Methods of using homotaurine and analogs thereof for the treatment of glucagon-like peptide 1 receptor agonist induced gastrointestinal side effects

Abstract

Disclosed are methods for reducing one or more gastrointestinal side effects in a subject receiving glucagon-like peptide-1 (GLP-1) receptor agonist (RA) therapy. The methods include administering to

Description

The disclosed invention is generally in the field of glucagon-like peptide 1 (GLP-1) receptor agonist therapy and specifically in the area of methods for treating GLP-1 receptor agonist induced gastrointestinal side effects. BACKGROUND OF THE INVENTION Diabetes mellitus (DM) and obesity are two of the most significant public health disorders (World Health Organization, Diabetes (2022), World Health Organization, Obesity and overweight (2022)). Diabetes mellitus is an endocrine disorder characterized by elevated blood glucose levels and classic symptoms such as thirst, polyuria, blurred vision, and weight loss (Gardner DG SD eds. Greenspan’s Basic &Clinical Endocrinology, 9e. 2011). The predominant forms of DM are type 1 and type 2, with type 2 accounting for an estimated 95% of Diabetes mellitus cases (World Health Organization, Diabetes (2022)). Currently, approximately 422 million people worldwide are diagnosed with diabetes, representing about 10.5% of the adult population (World Health Organization, Diabetes (2022), International Diabetes Federation, Diabetes facts and figures). Projections indicate that by 2045, about 783 million adults, or 1 in 8, will have diabetes, marking a 46% increase from current figures (International Diabetes Federation, Diabetes facts and figures). The annual global expenditure on diabetes-related healthcare is estimated at US$760 billion. Untreated DM can impact various organ systems, including the cardiovascular and nervous systems, potentially leading to severe health complications and approximately 1.5 million deaths annually (Gardner DG SD eds. Greenspan’s Basic &Clinical Endocrinology, 9e. 2011, International Diabetes Federation, Diabetes facts and figures; Bommer C, etal. Diabetes Care 41(5):963-70 (2018); BrutsaertEF. Diabetes Mellitus (DM) 2023; International Diabetes Federation). Obesity is recognized as a medical condition where excessive body fat accumulation may adversely affect health or quality of life and is considered a disease (Powell-Wiley TM, et al. Circulation 2021 May 25; 143(21): E984-1010; Bickel M, Schbning A. N Engl J Med 2017 Jul 6;377(1): 13-27 10). Factors contributing to obesity include diet, physical activity, genetics, lifestyle, medications, mental health, and endocrine disorders (Bouchard C. Am J Clin Nutr 2010 Jan;91(l):5-6; ChoquetH, Meyre D, Curr Genomics. 2011; 12(3): 169—79; Strohacker K, Carpenter KC, McFarlin BK. Int J Exerc Sci 2009;2(3): 191-201). Obesity can lead to serious health conditions and reduced life expectancy (Bickel M, Schoning A. N Engl J Med 2017 Jul 6;377(1): 13-27 10). In 2015, there were around 700 million people worldwide who were obese or overweight (Bickel M, Schoning A. N Engl J Med 2017 Jul 6;377(1): 13-27). One common treatment for type 2 DM involves glucagon-like peptide 1 receptor agonists (GLP-1 RAs). These drugs, including liraglutide, albiglutide, semaglutide, dulaglutide, exenatide, lixisenatide, and tirzepatide, mimic the action of the incretin hormone GLP-1, enhancing insulin secretion and beta cell survival (8-16, 18). They are also used in the management of obesity, where they slow gastric emptying and increase satiety, reducing appetite. The cardioprotective and renal function-improving properties of GLP-1 RA therapy also benefit overweight and obese patients. Several GLP-1 receptor agonists have been shown to reduce body mass index in clinical trials and are approved for the treatment of obesity. However, these drugs are associated with gastrointestinal discomfort, affecting about 50% of patients and significantly impacting their quality of life (Pi-Sunyer X, etal. NEngl JMed 2015 Jul 2;373(1): 11-22; Marre M, et al. Diabet Med2009 Mar 12;26(3):268-78; Nauck M, et al. Diabetes Care 2009 Jan l;32(l):84-90; Garber A, et al. Lancet 2009 Feb;373(9662):473-81; Unger J, et al. Diabetes, ObesMetab 2022 Feb 18;24(2):204-l 1; Buse JB, et al. Lancet 2009 Jul;374(9683):39-47; Russell-Jones D, et al. Diabetologia 2009 Oct 14;52(10):2046-55; Sikirica M V., et al., Diabetes, Metab Syndr Obes 2017 Sep; 10:403-12; Kanoski SE, et al., Neuropharmacology 2012 Apr;62(5-6): 1916-27). Nausea and vomiting are primary reasons for discontinuation of GLP-1 RA therapy, as reported by both physicians and patients. For example, a cross-sectional study revealed nausea and vomiting as the main reasons for discontinuation of GLP-1 RA therapy, reported by both physicians (43.8%) and patients (ranging from 45.4% to 64.4%). In addition, 51.6% of patients considered these to be the most troublesome problems associated with GLP-1RA use (Sikirica M V., et al., Diabetes, Metab Syndr Obes 2017 Sep;10:403-12). A retrospective study indicated a 53.3% discontinuation rate among patients, highlighting the challenges in widespread implementation of this therapy (Divino V, etal. Glucagon-Like Peptide-1 Receptor Agonist Treatment Patterns Among Type 2 Diabetes Patients in Six European Countries. Diabetes Ther 2014 Dec 4;5(2):499-520). The severity of side effects is often dose-related and typically occurs within the first 4-8 weeks of treatment, with higher doses needed for obesity management often exacerbating gastrointestinal issues (Pi-Sunyer X, etal. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med 2015 Jul 2;373(1): 11-22, Nauck M, etal. Diabetes Care 2009 Jan l;32(l):84-90, Davies MJ, et al. JAMA - J Am Med Assoc 2015 Aug 18;314(7):687-99, Kelly AS, et al. N Engl J Med 2020 May 28;382(22):2117-28). Although these side effects are not life-threatening, they significantly impair the quality of life and increase the likelihood of drug discontinuation. Thus, there is an urgent need for more effective chemical compounds that can alleviate the gastrointestinal discomfort associated with GLP-1 RA therapy, especially since treatment may be lifelong depending on the patient's condition. It is an object of the invention to provide methods of reducing GLP-1 receptor agonist induced side effects. It is also an object of the invention to provide methods of treating GLP-1 receptor agonist induced gastrointestinal side effects. Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present disclosure as it existed before the priority date of each claim of this application. Throughout this specification the word “comprise,” or variations such as “comprises” or “comprising,” will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps. BRIEF SUMMARY OF THE INVENTION It has been established by the present invention that administration of homotaurine or a homotaurine analog restores normal drinking and feeding patterns and reduces negative side effects associated with GLP-1 RA therapy, e.g., nausea, vomiting and constipation. Thus, disclosed are methods for reducing one or more gastrointestinal side effects in a subject receiving GLP-1 RA therapy. Where methods of treatment are disclosed herein, also disclosed are compositions for use in such a method of treatment, and specifically compositions comprising homotaurine or a homotaurine analog for use in a method of reducing one or more gastrointestinal side effects in a subject receiving GLP-1 RA therapy. The methods include administering to a subject receiving glucagon-like peptide-1 (GLP-1) receptor agonist (RA) therapy, an amount of homotaurine-like gastrointestinal distressrelieving (HTL-GIDR) composition effective to reduce one or more side effects of GLP-1 RA therapy selected from nausea, vomiting, and constipation. Typically, the subject is undergoing GLP-1 receptor agonist therapy, i.e., the subject is being administered one or more GLP-1 receptor agonists. Homotaurine is generally administered to the subject after the onset of one or more side effects commonly associated with GLP-1 receptor agonist treatment, such as nausea and / or vomiting. In some forms, the HTL-GIDR composition is administered concurrently or in conjunction with one or more GLP-1 receptor agonists, for example, to allow the subject to tolerate a higher dosage of GLP-1 RA therapy than would be possible without the HTL-GIDR composition. Also described is the use of homotaurine-like gastrointestinal distress-relieving (HTL GIDR) compositions for reducing one or more gastrointestinal side effects in subjects undergoing glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy. GLP-1 RAs are widely used for the treatment of various conditions, including diabetes, obesity, and neurodegenerative diseases, but are often associated with undesirable gastrointestinal side effects, such as nausea, vomiting, loss of appetite, weight fluctuations, and constipation. Described is the use of HTL GIDR compositions to mitigate these side effects, allowing for improved patient tolerance and enhanced therapeutic outcomes. In one aspect, the HTL GIDR composition is used to specifically reduce gastrointestinal side effects, such as nausea, vomiting, loss of appetite, weight loss, weight gain, and constipation, which are frequently experienced by patients receiving GLP-1 RA therapy. In some forms, the HTL-GIDR composition includes homotaurine, acamprosate calcium, valiltramiprosate, 3-sulfopropanoic acid or a combination thereof. In some forms, the HTL-GIDR does not include taurine. In some forms, the amount of homotaurine or homotaurine analog in the HTL-GIDR composition is the human equivalent dosage of a dosage sufficient to increase appetite in rats receiving liraglutide. In some forms, the amount of homotaurine or homotaurine analog in the HTL-GIDR composition is the human equivalent dosage of a dosage sufficient to reduce weight loss in rats receiving liraglutide. In some forms, the amount of homotaurine or homotaurine analog in the HTL-GIDR composition is the human equivalent dosage of a dosage sufficient to prevent weight loss in rats receiving liraglutide. In some forms, the amount of homotaurine or homotaurine analog in the HTL-GIDR composition is the human equivalent dosage of a dosage of the HTL-GIDR sufficient to reduce one or more GLP-1 RA therapy induced negative side effects in rats receiving liraglutide. In some forms, the one or more GLP-1 RA therapy induced negative side effects are nausea, vomiting, constipation, or combinations thereof. In some forms, the dosage sufficient to increase appetite in rats receiving liraglutide is able to rescue liraglutide induced abnormal feeding and drinking behavior in rats that had been habituated to drink cherry juice while receiving saline injections. In some forms, the HTL-GIDR is in a unit dose formulation. In some forms, the GLP-1 RA therapy includes administration of any medication whose therapeutic effect is to agonize the GLP1 receptor. In some forms, the GLP-1 RA therapy includes administration of albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, tirzepatide, danuglipron, orforglipron, retatrutide, efpeglenatide, ALT-801, cotadutide, mazdutide, BI 456905, BI 456906, BI 442524, PF-07081532, SAR425899, TTP273, BAT1706, MN-850, APD334, CT-996, CT-388, DA-JC4, DA-CH5, XW003, NNC9204-1706, IMB-2024, SCO-267, NLY01, MK-8521, HM15211, DMB-3115, RG7697, RG7906, RG1067, or combinations thereof. In some forms, the dulaglutide is used at a dosage from about 0.75 mg / week to about 1.5 mg / week when administered via subcutaneous injection. In some forms, the exenatide is used at a dosage from about 10 mg / week to about 20 pg / day when administered via subcutaneous injection. In some forms, the exenatide extended is used at a dosage from about 2 mg / week when administered via subcutaneous injection. In some forms, the liraglutide is used at a dosage from about 0.6 mg / week to about 3 mg / day when administered via subcutaneous injection. In some forms, the lixisenatide is used at a dosage of from about 10 mg / week to about 20 pg / day when administered via subcutaneous injection. In some forms, the semaglutide is used at a dosage of from about 3 mg / week to about 14 mg / day when administered orally. In some froms, the semaglutide is used at a dosage from about 0.25 mg / week to about 1 mg / week when administered via subcutaneous injection. In some forms, the albiglutide is used at a dosage from about 30 mg / week to about 50 mg / week. In some forms, the tirzepatide is used at a dosage from about 2.5 mg / week to about 15 mg / week when administered via subcutaneous injection. In other forms, equivalent effective doses are contemplated when albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, or tirzepatide, or combinations thereof, are administered via other routes of administration. In some forms, the subject is receiving and tolerating a higher dosage of the GLP-1 RA therapy than the subject could tolerate in the absence of the administration of the HTL-GIDR. In some forms, the higher dosage of the GLP-1 RA therapy provides greater therapeutic effect to the subject. In some forms, the subject is receiving the GLP-1 RA therapy as a treatment for cancer, diabetes, neurodegeneration, excess body weight, incipient diabetes, risk of diabetes, or risk of neurodegeneration. In some forms, the subject maintains a higher body weight than the subject would maintain in the absence of the administration of the HTL-GIDR. In general, disclosed are methods for reducing one or more gastrointestinal side effects in a subject receiving glucagon-like peptide-1 (GLP-1) receptor agonist (RA) therapy. The methods include administering to a subject receiving GLP-1 RA therapy an amount of homotaurine-like gastrointestinal distress-relieving (HTL-GIDR) composition effective to reduce side effects of GLP-1 RA therapy, e.g., nausea, vomiting, and constipation. Generally, the HTL-GIDR composition can be homotaurine or a homotaurine analog such as acamprosate calcium, valiltramiprosate, 3-sulfopropanoic acid, or a combination thereof. The HTL-GIDR composition, containing taurine or its analog, is dosed at levels equivalent to dosages effective in increasing appetite and reducing weight loss in rats treated with liraglutide. The HTL-GIDR composition is suitable for restoring normal feeding and drinking behaviors following GLP-1 RA therapy. Additionally, the HTL-GIDR composition helps subjects to tolerate higher doses of various GLP-1 RA therapies, thereby improving the therapeutic effects for conditions such as diabetes, obesity, and