., pimobendan, ACE inhibitors) • Blood parameters (e.g., NTproBNP, troponin) • Quality of life (evaluated by the owner) • Evaluation by the trial personnel regarding treatment efficacy / disease control ·Resting breathing rate • X-ray examination (heart size, pulmonary edema, congestion) • Disease progression (progression to the next stage) • Cardiac systolic blood pressure (SBP) ·NYHA classification / ACVIM classification.

[0150] Results from clinical field trials show that combination therapy significantly extends clinically important survival and time to events (defined as cardiac death / euthanasia and (re)recurrence of congestive heart failure) compared to treatment with either veragliflozin or pimobendan alone. Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), echocardiographic parameters, and cardiac biomarkers also show a greater degree of improvement compared to monotherapy.

[0151] (Example 6) A field trial to evaluate veragliflozin as an add-on therapy to pimobendan compared to placebo in dogs with MVD (different disease stages from B1 onwards). Dogs will be randomly selected to receive either placebo or pimobendan, or veragliflozin or pimobendan. Throughout the experiment, dogs will be regularly evaluated, including a comprehensive physical examination including weight, body condition score, blood pressure, and auscultation of the cardiovascular system (e.g., abnormalities such as heart rate, rhythm, strength, and heart murmurs), chest X-rays (lateral and ventricular), echocardiography, ECG, blood tests (chemical tests, CBC, cardiac biomarkers, ketones), and urinalysis.

[0152] The following parameters are evaluated: • Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension, and polydipsia) • Echocardiography parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of exudate) • ECG evaluation (optional) • Time until the event (death or hospitalization due to heart failure) • Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) • Dose reduction of diuretic therapy (e.g., furosemide, torasemide) • Initiation of additional treatment for heart disease (e.g., pimobendan, ACE inhibitors) • Blood parameters (e.g., NTproBNP, troponin) • Quality of life (evaluated by the owner) • Evaluation by the trial personnel regarding treatment efficacy / disease control ·Resting breathing rate • X-ray examination (heart size, pulmonary edema, congestion) • Disease progression (progression to the next stage) • Cardiac systolic blood pressure (SBP) ·NYHA classification / ACVIM classification. Results from clinical field trials show that the combination of veragliflozin and pimobendan demonstrates a significant, clinically important extension of survival time and time to events (events defined as cardiac death / euthanasia and (re)onset of congestive heart failure) compared to placebo on pimobendan alone. Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), echocardiographic parameters, and cardiac biomarkers also show a greater degree of improvement compared to monotherapy.

[0153] (Example 7) A field study evaluating monotherapy with veragliflozin administered orally once daily and telmisartan administered orally once daily, as well as combination therapy with these, in dogs with MVD (different disease stages from B1 onwards). Dogs will be randomly selected to receive either veragliflozin, telmisartan, or both. Throughout the experiment, dogs will be regularly evaluated, including a comprehensive physical examination including weight, body condition score, blood pressure, and auscultation of the cardiovascular system (e.g., abnormalities such as heart rate, rhythm, strength, and heart murmurs), chest X-rays (lateral and ventricular, dorsal and ventral), echocardiography, ECG, blood tests (chemical tests, CBC, cardiac biomarkers, ketones), and urinalysis.

[0154] The following parameters are evaluated: • Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension, and polydipsia) • Echocardiography parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of exudate) • ECG evaluation (optional) • Time until the event (death or hospitalization due to heart failure) • Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) • Dose reduction of diuretic therapy (e.g., furosemide, torasemide) • Initiation of additional treatment for heart disease (e.g., pimobendan, ACE inhibitors) • Blood parameters (e.g., NTproBNP, troponin) • Quality of life (evaluated by the owner) • Evaluation by the trial personnel regarding treatment efficacy / disease control ·Resting breathing rate • X-ray examination (heart size, pulmonary edema, congestion) • Disease progression (progression to the next stage) • Cardiac systolic blood pressure (SBP) ·NYHA classification / ACVIM classification.

[0155] Results from clinical field trials show that combination therapy significantly extends clinically important survival and time to events (defined as cardiac death / euthanasia and (re)recurrence of congestive heart failure), prevents hypertension, and improves hypertension compared to treatment with either veragliflozin or telmisartan alone. Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), echocardiographic parameters, and cardiac biomarkers also show a greater degree of improvement compared to monotherapy.

[0156] (Example 8) A field trial to evaluate veragliflozin as an add-on therapy to telmisartan compared to placebo in dogs with MVD (different disease stages from B1 onwards). Dogs will be randomly selected to receive either placebo or telmisartan, or veragliflozin or telmisartan. Throughout the experiment, dogs will be regularly evaluated, including a comprehensive physical examination including weight, body condition score, blood pressure, and auscultation of the cardiovascular system (e.g., abnormalities such as heart rate, rhythm, strength, and heart murmurs), chest X-rays (lateral and ventricular, dorsal and ventral), echocardiography, ECG, blood tests (chemical tests, CBC, cardiac biomarkers, ketones), and urinalysis.

[0157] The following parameters are evaluated: • Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension, and polydipsia) • Echocardiography parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of exudate) • ECG evaluation (optional) • Time until the event (death or hospitalization due to heart failure) • Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) • Dose reduction of diuretic therapy (e.g., furosemide, torasemide) • Initiation of additional treatment for heart disease (e.g., pimobendan, ACE inhibitors) • Blood parameters (e.g., NTproBNP, troponin) • Quality of life (evaluated by the owner) • Evaluation by the trial personnel regarding treatment efficacy / disease control ·Resting breathing rate • X-ray examination (heart size, pulmonary edema, congestion) • Disease progression (progression to the next stage) • Cardiac systolic blood pressure (SBP) ·NYHA classification / ACVIM classification.

[0158] Results from clinical field trials show that the combination of veragliflozin and telmisartan significantly extends clinically important survival and time to events (defined as cardiac death / euthanasia and (re)onset of congestive heart failure), and prevents and improves hypertension compared to placebo on telmisartan alone. Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), echocardiographic parameters, and cardiac biomarkers also show a greater degree of improvement compared to monotherapy.

[0159] (Example 9) A field study evaluating monotherapy with veragliflozin administered orally once daily and pimobendan administered orally twice daily, as well as combination therapy, in cats with HCM (different disease stages from B1 onwards). Cats will be randomly selected to receive either veragliflozin, pimobendan, or both. During the experiment, cats will be regularly evaluated, including a comprehensive physical examination including weight, body condition score, blood pressure, and auscultation of the cardiovascular system (e.g., abnormalities such as heart rate, rhythm, strength, and heart murmurs), chest X-rays (lateral and ventricular, dorsal and ventral), echocardiography, ECG, blood tests (chemical tests, CBC, cardiac biomarkers, ketones), and urinalysis.

[0160] The following parameters are evaluated: • Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension, and polydipsia) • Echocardiography parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of exudate) • ECG evaluation (optional) • Time until the event (death or hospitalization due to heart failure) • Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) • Dose reduction of diuretic therapy (e.g., furosemide, torasemide) • Initiation of additional treatment for heart disease (e.g., pimobendan, ACE inhibitors) • Blood parameters (e.g., NTproBNP, troponin) • Quality of life (evaluated by the owner) • Evaluation by the trial personnel regarding treatment efficacy / disease control ·Resting breathing rate • X-ray examination (heart size, pulmonary edema, congestion) • Disease progression (progression to the next stage) • Cardiac systolic blood pressure (SBP) ·NYHA classification / ACVIM classification. Results from clinical field trials show that combination therapy, compared to treatment with either veragliflozin or pimobendan, demonstrates a significant, clinically important extension of survival time and time to events (defined as cardiac death / euthanasia and (re)recurrence of congestive heart failure). Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), echocardiographic parameters, and cardiac biomarkers also show a greater degree of improvement compared to monotherapy.

