Co-therapy comprising canagliflozin and phentermine for the treatment of obesity and obesity related disorders

Abstract

The present invention is directed to the use of co-therapy comprising administration of canagliflozin and phentermine for the treatment of obesity and obesity related disorders. More particularly, the present invention is directed to co-therapy for treating obesity, for promoting weight loss and/or for suppressing appetite; for treating, delaying, slowing the progression of and/or preventing metabolic disorders (including for example Type 2 diabetes mellitus); for treating, delaying, slowing the progression of and/or preventing renal or fatty liver disorders (including for example NASH, NAFLD, etc.); for treating, delaying, slowing the progression of and/or preventing sleep disorders (including for example sleep apnea); for providing cardiovascular protection; for treating, delaying, slowing the progression of and/or preventing cardiovascular events (including major adverse cardiac events (MACE) such as myocardial infarction, unstable angina, cardiovascular death, revascularization, fatal or non-fatal cerebrovascular accident, peripheral arteriopathy, aortic events, hospitalization due to congestive heart failure, etc.); and/or for extending or prolonging life span.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Patent Application No. 62 / 218,842, filed Sep. 15, 2015, and U.S. Provisional Patent Application No. 62 / 306,110, filed Mar. 10, 2016, the disclosures of which are hereby incorporated by reference in their entireties.FIELD OF THE INVENTION[0002]The present invention is directed to the use of co-therapy comprising administration of canagliflozin and phentermine for the treatment of obesity and obesity related disorders. More particularly, the present invention is directed to co-therapy for treating obesity, for promoting weight loss and / or for suppressing appetite; for treating, delaying, slowing the progression of and / or preventing metabolic disorders (including for example Type 2 diabetes mellitus); for treating, delaying, slowing the progression of and / or preventing renal or fatty liver disorders (including for example NASH, NAFLD, etc.); for treating, delaying, slowing the progression ...

AI Technical Summary

Benefits of technology

[0046]Recently published data indicates that BOHB is not simply an alternative metabolic fuel, but unexpectedly also has specific cell signaling and regulatory actions; actions that may mediate certain of the longevity-promoting effects associated with caloric restriction. In particular, BOHB has been shown to directly inhibit certain histone deacetylase enzymes (HDACs), and BOHB treatment of cultured cells increases histone acetylation, similar that observed with fasting in animals (SHIMAZU, T. et al. Suppression of Oxidative Stress by Beta-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor, Science, 2013, pp 211 Vol. 339). BOHB treatment of mice increases histone acetylation and thereby alters expression of certain genes associated with resistance to oxidative stress, notably the FOXO3 gene, a mammalian version of the transcription factor DAF16 that is a key regulator of lifespan in worms. HDAC inhibition by BOHB may also regulate the acetylation state and activity of non-histone proteins that also have cell protective effects.

[0047]Recently, BOHB was reported to inhibit the NLRP3 inflammasome, a sensor of the innate immune system which normally triggers inflammatory responses to a variety of injurious agents, such as excess glucose, urate, and amyloids that are associated with some chronic diseases. The known anti-inflammatory effects of fasting or ketogenic diets have been attributed to this effect of BOHB (YOUM, Y. H., et al., The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory...

Problems solved by technology

Obesity is more common among women and in the poor; the prevalence in children is also rising at a worrisome rate.

Obesity has major adverse effects on health.

There is also a higher probability of high blood pressure, sexual dysfunction, headaches, depression and sleep apnea.

People with diabetes either don't produce insulin, produce too little insulin or do not respond to insulin, resulting in the build up of glucose in the blood.

Damage to the nephrons represents an important form of kidney disease.

This damage may leave kidneys unable to remove wastes.

When the kidneys do not properly filter large molecules (such as albumin) from the urine, albumin is excreted in urine and is typically a sign of kidney damage or excessive salt intake.

Symptoms of sleep apnea include excessive daytime sleepiness (EDS) and impaired alertness.

In other words, common effects of sl...

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