neurodegeneration. Additional advantages of the disclosed method and compositions will be set forth in part in the description which follows, and in part will be understood from the description, or can be learned by practice of the disclosed method and compositions. The advantages of the disclosed method and compositions will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed. BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings illustrate several embodiments of the disclosed method and compositions and together with the description, serve to explain the principles of the disclosed method and compositions. Figure 1A is a line graph showing drinking curves per animal per cage monitored over 7 days during liraglutide / saline treatment. Figures 1B-1G are bar graphs of daily drink consumption between treatments. The data in Figures 1A-1G are combined from different experiments performed at different time with animals of the same age (5-6 months), sex and genotype. Liraglutide receiving and GABA drinking animals are drinking strikingly smaller amounts than other treatment groups. Same phenomenon displayed as columns during the first week. Contrarily, liraglutide receiving and taurine drinking animals’ drink intake is comparable to saline treated and water drinking animals. The data were compared using ordinary one-way ANOVA followed by Bonferroni’s multiple comparisons test. The data in Figures 1B-1G are presented as the mean and standard error of the mean. Symbols represent drink consumption per animal per cage, ns, not significant, * p <0.05, *** p <0.001, **** p <0.0001. Figures 2A and 2B are bar graphs showing taurine preference over water of taurine drinking and liraglutide treated (and corresponding control rats) at 24h. Figures 2C and 2D are bar graphs showing cumulative (0-72h) liquid consumptions are shown at 72h time point. Independent of treatment all rats (WT and Wfsl KO animals combined) chose the taurine drink as the first option. Data is presented as the mean and standard error of the mean. The data were compared using two-way ANOVA followed by Bonferroni’s multiple comparisons test. Symbols represent individual drink consumption per animal per cage, ns, not significant, * p <0.05, ** p <0.01, ***p< 0.001. Figures 3A and 3B are line graphs showing food intake (Figure 3A) and drink intake (Figure 3B) monitored over 72 hours during noted treatments. Figures 3C and 3D are bar graphs showing comparison of baseline and 72 h diet and drink consumption per cage per animal after different treatments. The data were compared using two-way ANOVA followed by Bonferroni’s multiple comparisons test. The data in Figures 3C and 3D are presented as the mean and standard error of the mean. Symbols represent mean cage diet and drink consumption per animal (n= 3-6). ns, not significant, * p <0.05, **p <0.01. Figures 4A-4D show diet and drink intake from saline, liraglutide and homotaurine + liraglutide treated animals from cages receiving cherry, cherry + GABA and cherry + taurine drinks (see Table 2). Figures 4A and 4B are line graphs showing diet intake (Figure 4A) and drink intake (Figure 4B) curves monitored over 72 hours during liraglutide, saline and homotaurine + liraglutide treatment. Figures 4C and 4D are bar graphs showing that independent of drink (cherry, cherry + GABA, cherry + taurine) homotaurine administration normalizes drink and diet intake of liraglutide treated WS rats. The data were compared using two-way ANOVA followed by Bonferroni’s multiple comparisons test. The data in Figures 4C and 4D are presented as the mean and standard error of the mean. Symbols represent mean cage diet and drink consumption per animal (n= 9-18). ns, not significant, *** p <0.001, **** p <0.0001. Figures 5A-5C show body weights from saline (n=9), liraglutide (n=18) and homotaurine + liraglutide (n=9) treated animals from cages receiving cherry, cherry + GABA and cherry + taurine drinks (see Table 2). Figure 5A is a line graph of the body weight curve over 72 hours displaying continuous loss of body weight in liraglutide treated animals. Figure 5B is a bar graph comparing the baseline (Oh vs 72h) bodyweight of all animals receiving liraglutide display weight reduction. Figure 5C is a bar graph showing data from the second day (24h vs 72h) homotaurine + liraglutide treated animals the body weight stabilizes whereas in animals receiving liraglutide the body weight continues to decline. The data were compared using two-way ANOVA followed by Bonferroni’s multiple comparisons test. The data in Figures 5B and 5C are presented as the mean and standard error of the mean. Symbols represent individual animals n=9-18 per group, ns, not significant, **** p <0.0001. Figures 6A-6F are bar graphs showing drink (1 / 5 dilution of cherry juice) intake (Figures 6A-6C) and food intake (Figures 6D-6F) of Wistar Hannover rats receiving liraglutide and combination of liraglutide and homotaurine were monitored over a 72-hour period. The graphs compare baseline food and fluid consumption per cage per animal at 24, 48, and 72 hours following the different treatments. Statistical comparisons were performed using two-way ANOVA followed by Bonferroni’s multiple comparisons test. Data are presented as mean ± standard error of the mean (SEM). Symbols represent mean food and fluid consumption per cage per animal (n = 6). ns, not significant; * p <0.05; **p <0.01; *** p <0.001; ****p <0.0001. Figures 7A-7I are bar graphs showing the effects of liraglutide and combination of liraglutide and homotaurine treatments on fecal weight (Figures 7A-7C), stool frequency (Figures 7D-7F), and median stool weight (Figures 7G-7I) of Wistar Hannover rats over a 72-hour period. Animals were drinking 1 / 5 dilution of cherry juice during treatments. Statistical comparisons were performed using a two-tailed parametric t-test. Data are presented as mean ± standard error of the mean (SEM). Symbols represent the mean fecal weight per cage, stool frequency, and median stool weight per animal (n = 6). ns, not significant; * p <0.05; **** p <0.0001. Figure 8A is a line graph showing body weight of Wistar Hannover rats receiving liraglutide and combination of liraglutide and homotaurine was monitored over a 72-hour period. Figure 8B is a bar graph comparing baseline body weight with body weight measured 72 hours after daily treatments with liraglutide or liraglutide combined with homotaurine. Animals were drinking 1 / 5 dilution of cherry juice during treatments. Statistical comparisons were performed using two-way ANOVA followed by Bonferroni’s multiple comparisons test. Data are presented as mean ± standard error of the mean (SEM). Symbols represent the mean body weight per animal (n = 6). ** p <0.01. DETAILED DESCRIPTION OF THE INVENTION The disclosed method and compositions can be understood more readily by reference to the following detailed description of particular embodiments and the Example included therein and to the Figures and their previous and following description. Disclosed are methods and compositions for reducing one or more negative side effects associated with GLP-1 receptor agonist therapy. The disclosed methods are based on the discovery that administration of homotaurine to a subject is effective for reducing negative side effects associated with the GLP-1 