[0161] (Example 10) A field trial evaluating veragliflozin as an add-on therapy to pimobendan compared to placebo in cats with HCM (different disease stages from B1 onwards). Cats will be randomly selected to receive either placebo or pimobendan, or veragliflozin or pimobendan. Throughout the experiment, cats will be regularly evaluated, including a comprehensive physical examination including weight, body condition score, blood pressure, and auscultation of the cardiovascular system (e.g., abnormalities such as heart rate, rhythm, strength, and heart murmurs), chest X-rays (lateral and ventricular), echocardiography, ECG, blood tests (chemical tests, CBC, cardiac biomarkers, ketones), and urinalysis.

[0162] The following parameters are evaluated: • Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension, and polydipsia) • Echocardiography parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of exudate) • ECG evaluation (optional) • Time until the event (death or hospitalization due to heart failure) • Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) • Dose reduction of diuretic therapy (e.g., furosemide, torasemide) • Initiation of additional treatment for heart disease (e.g., pimobendan, ACE inhibitors) • Blood parameters (e.g., NTproBNP, troponin) • Quality of life (evaluated by the owner) • Evaluation by the trial personnel regarding treatment efficacy / disease control ·Resting breathing rate • X-ray examination (heart size, pulmonary edema, congestion) • Disease progression (progression to the next stage) • Cardiac systolic blood pressure (SBP) ·NYHA classification / ACVIM classification.

[0163] Results from clinical field trials show that the combination of veragliflozin and pimobendan demonstrates a significant, clinically important extension of survival time and time to events (events defined as cardiac death / euthanasia and (re)onset of congestive heart failure) compared to placebo on pimobendan alone. Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), echocardiographic parameters, and cardiac biomarkers also show a greater degree of improvement compared to monotherapy.

[0164] (Example 11) A field study evaluating monotherapy with veragliflozin administered orally once daily and telmisartan administered orally once daily, as well as combination therapy with these, in cats with HCM (different disease stages from B1 onwards). Cats will be randomly selected to receive either veragliflozin, telmisartan, or both. Throughout the experiment, cats will be regularly evaluated, including a comprehensive physical examination including weight, body condition score, blood pressure, and auscultation of the cardiovascular system (e.g., abnormalities in heart rate, rhythm, strength, and murmurs), chest X-rays (lateral and ventricular), echocardiography, ECG, blood tests (chemical tests, CBC, cardiac biomarkers, ketones), and urinalysis.

[0165] The following parameters are evaluated: • Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension, and polydipsia) • Echocardiography parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of exudate) • ECG evaluation (optional) • Time until the event (death or hospitalization due to heart failure) • Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) • Dose reduction of diuretic therapy (e.g., furosemide, torasemide) • Initiation of additional treatment for heart disease (e.g., pimobendan, ACE inhibitors) • Blood parameters (e.g., NTproBNP, troponin) • Quality of life (evaluated by the owner) • Evaluation by the trial personnel regarding treatment efficacy / disease control ·Resting breathing rate • X-ray examination (heart size, pulmonary edema, congestion) • Disease progression (progression to the next stage) • Cardiac systolic blood pressure (SBP) ·NYHA classification / ACVIM classification.

[0166] Results from clinical field trials show that combination therapy significantly extends clinically important survival and time to events (defined as cardiac death / euthanasia and (re)recurrence of congestive heart failure), prevents hypertension, and improves hypertension compared to treatment with either veragliflozin or telmisartan alone. Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), echocardiographic parameters, and cardiac biomarkers also show a greater degree of improvement compared to monotherapy.

[0167] (Example 12) A field study evaluating veragliflozin as an add-on therapy to pimobendan compared to placebo as an add-on therapy to telmisartan in cats with HCM (different disease stages from B1 onwards). Cats will be randomly selected to receive either placebo or telmisartan, or veragliflozin and telmisartan. Throughout the experiment, cats will be regularly evaluated, including a comprehensive physical examination including weight, body condition score, blood pressure, and auscultation of the cardiovascular system (e.g., abnormalities such as heart rate, rhythm, strength, and heart murmurs), chest X-rays (lateral and ventricular, dorsal and ventral), echocardiography, ECG, blood tests (chemical tests, CBC, cardiac biomarkers, ketones), and urinalysis.

[0168] The following parameters are evaluated: • Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension, and polydipsia) • Echocardiography parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of exudate) • ECG evaluation (optional) • Time until the event (death or hospitalization due to heart failure) • Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) • Dose reduction of diuretic therapy (e.g., furosemide, torasemide) • Initiation of additional treatment for heart disease (e.g., pimobendan, ACE inhibitors) • Blood parameters (e.g., NTproBNP, troponin) • Quality of life (evaluated by the owner) • Evaluation by the trial personnel regarding treatment efficacy / disease control ·Resting breathing rate • X-ray examination (heart size, pulmonary edema, congestion) • Disease progression (progression to the next stage) • Cardiac systolic blood pressure (SBP) ·NYHA classification / ACVIM classification.

[0169] Results from clinical field trials show that the combination of veragliflozin and telmisartan significantly extends clinically important survival and time to events (defined as cardiac death / euthanasia and (re)onset of congestive heart failure), and prevents and improves hypertension compared to placebo on telmisartan alone. Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), echocardiographic parameters, and cardiac biomarkers also show a greater degree of improvement compared to monotherapy.

[0170] (Example 13) A field study evaluating the combination therapy of veragliflozin, telmisartan, and pimobendan in dogs with DCM (different disease stages from B1 onwards). Dogs will be randomly selected to receive either veragliflozin, telmisartan, or pimobendan, or veragliflozin, telmisartan, or pimobendan. Throughout the experiment, dogs will be regularly evaluated, including a comprehensive physical examination with weight, body condition score, blood pressure, and cardiovascular auscultation (e.g., abnormalities such as heart rate, rhythm, strength, and heart murmurs), chest X-rays (lateral and ventricular, dorsal and ventral), echocardiography, ECG, blood tests (chemical tests, CBC, cardiac biomarkers, ketones), and urinalysis.

[0171] The following parameters are evaluated: - Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension, and polydipsia) - Echocardiography parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of exudate) - ECG evaluation (optional) - Time until the event (death or hospitalization due to heart failure) - Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) - Dose reduction of diuretic therapy (e.g., furosemide, torasemide) - Initiation of additional treatment for heart disease (e.g., pimobendan, ACE inhibitors) - Blood parameters (e.g., NTproBNP, troponin) - Quality of life (evaluated by the owner) - Evaluation by the trial investigator regarding treatment efficacy / disease control - Resting respiratory rate - X-ray examination (heart size, pulmonary edema, congestion) - Disease progression (advancement to the next stage of the disease) - Cardiac systolic blood pressure (SBP) - NYHA classification / ACVIM classification.

[0172] Results from clinical field trials show that the combination of veragliflozin, telmisartan, and pimobendan significantly extends clinically important survival and time to events (defined as cardiac death / euthanasia and (re)recurrence of congestive heart failure), prevents and improves hypertension, compared to monotherapy. Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), echocardiographic parameters, and cardiac biomarkers also show a greater degree of improvement compared to monotherapy.

[0173] (Example 14) A field study evaluating the combination therapy of veragliflozin, telmisartan, and pimobendan in dogs with MVD (different disease stages from B1 onwards). Dogs will be randomly selected to receive either veragliflozin, telmisartan, or pimobendan, or veragliflozin, telmisartan, or pimobendan. Throughout the experiment, dogs will be regularly evaluated, including a comprehensive physical examination with weight, body condition score, blood pressure, and auscultation of the cardiovascular system (e.g., abnormalities such as heart rate, rhythm, strength, and heart murmurs), chest X-rays (lateral and ventricular, dorsal and ventral), echocardiography, ECG, blood tests (chemical tests, CBC, cardiac biomarkers, ketones), and urinalysis.

[0174] The following parameters are evaluated: - Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension, and polydipsia) - Echocardiography parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of exudate) - ECG evaluation (optional) - Time until the event (death or hospitalization due to heart failure) - Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) - Dose reduction of diuretic therapy (e.g., furosemide, torasemide) - Initiation of additional treatment for heart disease (e.g., pimobendan, ACE inhibitors) - Blood parameters (e.g., NTproBNP, troponin) - Quality of life (evaluated by the owner) - Evaluation by the trial investigator regarding treatment efficacy / disease control - Resting respiratory rate - X-ray examination (heart size, pulmonary edema, congestion) - Disease progression (advancement to the next stage of the disease) - Cardiac systolic blood pressure (SBP) - NYHA classification / ACVIM classification.

[0175] Results from clinical field trials show that the combination of veragliflozin, telmisartan, and pimobendan significantly extends clinically important survival and time to events (defined as cardiac death / euthanasia and (re)recurrence of congestive heart failure), prevents and improves hypertension, compared to monotherapy. Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), echocardiographic parameters, and cardiac biomarkers also show a greater degree of improvement compared to monotherapy.

[0176] (Example 15) A field study evaluating the combination therapy of veragliflozin, telmisartan, and pimobendan in cats with HCM (different disease stages from B1 onwards). Cats will be randomly selected to receive either veragliflozin, telmisartan, pimobendan, or veragliflozin, telmisartan, or pimobendan. Throughout the experiment, cats will be regularly evaluated, including a comprehensive physical examination with weight, body condition score, blood pressure, and auscultation of the cardiovascular system (e.g., abnormalities such as heart rate, rhythm, strength, and heart murmurs), chest X-rays (lateral and ventricular, dorsal and ventral), echocardiography, ECG, blood tests (chemical tests, CBC, cardiac biomarkers, ketones), and urinalysis.

[0177] The following parameters are evaluated: - Clinical signs (e.g., shortness of breath, dyspnea, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension, and polydipsia) - Echocardiography parameters (e.g., IVSd, LA diameter, Ao diameter, LVIDd, LVWd, LVWs, IVSd, LVPWd, EDV, ESV, EF, %FS, presence of exudate) - ECG evaluation (optional) - Time until the event (death or hospitalization due to heart failure) - Number of events (death or hospitalization due to heart failure, congestive heart failure (pulmonary edema)) - Dose reduction of diuretic therapy (e.g., furosemide, torasemide) - Initiation of additional treatment for heart disease (e.g., pimobendan, ACE inhibitors) - Blood parameters (e.g., NTproBNP, troponin) - Quality of life (evaluated by the owner) - Evaluation by the trial investigator regarding treatment efficacy / disease control - Resting respiratory rate - X-ray examination (heart size, pulmonary edema, congestion) - Disease progression (advancement to the next stage of the disease) - Cardiac systolic blood pressure (SBP) - NYHA classification / ACVIM classification.

[0178] Results from clinical field trials show that the combination of veragliflozin, telmisartan, and pimobendan significantly extends clinically important survival and time to events (defined as cardiac death / euthanasia and (re)recurrence of congestive heart failure), prevents and improves hypertension, compared to monotherapy. Furthermore, clinical parameters (e.g., appetite, activity level, and respiration), echocardiographic parameters, and cardiac biomarkers also show a greater degree of improvement compared to monotherapy.

[0179] (Example 16) Further field testing A field study evaluating the combination therapy of veragliflozin administered orally once daily and pimobendan administered orally twice daily in dogs with dilated cardiomyopathy (DCM). The described study is a prospective, baseline-controlled, open-label, multicenter exploratory clinical field trial. Owner-owned dogs diagnosed with DCM are randomly selected to receive either pimobendan or veragliflozin and pimobendan. Two dogs were successfully enrolled. The clinical field trial is currently ongoing. As part of the experiment, registered dogs will be regularly evaluated, including a comprehensive health checkup including weight, blood pressure, and auscultation of the cardiovascular system, chest X-rays to assess heart size, pulmonary edema, and congestion, standard echocardiography, ECG, blood tests, and urinalysis. Cardiovascular history is assessed by reviewing the date of diagnosis of DCM and whether there is a history of heart failure. Owner questionnaires are regularly collected to provide an overview of the dog's overall condition, resting respiratory rate, and exercise tolerance over the past seven days of treatment.

[0180] The dogs included must have been diagnosed with DCM stage B2 or stage C via health examination and echocardiography. The variables to be considered are clinical symptoms, echocardiographic parameters, blood or urine parameters, blood pressure, number of events (death, hospitalization due to heart failure, or euthanasia), time to event, adjustment of diuretic therapy, owner questionnaire data, X-ray results, and disease progression (progression to the next stage, need for additional or prohibited cardiac treatment). During the ongoing field trial, one dog has successfully reached the 90-day ± 5-day evaluation visit. This dog has been classified as having stage C / clinical DCM and is receiving veragliflozin (0.5 mg / kg body weight orally once daily), furosemide (1 mg / kg body weight twice daily), and pimobendan (0.5 mg / kg body weight daily, administered orally in two unequal doses).

[0181] The evaluation results confirmed a positive therapeutic effect. Cardiac systolic blood pressure decreased from 163 mmHg (screening) to 121 mmHg (day 42) and 144 mmHg (day 98). In addition, the heart murmur improved from grade 4 (screening) to grade 3 (days 42 and 98). The dog's overall weight improved significantly during the treatment period (40.5 kg at screening, 44.2 kg on day 42, and 43.8 kg on day 98). The owner confirmed that the dog's overall condition had improved and that its exercise tolerance over the past 7 days had been normal and good. The second dog included has been diagnosed with DCM stage B2. The dog has only recently joined the ongoing experiment, and data from follow-up visits are not yet available.

[0182] This field study evaluates the combination therapy of veragliflozin administered orally once daily and pimobendan administered orally twice daily in dogs with mitral valve disease (MVD). The described experiment is a prospective, baseline-controlled, open-label, multicenter exploratory clinical field trial. Owner-owned dogs diagnosed with MVD were randomly selected at different locations to receive either pimobendan or veragliflozin and pimobendan. Eight dogs were successfully enrolled. One dog was excluded from further study participation because it did not attend any follow-up visits. Therefore, data from seven dogs are presented below. The clinical field trial is still ongoing. The dogs participating in the experiment will be regularly evaluated, including a comprehensive health check including weight, blood pressure, and auscultation of the cardiovascular system, chest X-rays to assess heart size, pulmonary edema and congestion, standard echocardiography, ECG, blood tests and urinalysis. Cardiovascular history is assessed by reviewing the date of diagnosis of MVD and whether or not there is a history of heart failure. During the experiment, owner questionnaires are regularly collected to provide an overview of the dog's overall condition, resting respiratory rate, and exercise tolerance over the past 7 days of treatment.

[0183] The dogs included must have been diagnosed with MVD stage B2 or stage C via health examination and echocardiography. The variables to be considered are all clinical parameters evaluated in addition to laboratory values, blood pressure, number of events (death, hospitalization due to heart failure, or euthanasia), time to event, adjustment of diuretic treatment, owner questionnaire data, X-ray results, and overall disease progression (need for additional, prohibited cardiac treatment). During the ongoing field trial, three dogs are receiving a combination therapy of veragliflozin (0.5 mg / kg body weight orally once daily) and pimobendan (0.5 mg / kg body weight orally in two divided doses, which may not necessarily be equal).