receptor agonist treatment such as nausea and vomiting. Thus, disclosed are methods of administering to a subject receiving GLP-1 receptor agonist therapy, an amount of a homotaurine-like gastrointestinal distress relieving (HTL-GIDR) composition. The HTL-GIDR composition contains homotaurine or homotaurine analog in an amount effective to reduce one or more gastrointestinal side effects associated with GLP-1 receptor therapy such as vomiting, nausea, and constipation. Typically, the subject being administered the HTL-GIDR composition is undergoing GLP-1 receptor agonist therapy, i.e., the subject is being administered one or more GLP-1 receptor agonists. Homotaurine is generally administered to the subject after the onset of one or more side effects commonly associated with GLP-1 receptor agonist treatment, such as nausea and / or vomiting. Typically, the HTL-GIDR composition contains taurine or a taurine analog in an amount effective to reduce one or more gastrointestinal side effects associated with GLP-1 receptor therapy such as vomiting, nausea, and constipation. I. Definitions As used herein, the term “negative side effects” or “side effects” refers to unintended, harmful, and / or undesirable, outcomes or consequences arising from the administration or use of a drug, therapy, or medical treatment such as an active agent therapy. A negative side effect may affect the subject’s physical, mental, or emotional health and is typically distinct from the intended therapeutic effects of the treatment. This may include, but is not limited to, symptoms such as discomfort, toxicity, organ dysfunction, allergic reactions, or any other detrimental impact that compromises the subject’s well-being or quality of life. In a non-limiting example, common side effects of GLP-1 RA therapy include, but are not limited to, nausea, vomiting and profuse sweating. As used herein, the term “reduction” when used with regard to side effects, refers to a lessening of the severity of one or more side effects noticeable to the patient or a healthcare worker whose care they are under, or the amelioration of one or more side effects such that the side effects are no longer debilitating or no longer noticeable to the patient. As used herein, “oral,” “enteral”, “enterally”, “orally”, “non-parenteral”, “non-parenterally”, and the like, refer to administration of a compound or composition to an individual by a route or mode along the alimentary canal. Examples of “oral” routes of administration of a composition include, without limitation, swallowing liquid or solid forms of a HTL-GIDR composition from the mouth, administration of a HTL-GIDR composition through a nasojejunal or gastrostomy tube, intraduodenal administration composition, and rectal administration. The term “pharmaceutically acceptable,” as used herein, refers to compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problems or complications commensurate with a reasonable benefit / risk ratio, in accordance with the guidelines of agencies such as the Food and Drug Administration. The term "therapeutic agent" refers to an agent that can be administered to prevent or treat a disease or disorder. Therapeutic agents can be a nucleic acid, a nucleic acid analog, a small molecule, a peptidomimetic, a protein, peptide, carbohydrate or sugar, lipid, or surfactant, or a combination thereof. The terms “incorporated” and “encapsulated” means incorporating, formulating, or otherwise including an agent into and / or onto a composition, regardless of the manner by which the agent or other material is incorporated. As used in the specification and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a pharmaceutical carrier" includes mixtures of two or more such carriers, and the like. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. Ranges can be expressed herein as from "about" one particular value, and / or to "about" another particular value. When such a range is expressed, another embodiment includes-1 from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. It is also understood that when a value is disclosed that “less than or equal to” the value, “greater than or equal to the value” and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value “10” is disclosed the “less than or equal to 10” as well as “greater than or equal to 10” is also disclosed. It is also understood that throughout the application, data is provided in a number of different formats, and that this data, represents endpoints and starting points, and ranges for any combination of the data points. For example, if a particular data point “10” and a particular data point 15 are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units is also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed. Disclosed are the components to be used to prepare the disclosed compositions as well as the compositions themselves to be used within the methods disclosed herein. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds may not be explicitly disclosed, each is specifically contemplated and described herein. For example, if a particular polypeptide is disclosed and discussed and a number of modifications that can be made to a number of polypeptides are discussed, specifically contemplated is each and every combination and permutation of polypeptides and the modifications that are possible unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited each is individually and collectively contemplated meaning combinations, A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are considered disclosed. Likewise, any subset or combination of these is also disclosed. Thus, for example, the sub-group of A-E, B-F, and C-E would be considered disclosed. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the disclosed compositions. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the disclosed methods. II. Methods for Treating Side Effects Associated with GLP-1 Therapy Disclosed are methods of treating GLP-1 RA therapy induced gastrointestinal side effects. The methods are based on the discovery that administration of homotaurine reduces abnormal feeding and drinking behaviors induced by the GLP-1 RA agonist liraglutide, even when the context of nausea is triggered by strongly flavored solutions such as cherry juice, GABA-cherry juice, or taurine-cherry juice (see Figures 4A-4D). Also, as demonstrated in the non-limiting Examples, administration of homotaurine not only improved feeding and drinking behaviors but also stabilized body weight in a murine model (see Figures 5A-5C). Therefore, disclosed are methods of administering an HTL-GIDR composition containing a homotaurine or homotaurine analog in an amount effective to reduce one or more side effects in a subject receiving GLP-1 therapy e.g., liraglutide or semaglutide. A. Homotaurine-like Gastrointestinal Distress-Relieving Compositions The disclosed methods generally include administering to a subject receiving GLP-1 receptor therapy, an amount of a homotaurine-like gastrointestinal distress relieving (HTL-GIDR) composition. The HTL-GIDR composition typically contains homotaurine or an analog thereof, in an amount effective, when administered to a subject receiving GLP-1 therapy, to reduce one or more side effects associated with GLP-1 therapy. In some forms, the HTL-GIDR composition does not contain taurine. 