[0184] The results for the first dog, which was classified and included in ACVIM Stage B2, confirmed improvement in echocardiographic parameters (at days 43 and 96) as assessed via the MINE scoring system. The score improved by 1 point from 7 to 6 points at day 43 (still moderately affected) and by 6 to 5 points at day 96. Based on the score at day 96, this dog's classification improved to mild disease. The dog showed a positive decrease in the LA / Ao ratio from 1.77 (screening) to 1.70 (day 96). The overall condition and other key parameters (i.e., owner score, blood pressure, and blood parameters) remained stable. The second dog is also classified as ACVIM stage B2. The dog is showing disease progression as expected for a dog considered severely affected, considering the pathology of the disease, and the MINE score for echocardiographic parameters worsened on day 49 (an increase of 2 score points from 7 to 9, indicating a transition from moderate to severe disease). The heart murmur diagnosed by the veterinarian on cardiac auscultation improved from a very loud murmur (screening) to a loud murmur (day 49). This is considered a positive therapeutic effect. The owner questionnaire consistently confirmed a good overall condition and good exercise tolerance.

[0185] The third dog, classified as ACVIM stage B2, showed a positive response at day 55, with its MINE score remaining stable relative to measured echocardiographic parameters. The dog has a MINE score of 10 points, classifying it as a severely affected dog. The LA / Ao ratio has prospectively decreased from 2.49 (screening) to 2.35 (day 55). Overall, the dog shows a positive therapeutic response, assuming standard disease progression at a particular severity level. During the ongoing field trial, four dogs are receiving treatment with pimobendan alone (0.5 mg / kg body weight per day, administered orally in two unequal doses). In the first dog, a deterioration in the MINE score was observed on day 88 (a decline from 7 to 8). This indicates that the dog is progressing from a moderate to severe condition. Other parameters measured (i.e., heart murmurs) remained largely unchanged.

[0186] The second dog shows a stable MINE score for the measured echocardiographic parameters. The score remains at 8 points (day 55), but the dog is classified as severely ill. The dog's Echo-Parameter LA / Ao improved from 2.14 (screening) to 1.96 (day 55), and the dog's owner also reported an improvement in the dog's overall condition and exercise tolerance over the past 7 days. The third dog also showed an improvement in its overall owner score [change from normal (screening) to good (day 48)]. The Echo-Parameter LA / Ao was measured on day 48 and improved from 1.60 at screening to 1.53. The fourth dog showed improvement in its owner score on day 42. In the seven days prior to screening, its overall condition was normal and its exercise tolerance was very poor, but this has improved, and the owner now reports that the dog's overall condition is good and its exercise tolerance is good. The Echo Parameter LA / Ao also decreased positively from 1.88 (screening) to 1.61 (day 42). The MINE score also reflects this improvement [8 score points (screening), 6 score points (day 42)].

[0187] Overall summary While it is known that pimobendan has beneficial effects in dogs with cardiac disease, such as DCM and MVD, the data described in the above clinical trial show that dogs treated with the combination of pimobendan and veragliflozin exhibited additional improvements in cardiovascular parameters that would not be expected with pimobendan monotherapy (e.g., reduced systolic blood pressure, reduced heart murmur intensity) or veragliflozin monotherapy. Body weight remained stable in all treatment groups, but DCM dogs treated with pimobendan and veragliflozin showed a noticeable increase. Therefore, it can be concluded that the combination of treatment with a positive inotropic agent such as pimobendan and an SGLT2 inhibitor such as veragliflozin provides synergistic and beneficial effects in dogs with cardiac disease such as DCM or MVD that exceed the benefits of monotherapy.

[0188] (Example 17) Laboratory testing (DCM model) The laboratory trial will evaluate the efficacy of the SGLT2 inhibitors veragliflozin and pimobendan compared to pimobendan alone and veragliflozin alone in dogs with moderate, frequent pacing-induced heart failure [dilated cardiomyopathy (DCM) model]. The trial will involve 12 beagle dogs, divided into three treatment groups, each containing 4 dogs for two treatment phases (a total of 8 dogs per group). The treatment groups will be pimobendan, veragliflozin, and a combination of both (pimobendan + veragliflozin).

[0189] Dogs are implanted with a pacing generator in the right ventricle (Abbott-Johnson K et al., 2021) and administered two doses over a three-month period. Before the start of each dose round, moderate heart failure (EF = approximately 40-45%) is induced to maintain the pacing rate throughout the three-month treatment period. After each round, a washout period of approximately 21-28 days is provided before the start of the next dose round. Various data will be collected throughout the trial, including a 6-minute walk test, blood and urine analysis, and echocardiogram data. At the end of each 3-month medication round, the dogs will undergo recovery under anesthesia, during which their systemic hemodynamics will be recorded. At the end of each 3-month period, a single dose of dobutamine will also be administered to measure functional reserve. The results show that both dogs treated with veragliflozin and dogs treated with combination therapy exhibit elevated urinary glucose and decreased creatinine levels, based on the mechanism of action of SGLT2 inhibitors. Pimobendan did not affect either urinary glucose or creatinine levels.

[0190] Comparing values ​​indicating cardiac systolic function and performance, approximately 30% enhancement was observed compared to pimobendan and approximately 50% enhancement compared to the combination group (i.e., EF, FAS, Simpson EF, s' wave, LVOT VTI, SV, CO, or SAX Strain). In terms of cardiac diastolic function and performance, approximately 20% enhancement was observed compared to pimobendan and approximately 35% enhancement compared to the combination group (i.e., IVRT, E, E' mean). Little to no assistance was obtained in helping to enhance contractility or improve relaxation as veragliflozin alone provided.

[0191] Overall, all treatments have proven beneficial, with all groups showing a 25-30% increase in these 6-minute walk tests from baseline. Treatment with pimobendan enhanced cardiac systolic and diastolic performance, leading to clear and strong functional support over a 3-month period. The combination therapy of veragliflozin and pimobendan clearly enhances cardiac function compared to veragliflozin or pimobendan monotherapy. The combination group measured the highest contractility, lowest cardiac filling pressure, lowest mean right atrial pressure, and used the least amount of mechanical energy per cardiac cycle. In summary, the combination therapy of veragliflozin and pimobendan shows a mutually beneficial effect in dogs with moderate, frequent pacing-induced heart failure mimicking diamniotic comorbidity (DCM).

[0192] List of abbreviations: [Table 1]

[0193] References JPEG2026517461000053.jpg192161 JPEG2026517461000054.jpg150156

[0194] The following provisions are also within the spirit of the invention and are therefore part of this disclosure. Further combination of the subject matter of the following provisions with any further aspects, embodiments and / or preferred embodiments disclosed herein is also within the spirit of the invention and this disclosure. 1. One or more SGLT-2 inhibitors, or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use as a pharmaceutical. 2. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for use as described in Clause 1, in methods for preventing and / or treating one or more cardiac diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / felines. 3. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for use as described in Clause 2, in a method for treating one or more cardiac diseases in non-human mammals / non-human mammalian animals, particularly canids / canine animals or felines / feline animals.

[0195] 4. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in Clause 2 or Clause 3, wherein one or more cardiac diseases are acquired heart disease; congenital heart disease; heart failure; congestive heart failure; asymptomatic / preclinical / occult heart failure; heart failure due to (primitive mesenchymal) mitral valve disease [(M)MVD]; (primitive mesenchymal) mitral valve disease Congestive heart failure due to mitral valve disease [(M)MVD]; Asymptomatic / preclinical / latent heart failure due to (primitive mesenchymal) mitral valve disease [(M)MVD]; (primitive mesenchymal) mitral valve disease [(M)MVD]; Clinically evident (primitive mesenchymal) mitral valve disease [(M)MVD]; Asymptomatic / preclinical / latent (primitive mesenchymal) mitral valve disease [(M)MVD]; Heart failure due to dilated cardiomyopathy (DCM); Congestive heart failure due to dilated cardiomyopathy (DCM); Dialysis Asymptomatic / preclinical / latent heart failure due to dilated cardiomyopathy (DCM); dilated cardiomyopathy (DCM); clinically evident dilated cardiomyopathy (DCM); asymptomatic / preclinical / latent dilated cardiomyopathy (DCM); aortic stenosis (valvular, supravalvular and / or subvalvular); heart failure due to one or more cardiomyopathy types; heart failure due to hypertrophic cardiomyopathy (HCM); heart failure due to hypertrophic obstructive cardiomyopathy (HOCM); heart failure due to restrictive cardiomyopathy (RCM); heart failure due to dilated cardiomyopathy (DCM); heart failure due to unclassifiable cardiomyopathy (UCM); heart failure due to arrhythmic right ventricular cardiomyopathy (ARVC); one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof selected from the group consisting of hypertrophic cardiomyopathy (HCM); hypertrophic obstructive cardiomyopathy (HOCM); restrictive cardiomyopathy (RCM); dilated cardiomyopathy (DCM); unclassifiable cardiomyopathy (UCM); and / or arrhythmic right ventricular cardiomyopathy (ARVC).

[0196] 5. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use as described in Clause 4, wherein one or more cardiac diseases are acquired; congenital cardiac diseases; heart failure; congestive heart failure; asymptomatic / preclinical / occult heart failure; (primitive mesenchymal) mitral valve disease [(M)MVD]; clinically apparent (primitive mesenchymal) mitral valve disease [(M)MVD]; asymptomatic / preclinical / occult (primitive mesenchymal) mitral valve disease [(M)MVD]; dilated cardiomyopathy (DCM); One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, selected from the group consisting of clinically evident dilated cardiomyopathy (DCM); asymptomatic / preclinical / latent dilated cardiomyopathy (DCM); and aortic stenosis (valvular, supravalvular and / or subvalvular), wherein the non-human mammal / non-human mammalian patient is a canid / canid patient, preferably a canid patient requiring such prophylaxis and / or treatment, more preferably a dog requiring such prophylaxis and / or treatment, and even more preferably a non-diabetic dog requiring such prophylaxis and / or treatment.

[0197] 6. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use as described in Clause 4, wherein one or more cardiac diseases are acquired; congenital cardiac diseases; heart failure; congestive heart failure; asymptomatic / preclinical / occult heart failure; heart failure due to one or more cardiomyopathy; heart failure due to hypertrophic cardiomyopathy (HCM); heart failure due to hypertrophic obstructive cardiomyopathy (HOCM); heart failure due to restrictive cardiomyopathy (RCM); heart failure due to dilated cardiomyopathy (DCM); heart failure due to unclassifiable cardiomyopathy (UCM); proarrhythmic right ventricle One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, selected from the group consisting of heart failure due to cardiomyopathy (ARVC); hypertrophic cardiomyopathy (HCM); hypertrophic obstructive cardiomyopathy (HOCM); restrictive cardiomyopathy (RCM); dilated cardiomyopathy (DCM); unclassifiable cardiomyopathy (UCM); and / or proarrhythmic right ventricular cardiomyopathy (ARVC), wherein the non-human mammal / non-human mammalian patient is a feline / feline patient, preferably a feline patient requiring such prophylaxis and / or treatment, more preferably a cat requiring such prophylaxis and / or treatment, and even more preferably a non-diabetic cat requiring such prophylaxis and / or treatment.

[0198] 7. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of paragraphs 1 to 6, wherein one or more SGLT-2 inhibitors are (1) Glucopyranosyl-substituted benzene derivative of formula (1) [ka] (In the formula, R 1 represents cyano, Cl, or methyl (most preferably cyano), R 2 represents H, methyl, methoxy, or hydroxy (most preferably H), R 3This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propane-1-yl, 3-hydroxy- Represents 3-methylbuta-1-yl, 1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethylethyl, 2-methoxyethyl, 2-ethoxyethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxyethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano, R 3 The compound is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy, most preferably R 3 (It is cyclopropyl), or a derivative thereof, wherein one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 Acylated with a group selected from -alkyl)-carbonyl groups;

[0199] (2) Veragliflozin represented by formula (2): [ka]

[0200] (3) Dapagliflozin represented by formula (3): [ka]

[0201] (4) Canagliflozin represented by formula (4): [ka]

[0202] (5) Empagliflozin represented by formula (5): [ka] (6) Luseogliflozin represented by formula (6): [ka]

[0203] (7) Tofogliflozin represented by formula (7): [ka]

[0204] (8) Ipragliflozin represented by formula (8): [ka] (9) Erzggliflozin represented by formula (9): [ka]

[0205] (10) Atigliflozin represented by formula (10): [ka]

[0206] (11) Remogliflozin represented by formula (11): [ka]

[0207] (11A) Remogliflozin etabonate represented by formula (11A): [ka]

[0208] (12) Thiofen derivatives of formula (12) [ka] (In the formula, R represents methoxy or trifluoromethoxy, (13) 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene represented by formula (13); [ka]

[0209] (14) Spirochetal derivatives of formula (14): [ka] (wherein R represents methoxy, trifluoromethoxy, ethoxy, ethyl, isopropyl, or tert.butyl);

[0210] (15) Pyrazole-O-glucoside derivatives of formula (15): [ka] (In the formula, R 1 is C 1-3 - Represents alkoxy, L 1 , L 2 These represent H or F independently of each other. R 6 H, (C1-3 -alkyl)carbonyl, (C 1-6 (Represents alkyl)oxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, or benzylcarbonyl)

[0211] (16) Sotagliflozin represented by formula (16): [ka] (17) Cergliflozin represented by formula (17): [ka]

[0212] (18) Compounds represented by formula (18): [ka] (In the formula, R 3This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-propane-1-yl, 3-hydroxy- 3-methylbuta-1-yl, 1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-methylethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethylethyl, 2-methoxyethyl, 2-ethoxyethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxyethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano, R 3 The compound is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy, most preferably R 3 (It is cyclopropyl), or a derivative thereof, wherein one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 Acylated with a group selected from -alkyl)-carbonyl groups;

[0213] (19) Bexagliflozin represented by formula (19): [ka]

[0214] (20) Janagliflozin represented by formula (20): [ka]

[0215] (21) Long liflozin represented by formula (21): [ka] (22) Wampagliflozin;

[0216] (23) Enabogliflozin represented by formula (23): [ka]

[0217] (24) TFC-039 represented by formula (24) [ka] One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, selected from the group consisting of the following.

[0218] 8. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of Clauses 1 to 7, wherein the pharmaceutically acceptable form is a crystalline complex of one or more SGLT-2 inhibitors and one or more amino acids, preferably proline, more preferably L-proline, most preferably a cocrystal of one or more SGLT2 inhibitors, L-proline, and water of crystallization. 9. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of paragraphs 1 to 8, wherein veragliflozin or a pharmaceutically acceptable form thereof is administered as a single SGLT-2 inhibitor in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, preferably veragliflozin or a pharmaceutically acceptable form thereof is administered in combination with pimobendan as a single SGLT-2 inhibitor.