1. Homotaurine and Homotaurine Analogs The HTL-GIDR composition generally contains homotaurine or a homotaurine analog. In some forms, the HTL-GIDR composition contains homotaurine. In some forms, the HTL-GIDR composition contains a homotaurine analog. Suitable homotaurine analogs include, but are not limited to: acamprosate calcium, valiltramiprosate (ALZ-801), 3-sulfopropanoic acid, ethanesulfonic acid, piperidine-4-sulfonic acid, 3-Pyridine sulfonic acid, tauropine, gabamide, N-acetyltaurine, taurine-O-sulfonic acid, and hypotaurine. i. Homotaurine Homotaurine (also known as tramiprosate (INN), 3-amino-1-propanesulfonic acid, or 3-APS) is an orally active and brain penetrant natural sulfonic acid found in various species of marine algae (Martorana, etaL, Frontiers in Aging Neuroscience, 6:254 (2014). Homotaurine is a taurine analog, with an extra carbon in its chain. Homotaurine is also a GABA analog with neuroprotection, anti convulsion and antihypertension effects (Wu S etal., Neuropharmacology, 83:107-17 (2014); Francine Gervais, et al., Neurobiol Aging, 28(4):537-47 (2007); R GFariello, etal. Neurology, 32(3):241-5 (1982). Homotaurine has the chemical formula C3H9NO3S, and is commercially available from multiple suppliers e.g., MedChemExpress (Catalog # HY-14602R and HY14602), R&D Systems (Catalog # 3619), Santa Cruz Biotechnology, Inc. (Catalog #sc-204353), Sigma-Aldrich (Catalog #1000565_USP), BOC Sciences (Catalog #3687-18-1); eMolecules (ID: 534600); and Activate Scientific (Catalog #AS22421). The structure of homotaurine is as follows: Structure I - Homotaurine ii. Acamprosate calcium Acamprosate Calcium is also referred to as 3-(Acetylamino)-1-propanesulfonic acid calcium and Calcium N-acetylhomotaurinate. Acamprosate Calcium is a GABA receptor agonist and glutamatergic systems modulator. Acamprosate calcium is commercially available, for example, from Santa Cruz Animal Health as a salt (Chemical Formula: CioH2oN208S2*Ca; Catalog # sc-210733), Sigma Aldrich (Chemical Formula: CsHioCao.sNC^S; Catalog # BPI 172); MedChemExpress (Catalog # HY-17030 and HY-17030R); Clinivex (Catalog #RCLTRA120000, #RCLSTLA156, #RCLS3C0149, RCLST000021); eMolecules (Catalog #8318657); Santa Cruz Biotechnology, Inc. (Catalog #sc-210733); AstaTech, Inc. (Catalog #T71327). The structure of acamprosate calcium is as follows: J O Structure II - Acamprosate Calcium iii. Valiltramiprosate (ALZ-801) Valiltramiprosate is also referred to as ALZ-801, NRM-8499, homotaurine prodrug, and 3-APS. ALZ-801 is a prodrug of homotaurine, a modified amino acid developed under the names tramiprosate and Alzhemed™. ALZ-801 is converted to homotaurine in vivo but is more easily absorbed and lasts longer in the blood than tramiprosate. ALZ-801 is a potent and orally available small-molecule P-amyloid (AP) anti-oligomer and aggregation inhibitor, valine-conjugated proagent of Tramiprosate with improved PK properties and gastrointestinal tolerability compared with the parent compound, Tramiprosate. ALZ-801 has the chemical formula C8H18N2O4S and is commercially available from MedChemExpress (Catalog # HY-117259) and LKT Labs (Catalog # V014451); eMolecules (ID: 106932048); Amadis Chemical (Catalog # A939029); TargetMol (Catalog # T14199); Lan Pharmatech (Catalog # LAN-B52495). The structure of ALZ-801 is as follows: Structure III - ALZ-801 iv. Ethanesulfonic Acid Ethanesulfonic acid, also known as esylic acid, is a sulfonic acid with the chemical formula CH3CH2SO3H. Its conjugate base is called ethanesulfonate, or esilate when used in pharmaceutical formulations. This compound is a colorless liquid. (Ye and Stringham, J Chromatogr A. 927(1-2): 53-60 (2001)). Ethanesulfonic acid is commercially available from Sigma Aldrich (Catalog # 186260-5G and 186260-25G); SantaCruz Animal Health (Catalog # sc-239864); ThermoFisher Scientific (Catalog # 014891-30); eMolecules (475085); J&H Chemical Co.,ltd (JH707691); Debye Scientific Co., Ltd (DB-053390). The structure of ethanesulfonic acid is as follows: Structure IV: Ethanesulfonic Acid v. Piperidine-4-sulfonic Acid Piperidine-4-sulfonic acid, also known as P4S and is a potent GABA agonist with an IC50 of 0.034 pM for the inhibition of the binding of H-GABA. Piperidine-4-sulfonic Acid has the chemical formula C5H11NO3S and is commercially available from MedChemExpress (Catalog # HY-139116), SantaCruz Animal Health (Catalog # sc-253279), and Sigma Aldrich (Catalog # P9159-25MG and P9159-250MG); J&H Chemical Co., Ltd (Catalog # JH456533); Santa Cruz Biotechnology, Inc. (Catalog # sc-253279); eMolecules (ID: 593898). The structure of piperidine-4-sulfonic acid is as follows: Structure IV: Piperidine-4-sulfonic Acid vi. 3-Pyridine Sulfonic Acid 3-Pyridine Sulfonic Acid has the chemical formula, C5H4NO3S, and is commercially available from Sigma-Aldrich (Catalog # 82820-25G and 82820-100G), ThermoFisher Scientific (Catalog# 131921000), VWR (Catalog #AAA13101-36, AAA13101-22, and AAA13101-14) and SantaCruz Animal Health (Catalog # sc-238626 and sc-238626A). The structure of 3-Pyridine Sulfonic Acid is as follows: Structure VI: 3-Pyridine Sulfonic Acid vii. Tauropine Tauropine is a derivative of L-alanine having a 2-sulfoethyl group attached to the alphanitrogen. It is a D-alanine derivative, a D-alpha-amino acid and an organosulfonic acid. It is functionally related to taurine and is a conjugate acid of a tauropinate. Tauropine has the chemical formula C5H11NO5S, and is commercially available from Starshine Chemical (Catalog # 2023-05-26B3571), RR Scientific (Catalog # R189429), Chemenu Inc. (Catalog # CM601758), AA Blocks (Catalog # AA00D157), EvitaChem (Catalog # evt-1563815), Sinfoo Biotech (Catalog # S047556), BLD Pharm (Catalog # BD714334), A2B Chern (Catalog # AG07911), and J&H Chemical Co., Ltd (Catalog # JH261612). The structure of tauropine is as follows: G Structure VII - Tauropine viii. Gabamide Gabamide is also known as 4-aminobutanamide and 4-aminobutyramide and has the chemical formula C4H10N2O. Gabamide is commercially available, for example, from BOC Sciences (Catalog # 3251-08-9), CymitQuimica (Catalog # CQ_3251-08-9), RR Scientific (Catalog # R2532180). Gabamide has the following structure: Structure VIII - Gabamide ix. 3-sulfopropanoic acid 3-sulfopropanoic acid is also known as 44826-45-1, and 6306-41-8. 3-sulfopropanoic acid has the chemical formula C3H6O5S and the molecular weight 154.14 g / mol. 3-sulfopropanoic acid is commercially available, for example, from eMolecules (Catalog #67909832); J&H Chemical Co. Ltd (Catalog #JH302679); BLD Pharm (Catalog #BD01044758); TargetMol (Catalog #TN7246). 