[0219] 10. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of paragraphs 1 to 9, wherein veragliflozin or a pharmaceutically acceptable form thereof is used as a single SGLT-2 inhibitor, and the use is in a method of preventing and / or treating DCM or MVD in canids / canine animals. 11. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of paragraphs 1 to 9, wherein veragliflozin or a pharmaceutically acceptable form thereof is used as a single SGLT-2 inhibitor, and the use is in a manner for the prevention and / or treatment of HCM in felines / feline animals.

[0220] 12. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of paragraphs 1 to 9, wherein veragliflozin or a pharmaceutically acceptable form thereof is used as a single SGLT-2 inhibitor, and the use is in a manner for treating DCM or MVD in canids / canine animals. 13. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of paragraphs 1 to 9, wherein veragliflozin or a pharmaceutically acceptable form thereof is used as a single SGLT-2 inhibitor, and the use is in a manner for treating HCM in felines / feline animals.

[0221] 14. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of paragraphs 1 to 9, wherein veragliflozin or a pharmaceutically acceptable form thereof is used as a single SGLT-2 inhibitor, and the use is in combination with pimobendan in a method of treating DCM or MVD in canids / canine animals.

[0222] 15. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of paragraphs 1 to 9, wherein veragliflozin or a pharmaceutically acceptable form thereof is used as a single SGLT-2 inhibitor. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof for use in combination with pimobendan in methods of treating HCM in felines / feline animals. 16. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use as described in any one of Clauses 1 to 15, wherein one or more SGLT-2 inhibitors or a pharmaceutically acceptable form thereof is administered orally, parenterally, intravenously, subcutaneously, or intramuscularly, preferably orally.

[0223] 17. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of paragraphs 1 to 16, wherein one or more SGLT-2 inhibitors or a pharmaceutically acceptable form thereof is administered in a dose of 0.01 mg / kg body weight to 10 mg / kg body weight per day, preferably 0.01 mg / kg body weight to 5 mg / kg body weight per day, and more preferably 0.01 mg / kg body weight to 4 mg / kg body weight per day. More preferably, one or more SGLT-2 inhibitors or a pharmaceutically acceptable form thereof, administered at a dose of 0.01 mg / kg body weight to 3 mg / kg body weight per day, even more preferably at a dose of 0.01 mg / kg body weight to 2 mg / kg body weight per day, even more preferably at a dose of 0.01 mg / kg body weight to 1 mg / kg body weight per day, even more preferably at a dose of 0.01 mg / kg body weight to 0.5 mg / kg body weight per day, and most preferably at a dose of 0.01 mg / kg body weight to 0.3 mg / kg body weight per day. 18. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of Clauses 1 to 17, wherein such one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof are administered once or twice daily, preferably once daily.

[0224] 19. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of paragraphs 1 to 18, wherein pimobendan is administered at a dose of 0.1 mg / kg body weight to 1 mg / kg body weight per day, preferably 0.2 mg / kg body weight to 0.6 mg / kg body weight per day, more preferably 0.5 mg / kg body weight per day.

[0225] 20. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of Clauses 1 to 19, wherein pimobendan is administered once or twice daily, preferably twice daily, more preferably every 12 hours. 21. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof for use as described in any one of Clauses 1 to 20, wherein one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof are administered in combination with pimobendan and telmisartan or pharmaceutically acceptable forms thereof, preferably one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof are administered before, after, or concurrently with the administration of pimobendan and telmisartan or pharmaceutically acceptable forms thereof.

[0226] 22. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of Clauses 1 to 21, wherein telmisartan or a pharmaceutically acceptable form thereof is administered in a dose of 0.01 to 10 mg / kg body weight per day, preferably 0.05 to 8 mg / kg body weight per day, more preferably 0.1 to 5 mg / kg body weight per day, more preferably 0.2 to 4 mg / kg body weight per day, more preferably 0.3 to 3 mg / kg body weight per day, more preferably 0.4 to 2.5 mg / kg body weight per day, more preferably 0.5 to 2 mg / kg body weight per day, and most preferably 0.75 to 1.5 mg / kg body weight per day. 23. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in any one of Clauses 1 to 22, wherein telmisartan or a pharmaceutically acceptable form thereof is administered once or twice daily, preferably twice daily, more preferably every 12 hours.

[0227] 24. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use as described in any one of paragraphs 1 to 23, wherein the prophylactic and / or therapeutic effect is one or more of the following clinical and / or biochemical parameters: - Improved cardiovascular metabolic efficiency characterized by an increased ratio of [cardiac output / metabolic substrates consumed] and / or an increased ratio of [cardiac output / oxygen consumed]; - Increased ketone body production in the liver, characterized by increased plasma levels of 3-hydroxybutyrate and / or the corresponding acylcarnitine, i.e., hydroxybutyrylcarnitine, and increased plasma levels of one or more branched-chain amino acids (valine, leucine, and isoleucine); - Improved cardiac function and improved arterial wall structural function achieved by reducing preload and / or afterload; - Improved cardiac ultrasound parameters, e.g., reduced LA (left atrial dimension measured as the right parasternal short axis), LA / Ao (left atrial to aortic ratio; Ao = diameter of the aortic root), IVSd (cardiac diastolic dimension of the terminal ventricular septum, i.e., thickness of the ventricular septum), and / or LAD (left atrial dimension measured as the right parasternal long axis), as well as improved cardiac biomarkers, e.g., reduced NT-proBNP (N-terminal pro-brain natriuretic peptide) and / or reduced cTnI (cardiac troponin I) and / or increased erythropoietin concentration, and / or changes in metabolites indicating changes in the cardiac energy source; and improved heart murmurs; - Delay in the onset of different phenotypic cardiac diseases, e.g., (M)MVD and / or DCM and / or cardiomyopathy, preferably a delay of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 months or longer, or furthermore, cessation of the progression of different phenotypic cardiac diseases, e.g., (M)MVD and / or DCM, and / or cardiomyopathy; - An extension of survival time, preferably at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 months or longer, and / or a delay in the onset of the following symptoms of heart failure, preferably at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 months or longer, and / or a lower level of cardiac mortality and / or morbidity; - Improved clinical signs, such as shortness of breath or difficulty breathing, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension and / or decreased polydipsia; - Prolonged time to an event (e.g., heart failure, cardiac death, onset of clinical signs, need for additional concomitant medications, increased dose of concomitant therapy-diuretics); - Prevention of fibrosis; - Prevention of cardiomyocyte death / protection of cardiomyocytes (reduction of oxidative stress); - Increased flexibility of blood vessel walls; - Prevention of high blood pressure; - A higher quality of life One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, characterized by the above.

[0228] 25. A pharmaceutical composition comprising one or more SGLT2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as defined in any one of Clauses 1 to 24, wherein the pharmaceutical composition is preferably a fixed-dose combination (FDC) of one or more SGLT-2 inhibitors or a pharmaceutically acceptable form thereof and pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, and more preferably the FDC is a solid or liquid formulation.

Claims

1. One or more SGLT-2 inhibitors, or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use as a pharmaceutical.

2. A method for preventing and / or treating one or more heart diseases in non-human mammals / non-human mammalian animals, particularly canids / canid animals or felines / feline animals, comprising one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as described in claim 1.

3. A method for treating one or more cardiac diseases in non-human mammals / non-human mammalian animals, particularly canids / canine animals or felines / feline animals, comprising one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use according to claim 2.