3-sulfopropanoic acid has the following structure: ,O V. O Structure IX - 3-sulfopropanoic acid x. N-acetyltaurine N-acetyltaurine is also known as acetyltaurine, 19213-70-8, 2-acetamidoethanesulfonic acid, and acetyltaurinate. N-acetyltaurine has the chemical formula C4H9NO4S and the molecular weight 167.19 g / mol. N-acetyltaurine is commercially available, for example, from BLD Pharm (Catalog #BD01221802); Hairui Chemical (Catalog #HR165671); eMolecules (ID: 96326850); eNovation Chemicals (Catalog # Y3196035). N-acetyltaurine has the following structure: Structure X - N-acetyltaurine xi. Taurine-O-sulfonic acid Taurine-O-sulfonic acid is also known as 1235825-84-9, ammonium 2-aminoethane-l,l-disulfonic acid hydrate, taurine sulfonic acid, SCHEMBL5158836, and 2-aminoethane-l,l-disulfonic acid. Taurine-O-sulfonic acid has the chemical formula C2H7NO6S2, and the molecular weight 205.22 g / mol. Taurine-O-sulfonic acid is commercially available, for example, from eMolecules (Catalog #303167982); BLD Pharm (Catalog #BD01146244); and EvitaChem (Catalog #evt-1816445). Taurine-O-sulfonic acid has the following structure: Structure XI - Taurine-O-sulfonic acid xii. Hypotaurine Hypotaurine is also known as 2-aminoethanesulfmic acid, 300-84-5, 2-aminoethylsulfinic acid, and 2-aminoethanesulfmic acid. Hypotaurine has the chemical formula C2H7NO2S and the molecular weight 109.15 g / mol. Hypotaurine is commercially available, for example, from Sigma-Aldrich (Catalog # Hl384); eMolecules (Catalog # 538970); Santa Cruz Biotechnology, Inc. (Catalog # sc-204005); BOC Sciences (Catalog # 300-84-5). Hypotaurine has the following structure: O Structure XII - Hypotaurine 2. Delivery Vehicles The HTL-GIDR composition is formulated to include homotaurine or a homotaurine analog and a pharmaceutically acceptable carrier in the same admixture, or in separate formulations. The HTL-GIDR composition is formulated to be administered separately from the GLP-1 receptor agonist, preferably after the onset of one or more symptoms associated with the administration of GLP-1 receptor agonist. In some forms, the homotaurine or homotaurine analog, and optionally additional therapeutic, prophylactic, and / or diagnostic agents are administered and taken up into the cells of a subject with the aid of a delivery vehicle. Appropriate delivery vehicles for the disclosed compositions are known in the art and can be selected to suit the particular formulation. For example, in some forms, the composition is incorporated into or encapsulated by a nanoparticle, microparticle, micelle, synthetic lipoprotein particle, or carbon nanotube. For example, the compositions can be incorporated into a vehicle such as polymeric microparticles, which provide controlled release of the homotaurine or homotaurine analog. In some forms, release of the homotaurine or homotaurine analog and / or additional therapeutic, prophylactic, and / or diagnostic agents is controlled by diffusion of the active compositions out of the microparticles and / or degradation of the polymeric particles by hydrolysis and / or enzymatic degradation. Suitable polymers include ethylcellulose and other natural or synthetic cellulose derivatives. Polymers which are slowly soluble and form a gel in an aqueous environment, such as hydroxypropyl methylcellulose or polyethylene oxide may also be suitable as materials for drug containing microparticles. Other polymers include, but are not limited to, poly anhydrides, poly (ester anhydrides), polyhydroxy acids, such as polylactide (PLA), polyglycolide (PGA), poly(lactide-co-glycolide) (PLGA), poly-3-hydroxybutyrate (PHB) and copolymers thereof, poly-4-hydroxybutyrate (P4HB) and copolymers thereof, polycaprolactone and copolymers thereof, and combinations thereof. 3. Formulations The HTL-GIDR composition can include one or more pharmaceutically acceptable additives. Examples of commonly used additives include stabilizers, solubilizers, surfactants, 18 buffers, antioxidants, preservatives, isotonic agents, extenders, lubricants, emulsifiers, suspending agents, trace components and carriers. Examples include viscous agents, inert diluents, fillers, disintegrants, binders, wetting agents, lubricants, antibacterial agents, chelating agents, and combinations thereof. Such compositions include diluents sterile water, buffered saline of various buffer content (e.g., Tris-HCl, acetate, phosphate), pH and ionic strength and optionally additives such as detergents and solubilizing agents (e.g., TWEEN® 20, TWEEN® 80 also referred to as polysorbate 20 or 80), anti-oxidants (e.g., ascorbic acid, sodium metabisulfite), and preservatives (e.g., Thimersol, benzyl alcohol) and bulking substances (e.g., lactose, mannitol). Examples of non-aqueous solvents or vehicles are propylene glycol, polyethylene glycol, vegetable oils, such as olive oil and corn oil, gelatin, and injectable organic esters such as ethyl oleate. The formulations may be lyophilized and redissolved / resuspended immediately before use. i. Parenteral Formulations The HTL-GIDR compositions described herein (i.e., the composition containing homotaurine or homotaurine analog (s)) can be formulated for parenteral administration. For example, parenteral administration may include administration to a patient intravenously (IV), intraperitoneally (IP), intramuscularly (IM), subcutaneously (SC), by injection, or by infusion. In some forms, the HTL-GIDR composition can be delivered via intravenous (IV), intraperitoneal (IP) and subcutaneous (SC) administration. In some forms, when the HTL-GIDR composition is delivered intravenously, intraperitoneally, or subcutaneously, via injection or infusion, the daily dose can be much lower, for example, up to 5 times, compared with daily oral minimal or maximal doses due to the improved bioavailability of the HTL-GIDR composition when delivered via these routes. In some forms, when the HTL-GIDR composition is delivered intravenously, intraperitoneally, or subcutaneously, via injection or infusion, the daily dose can be 2 times, 3 times, 4 times, or 5 times, compared to the daily oral minimal dose or maximal dose. For example, Olive and colleagues demonstrated that calcium acamprosate and homotaurine can be delivered intraperitoneally (Olive etaL, “Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release”, Eur J Pharmacol., 437(1-2):55-61). In another example, Gervais and colleagues demonstrated that tramiprosate can be delivered subcutaneously (Gervais et al., “Targeting soluble Abeta peptide with Tramiprosate for the treatment of brain amyloidosis”, Neurobiol Aging, 28(4):537-47 (2007)). Parenteral formulations can be prepared as aqueous compositions using techniques is known in the art. Typically, such compositions can be prepared as injectable formulations, for example, solutions or suspensions; solid forms suitable for using to prepare solutions or suspensions upon the addition of a reconstitution medium prior to injection; emulsions, such as water-in-oil (w / o) emulsions, oil-in-water (o / w) emulsions, and microemulsions thereof, liposomes, or emulsomes. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, one or more polyols (e.g., glycerol, propylene glycol, and liquid polyethylene glycol), oils, such as vegetable oils (e.g., peanut oil, com oil, sesame oil, etc.), and combinations thereof. The proper fluidity can be maintained, for example, by the use of a coating, such as lecithin, by the maintenance of the required particle size in the case of dispersion and / or by the use of surfactants. In many cases, it will be preferable to include isotonic agents, for example, sugars or sodium chloride. Solutions and dispersions of the active compounds as the free acid or base or pharmacologically acceptable salts thereof can be prepared in water or another solvent or dispersing medium suitably mixed with one or more pharmaceutically acceptable excipients including, but not limited to, surfactants, dispersants, emulsifiers, pH modifying agents, viscosity modifying agents, and combination thereof. Suitable surfactants may be anionic, cationic, amphoteric or nonionic surface-active agents. Suitable anionic surfactants include, but are not limited to, those containing carboxylate, sulfonate and sulfate ions. Examples of anionic surfactants include sodium, potassium, ammonium of long chain alkyl sulfonates and alkyl aryl sulfonates such as sodium dodecylbenzene sulfonate; dialkyl sodium sulfosuccinates, such as sodium dodecylbenzene sulfonate; dialkyl sodium sulfosuccinates, such as sodium bis-(2-ethylthioxyl)-sulfosuccinate; and alkyl sulfates such as sodium lauryl sulfate. Cationic surfactants include, but are not limited to, quaternary ammonium compounds such as benzalkonium chloride, benzethonium chloride, cetrimonium bromide, stearyl dimethylbenzyl ammonium chloride, polyoxyethylene and coconut amine. Examples of nonionic surfactants include ethylene glycol monostearate, propylene glycol myristate, glyceryl monostearate, glyceryl stearate, polyglyceryl-4-oleate, sorbitan acylate, sucrose acylate, PEG-150 laurate, PEG-400 monolaurate, polyoxyethylene monolaurate, polysorbates, polyoxyethylene octylphenylether, PEG-1000 cetyl ether, polyoxyethylene tridecyl ether, polypropylene glycol butyl ether, Poloxamer® 401, stearoyl monoisopropanolamide, and polyoxyethylene hydrogenated tallow amide. Examples of amphoteric surfactants include sodium N-dodecyl-.beta.-alanine, sodium N-lauryl-.beta.-iminodipropionate, myristoamphoacetate, lauryl betaine and lauryl sulfobetaine. The formulation can contain a preservative to prevent the growth of microorganisms. Suitable preservatives include, but are not limited to, parabens, chlorobutanol, phenol, sorbic acid, and thimerosal. The formulation may also contain an antioxidant to prevent degradation of the active agent(s). The formulation is typically buffered to a pH of 3-8 for parenteral administration upon reconstitution. Suitable buffers include, but are not limited to, phosphate buffers, acetate buffers, and citrate buffers. Water-soluble polymers are often used in formulations for parenteral administration. Suitable water-soluble polymers include, but are not limited to, polyvinylpyrrolidone, dextran, carboxymethylcellulose, and polyethylene glycol. Sterile injectable solutions can be prepared by incorporating the active compounds in the required amount in the appropriate solvent or dispersion medium with one or more of the excipients listed above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the various sterilized active ingredients into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those listed above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum-drying and freeze-drying techniques which yield a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof. The powders can be prepared in such a manner that the particles are porous in nature, which can increase dissolution of the particles. Methods for making porous particles are well known in the art. The parenteral formulations described herein can be formulated for controlled release including immediate release, delayed release, extended release, pulsatile release, and combinations thereof. a. Nano- and microparticles For parenteral administration, the HTL-GIDR compositions and optionally, one or more additional active agents, can be incorporated into microparticles, nanoparticles, or combinations thereof that provide controlled release of the compounds and / or one or more additional active agents. In forms wherein the formulations contain more agents, the agents can be formulated for the same type of controlled release (e.g., delayed, extended, immediate, or pulsatile) or the agents can be independently formulated for different types of release (e.g., immediate and delayed, immediate and extended, delayed and extended, delayed and pulsatile, etc.). For example, HTL-GIDR compositions and / or one or more additional active agents can be incorporated into polymeric microparticles, which provide controlled release of the drug(s). Release of the agent(s) is controlled by diffusion of the agent(s) out of the microparticles and / or degradation of the polymeric particles by hydrolysis and / or enzymatic degradation. Suitable polymers include ethylcellulose and other natural or synthetic cellulose derivatives. Polymers, which are slowly soluble and form a gel in an aqueous environment, such as hydroxypropyl methylcellulose or polyethylene oxide, can also be suitable as materials for drug containing microparticles. Other polymers include, but are not limited to, polyanhydrides, poly(ester anhydrides), polyhydroxy acids, such as polylactide (PLA), polyglycolide (PGA), poly(lactide-co-glycolide) (PLGA), poly-3-hydroxybutyrate (PHB) and copolymers thereof, poly-4-hydroxybutyrate (P4HB) and copolymers thereof, polycaprolactone and copolymers thereof, and combinations thereof. Alternatively, the agent(s) can be incorporated into microparticles prepared from materials which are insoluble in aqueous solution or slowly soluble in aqueous solution but are capable of degrading within the GI tract by means including enzymatic degradation, surfactant action of bile acids, and / or mechanical erosion. As used herein, the term “slowly soluble in water” refers to materials that are not dissolved in water within a period of 30 minutes. Preferred examples include fats, fatty substances, waxes, wax-like substances and mixtures thereof. Suitable fats and fatty substances include fatty alcohols (such as lauryl, myristyl stearyl, cetyl or cetostearyl alcohol), fatty acids and derivatives, including but not limited to fatty acid esters, fatty acid glycerides (mono-, di- and tri-glycerides), and hydrogenated fats. Specific examples include, but are not limited to hydrogenated vegetable oil, hydrogenated cottonseed oil, hydrogenated castor oil, hydrogenated oils available under the trade name Sterotex®, stearic acid, cocoa butter, and stearyl alcohol. Suitable waxes and wax-like materials include natural or synthetic waxes, hydrocarbons, and normal waxes. Specific examples of waxes include beeswax, glycowax, castor wax, carnauba wax, paraffins and candelilla wax. As used herein, a wax-like material is defined as any material, which is normally solid at room temperature and has a melting point of from about 30 to 300°C. In some cases, it may be desirable to alter the rate of water penetration into the microparticles. To this end, rate-controlling (wicking) agents can be formulated along with the fats or waxes listed above. Examples of rate-controlling materials include certain starch derivatives (e.g., waxy maltodextrin and drum dried corn starch), cellulose derivatives (e.g., hydroxypropylmethyl-cellulose, hydroxypropylcellulose, methylcellulose, and carboxymethylcellulose), alginic acid, lactose and talc. Additionally, a pharmaceutically acceptable surfactant (for example, lecithin) may be added to facilitate the degradation of such microparticles. Proteins, which are water insoluble, such as zein, can also be used as materials for the formation of agent containing microparticles. Additionally, proteins, polysaccharides and combinations thereof, which are water-soluble, can be formulated with agent into microparticles and subsequently