4. One or more types of heart disease are classified as: acquired heart disease; congenital heart disease; heart failure; congestive heart failure; asymptomatic / preclinical / latent heart failure; heart failure due to (primitive mesenchymal) mitral valve disease [(M)MVD]; congestive heart failure due to (primitive mesenchymal) mitral valve disease [(M)MVD]; asymptomatic / preclinical / latent heart failure due to (primitive mesenchymal) mitral valve disease [(M)MVD]; clinical Obvious (primitive mesenchymal) mitral valve disease [(M)MVD]; asymptomatic / preclinical / latent (primitive mesenchymal) mitral valve disease [(M)MVD]; heart failure due to dilated cardiomyopathy (DCM); congestive heart failure due to dilated cardiomyopathy (DCM); asymptomatic / preclinical / latent heart failure due to dilated cardiomyopathy (DCM); dilated cardiomyopathy (DCM); clinically evident dilated cardiomyopathy (DCM); asymptomatic / preclinical / latent dilated cardiomyopathy (D CM); aortic stenosis (valvular, supravalvular and / or subvalvular); heart failure due to one or more cardiomyopathy; heart failure due to hypertrophic cardiomyopathy (HCM); heart failure due to hypertrophic obstructive cardiomyopathy (HOCM); heart failure due to restrictive cardiomyopathy (RCM); heart failure due to dilated cardiomyopathy (DCM); heart failure due to unclassifiable cardiomyopathy (UCM); heart failure due to arrhythmic right ventricular cardiomyopathy (ARVC); one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use according to claim 2 or 3, selected from the group consisting of hypertrophic cardiomyopathy (HCM); hypertrophic obstructive cardiomyopathy (HOCM); restrictive cardiomyopathy (RCM); dilated cardiomyopathy (DCM); unclassifiable cardiomyopathy (UCM); and / or arrhythmic right ventricular cardiomyopathy (ARVC).

5. One or more types of heart disease are selected from the group consisting of acquired heart disease; congenital heart disease; heart failure; congestive heart failure; asymptomatic / preclinical / occult heart failure; (primitive mesenchymal) mitral valve disease [(M)MVD]; clinically evident (primitive mesenchymal) mitral valve disease [(M)MVD]; asymptomatic / preclinical / occult (primitive mesenchymal) mitral valve disease [(M)MVD]; dilated cardiomyopathy (DCM); clinically evident dilated cardiomyopathy (DCM); asymptomatic / preclinical / occult dilated cardiomyopathy (DCM); and aortic stenosis (valvular, supravalvular and / or subvalvular). , nonhuman mammal / nonhuman mammal affected animal is canid / canid affected animal, preferably canid affected animal requiring such prevention and / or treatment, more preferably dog ​​requiring such prevention and / or treatment, even more preferably non-diabetic dog requiring such prevention and / or treatment, one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use according to claim 4.

6. One or more types of heart disease: acquired heart disease; congenital heart disease; heart failure; congestive heart failure; asymptomatic / preclinical / occult heart failure; heart failure due to one or more types of cardiomyopathy; heart failure due to hypertrophic cardiomyopathy (HCM); heart failure due to hypertrophic obstructive cardiomyopathy (HOCM); heart failure due to restrictive cardiomyopathy (RCM); heart failure due to dilated cardiomyopathy (DCM); heart failure due to unclassified cardiomyopathy (UCM); heart failure due to arrhythmic right ventricular cardiomyopathy (ARVC); hypertrophic cardiomyopathy (HCM); hypertrophic obstructive cardiomyopathy (HOCM); restrictive cardiomyopathy (RCM); dilated cardiomyopathy (DCM); unclassified cardiomyopathy One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use according to claim 4, selected from the group consisting of disease (UCM); and / or proarrhythmic right ventricular cardiomyopathy (ARVC), wherein the non-human mammal / non-human mammalian patient is a feline / feline patient, preferably a feline patient requiring such prophylaxis and / or treatment, more preferably a cat requiring such prophylaxis and / or treatment, and even more preferably a non-diabetic cat requiring such prophylaxis and / or treatment.

7. One or more SGLT-2 inhibitors, (1) Glucopyranosyl-substituted benzene derivative of formula (1) 【Chemistry 1】 (In the formula, R 1 represents cyano, Cl, or methyl (most preferably cyano), R 2 represents H, methyl, methoxy, or hydroxy (most preferably H), R 3 This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxycyclopropyl, 1-hydroxycyclobutyl, 1-hydroxycyclopentyl, 1-hydroxycyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxypropyl, 2-hydroxy-2-methylpropane-1-yl, 3-hydroxy Represents 3-methylbuta-1-yl, 1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl, 2-methoxy-ethyl, 2-ethoxy-ethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxy-ethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano, R 3 The is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy, most preferably R 3 (It is cyclopropyl.) or a derivative thereof, wherein one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -Alkyl)carbonyl, (C 1-18 -Alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 Acylated with a group selected from -alkyl-carbonyl groups; (2) Veragliflozin represented by formula (2): 【Chemistry 2】 (3) Dapagliflozin represented by formula (3): 【Transformation 3】 (4) Canagliflozin represented by formula (4): 【Chemistry 4】 (5) Empagliflozin represented by formula (5): 【Transformation 5】 (6) Luseogliflozin represented by formula (6): 【Transformation 6】 (7) Tofogliflozin represented by formula (7): 【Transformation 7】 (8) Ipragliflozin represented by formula (8): 【Transformation 8】 (9) Erzggliflozin represented by formula (9): 【Chemistry 9】 (10) Atigliflozin represented by formula (10): 【Chemistry 10】 (11) Remogliflozin represented by formula (11): 【Chemistry 11】 (11A) Lemogliflozin etabonate represented by formula (11A): 【Chemistry 12】 (12) Thiophene derivatives of formula (12) 【Chemistry 13】 (In the formula, R represents methoxy or trifluoromethoxy); (13) 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene represented by formula (13); 【Chemistry 14】 (14) Spirochetal derivative of formula (14): 【Chemistry 15】 (wherein R represents methoxy, trifluoromethoxy, ethoxy, ethyl, isopropyl, or tert.butyl); (15) Pyrazole-O-glucoside derivatives of formula (15): 【Chemistry 16】 (In the formula, R 1 represents C 1-3 -alkoxy, and L 1 , L 2 These represent H or F independently of each other. R 6 H, (C 1-3 -Alkyl)carbonyl, (C 1-6 (- Represents alkyl)oxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, or benzylcarbonyl); (16) Sotagliflozin represented by formula (16): 【Chemistry 17】 (17) Cergliflozin represented by formula (17): [Chemistry 18] (18) Compounds represented by formula (18): 【Chemistry 19】 (In the formula, R 3 This includes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methylbuta-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxycyclopropyl, 1-hydroxycyclobutyl, 1-hydroxycyclopentyl, 1-hydroxycyclohexyl, ethynyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxypropyl, 2-hydroxy-2-methylpropane-1-yl, 3-hydroxy 3-methylbuta-1-yl, 1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl, 2-methoxy-ethyl, 2-ethoxy-ethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxy-ethyloxy, methylsulfanyl, methylsulfinyl, methylsulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano, R 3 The is preferably selected from cyclopropyl, ethyl, ethynyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy, most preferably R 3 (It is cyclopropyl.) or a derivative thereof, wherein one or more hydroxyl groups of the β-D-glucopyranosyl group are (C 1-18 -Alkyl)carbonyl, (C 1-18 -Alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 Acylated with a group selected from -alkyl-carbonyl groups; (19) Bexagliflozin represented by formula (19): 【Chemistry 20】 (20) Janagliflozin represented by formula (20): 【Chemistry 21】 (21) Long liflozin represented by formula (21): 【Chemistry 22】 (22) Wampagliflozin; (23) Enabogliflozin represented by formula (23): 【Chemistry 23】 (24) TFC-039 represented by formula (24) 【Chemistry 24】 One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, selected from the group consisting of the following, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use according to any one of claims 1 to 6.

8. The pharmaceutically acceptable form is a crystalline complex of one or more SGLT-2 inhibitors and one or more amino acids, preferably proline, more preferably L-proline, most preferably a cocrystal of one or more SGLT-2 inhibitors, L-proline, and water of crystallization, as described in any one of claims 1 to 7, wherein the pharmaceutically acceptable form is one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof.

9. Veragliflozin or a pharmaceutically acceptable form thereof is administered in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof as a single SGLT-2 inhibitor, preferably veragliflozin or a pharmaceutically acceptable form thereof is administered in combination with pimobendan as a single SGLT-2 inhibitor, one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use according to any one of claims 1 to 8.

10. Veragliflozin or a pharmaceutically acceptable form thereof is used as a single SGLT-2 inhibitor, and the use is in a method of preventing and / or treating DCM or MVD in canids / canid animals, one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use according to any one of claims 1 to 9.

11. Veragliflozin or a pharmaceutically acceptable form thereof is used as a single SGLT-2 inhibitor, and the use is in a method of preventing and / or treating HCM in felines / feline animals, one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use according to any one of claims 1 to 9.

12. Veragliflozin or a pharmaceutically acceptable form thereof is used as a single SGLT-2 inhibitor, and the use is in a method of treating DCM or MVD in canids / canid animals, one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use according to any one of claims 1 to 9.

13. Veragliflozin or a pharmaceutically acceptable form thereof is used as a single SGLT-2 inhibitor, and the use is in a method of treating HCM in felines / feline animals, one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use according to any one of claims 1 to 9.

14. Veragliflozin or a pharmaceutically acceptable form thereof is used as a single SGLT-2 inhibitor, and the use is in combination with pimobendan in a method of treating DCM or MVD in canids / canid animals, one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use according to any one of claims 1 to 9.

15. Veragliflozin or a pharmaceutically acceptable form thereof is used as a single SGLT-2 inhibitor, and the use is in combination with pimobendan in a method for treating HCM in felines / feline animals, one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use according to any one of claims 1 to 9.

16. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof, for use according to any one of claims 1 to 15, wherein one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof are administered orally, parenterally, intravenously, subcutaneously, or intramuscularly, preferably orally.

17. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof are administered in a dose of 0.01 mg / kg body weight to 10 mg / kg body weight per day, preferably 0.01 mg / kg body weight to 5 mg / kg body weight per day, more preferably 0.01 mg / kg body weight to 4 mg / kg body weight per day, even more preferably 0.01 mg / kg body weight to 3 mg / kg body weight per day, even more preferably 0.01 mg / kg body weight to 2 mg / kg body weight per day, and furthermore One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use according to any one of claims 1 to 16, preferably administered at a dose of 0.01 mg / kg body weight to 1 mg / kg body weight per day, more preferably at a dose of 0.01 mg / kg body weight to 0.5 mg / kg body weight per day, and most preferably at a dose of 0.01 mg / kg body weight to 0.3 mg / kg body weight per day.

18. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or pharmaceutically acceptable forms thereof, for use according to any one of claims 1 to 17, wherein one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof are administered once or twice daily, preferably once daily.

19. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use according to any one of claims 1 to 18, wherein pimobendan is administered at a dose of 0.1 mg / kg body weight to 1 mg / kg body weight per day, preferably 0.2 mg / kg body weight to 0.6 mg / kg body weight per day, more preferably 0.5 mg / kg body weight per day.

20. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use according to any one of claims 1 to 19, wherein pimobendan is administered once or twice daily, preferably twice daily, more preferably every 12 hours.

21. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof are administered in combination with pimobendan and telmisartan or pharmaceutically acceptable forms thereof, preferably before, after, or concurrently with the administration of pimobendan and telmisartan or pharmaceutically acceptable forms thereof, according to any one of claims 1 to 20.

22. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, for use according to any one of claims 1 to 21, wherein telmisartan or a pharmaceutically acceptable form thereof is administered in a dose of 0.01 to 10 mg / kg body weight per day, preferably 0.05 to 8 mg / kg body weight per day, more preferably 0.1 to 5 mg / kg body weight per day, more preferably 0.2 to 4 mg / kg body weight per day, more preferably 0.3 to 3 mg / kg body weight per day, more preferably 0.4 to 2.5 mg / kg body weight per day, more preferably 0.5 to 2 mg / kg body weight per day, most preferably 0.75 to 1.5 mg / kg body weight per day.

23. One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, used according to any one of claims 1 to 22, wherein telmisartan or a pharmaceutically acceptable form thereof is administered once or twice daily, preferably twice daily, more preferably every 12 hours.

24. The prophylactic and / or therapeutic effect is due to one or more of the following clinical and / or biochemical parameters: - Improved cardiovascular metabolic efficiency characterized by an increased ratio of [cardiac output / metabolic substrates consumed] and / or an increased ratio of [cardiac output / oxygen consumed]; - Increased ketone body production in the liver, characterized by increased plasma levels of 3-hydroxybutyrate and / or the corresponding acylcarnitine, i.e., hydroxybutyrylcarnitine, and increased plasma levels of one or more branched amino acids (valine, leucine, and isoleucine); - Improved cardiac function and improved arterial wall structural function achieved by reducing preload and / or afterload; - Improved cardiac ultrasound parameters, e.g., reduced LA (left atrial dimension measured as the right parasternal short axis), LA / Ao (left atrial to aortic ratio; Ao = diameter of the aortic root), IVSd (cardiac diastolic dimension of the terminal ventricular septum, i.e., thickness of the ventricular septum), and / or LAD (left atrial dimension measured as the right parasternal long axis), as well as improved cardiac biomarkers, e.g., reduced NT-proBNP (N-terminal pro-brain natriuretic peptide) and / or reduced cTnI (cardiac troponin I) and / or increased erythropoietin concentration, and / or changes in metabolites indicating changes in the cardiac energy source; and improved heart murmurs; - Delay in the onset of different phenotypic cardiac diseases, e.g., (M)MVD and / or DCM and / or cardiomyopathy, preferably a delay of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 months or longer, or furthermore, cessation of the progression of different phenotypic cardiac diseases, e.g., (M)MVD and / or DCM, and / or cardiomyopathy; - An extension of survival time, preferably at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 months or longer, and / or a delay in the onset of the following symptoms of heart failure, preferably at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 months or longer, and / or a lower level of cardiac mortality and / or morbidity; - Improved clinical signs, such as shortness of breath or dyspnea, cough, depression, decreased exercise tolerance, loss of appetite, syncope, abdominal distension and / or decreased polydipsia; - Prolongation of time to an event (e.g., heart failure, cardiac death, onset of clinical signs, need for additional concomitant medication, combination therapy - increase in diuretic dosage); - Prevention of fibrosis; - Prevention of cardiomyocyte death / Protection of cardiomyocytes (reduction of oxidative stress); - Increased flexibility of blood vessel walls; - Prevention of high blood pressure; - A higher quality of life One or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof, characterized by the use of pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, as described in any one of claims 1 to 23.

25. A pharmaceutical composition comprising one or more SGLT2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof for use as defined in any one of claims 1 to 24, wherein the pharmaceutical composition is preferably a fixed-dose combination (FDC) of one or more SGLT-2 inhibitors or a pharmaceutically acceptable form thereof and pimobendan and / or telmisartan or a pharmaceutically acceptable form thereof, and more preferably the FDC is a solid formulation or a liquid formulation.

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