cross-linked to form an insoluble network. For example, cyclodextrins can be complexed with individual agent molecules and subsequently cross-linked. b. Method of making Nano- and Microparticles Encapsulation or incorporation of agent into carrier materials to produce agent-containing microparticles can be achieved through known pharmaceutical formulation techniques. In the case of formulation in fats, waxes or wax-like materials, the carrier material is typically heated above its melting temperature and the agent is added to form a mixture comprising agent particles suspended in the carrier material, agent dissolved in the carrier material, or a mixture thereof. Microparticles can be subsequently formulated through several methods including, but not limited to, the processes of congealing, extrusion, spray chilling or aqueous dispersion. In a preferred process, wax is heated above its melting temperature, agent is added, and the molten wax-agent mixture is congealed under constant stirring as the mixture cools. Alternatively, the molten wax-agent mixture can be extruded and spheronized to form pellets or beads. These processes are known in the art. For some carrier materials it may be desirable to use a solvent evaporation technique to produce agent-containing microparticles. In this case agent and carrier material are co-dissolved in a mutual solvent and microparticles can subsequently be produced by several techniques including, but not limited to, forming an emulsion in water or other appropriate media, spray drying or by evaporating off the solvent from the bulk solution and milling the resulting material. In some forms, agent in a particulate form is homogeneously dispersed in a waterinsoluble or slowly water soluble material. To minimize the size of the agent particles within the composition, the agent powder itself may be milled to generate fine particles prior to formulation. The process of jet milling, known in the pharmaceutical art, can be used for this purpose. In some forms drug in a particulate form is homogeneously dispersed in a wax or wax like substance by heating the wax or wax like substance above its melting point and adding the drug particles while stirring the mixture. In this case a pharmaceutically acceptable surfactant may be added to the mixture to facilitate the dispersion of the drug particles. The particles can also be coated with one or more modified release coatings. Solid esters of fatty acids, which are hydrolyzed by lipases, can be spray coated onto microparticles or drug particles. Zein is an example of a naturally water-insoluble protein. It can be coated onto drug containing microparticles or drug particles by spray coating or by wet granulation techniques. In addition to naturally water-insoluble materials, some substrates of digestive enzymes can be treated with cross-linking procedures, resulting in the formation of non-soluble networks. Many 23 methods of cross-linking proteins, initiated by both chemical and physical means, have been reported. One of the most common methods to obtain cross-linking is the use of chemical crosslinking agents. Examples of chemical cross-linking agents include aldehydes (gluteraldehyde and formaldehyde), epoxy compounds, carbodiimides, and genipin. In addition to these cross-linking agents, oxidized and native sugars have been used to cross-link gelatin. Cross-linking can also be accomplished using enzymatic means; for example, transglutaminase has been approved as a GRAS substance for cross-linking seafood products. Finally, cross-linking can be initiated by physical means such as thermal treatment, UV irradiation and gamma irradiation. To produce a coating layer of cross-linked protein surrounding drug containing microparticles or drug particles, a water-soluble protein can be spray coated onto the microparticles and subsequently cross-linked by the one of the methods described above. Alternatively, drug-containing microparticles can be microencapsulated within protein by coacervation-phase separation (for example, by the addition of salts) and subsequently crosslinked. Some suitable proteins for this purpose include gelatin, albumin, casein, and gluten. Polysaccharides can also be cross-linked to form a water-insoluble network. For many polysaccharides, this can be accomplished by reaction with calcium salts or multivalent cations, which cross-link the main polymer chains. Pectin, alginate, dextran, amylose and guar gum are subject to cross-linking in the presence of multivalent cations. Complexes between oppositely charged polysaccharides can also be formed; pectin and chitosan, for example, can be complexed via electrostatic interactions. ii. Enteral Formulations Suitable oral dosage forms include tablets, capsules, solutions, suspensions, syrups, and lozenges. Tablets can be made using compression or molding techniques well known in the art. Gelatin or non-gelatin capsules can be prepared as hard or soft capsule shells, which can encapsulate liquid, solid, and semi-solid fill materials, using techniques well known in the art. Formulations may be prepared using a pharmaceutically acceptable carrier. As generally used herein “carrier” includes, but is not limited to, diluents, preservatives, binders, lubricants, disintegrators, swelling agents, fillers, stabilizers, and combinations thereof. Carrier also includes all components of the coating composition, which may include plasticizers, pigments, colorants, stabilizing agents, and glidants. Examples of suitable coating materials include, but are not limited to, cellulose polymers such as cellulose acetate phthalate, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate and hydroxypropyl methylcellulose acetate succinate; polyvinyl acetate phthalate, acrylic acid polymers and copolymers, and methacrylic resins that are 24 commercially available under the trade name EUDRAGIT® (Roth Pharma, Westerstadt, Germany), zein, shellac, and polysaccharides. Additionally, the coating material may contain conventional carriers such as plasticizers, pigments, colorants, glidants, stabilization agents, pore formers and surfactants. “Diluents”, also referred to as "fillers," are typically necessary to increase the bulk of a solid dosage form so that a practical size is provided for compression of tablets or formation of beads and granules. Suitable diluents include, but are not limited to, dicalcium phosphate dihydrate, calcium sulfate, lactose, sucrose, mannitol, sorbitol, cellulose, microcrystalline cellulose, kaolin, sodium chloride, dry starch, hydrolyzed starches, pregelatinized starch, silicone dioxide, titanium oxide, magnesium aluminum silicate and powdered sugar. “Binders” are used to impart cohesive qualities to a solid dosage formulation, and thus ensure that a tablet or bead or granule remains intact after the formation of the dosage forms. Suitable binder materials include, but are not limited to, starch, pregelatinized starch, gelatin, sugars (including sucrose, glucose, dextrose, lactose and sorbitol), polyethylene glycol, waxes, natural and synthetic gums such as acacia, tragacanth, sodium alginate, cellulose, including hydroxypropylmethylcellulose, hydroxypropylcellulose, ethylcellulose, and veegum, and synthetic polymers such as acrylic acid and methacrylic acid copolymers, methacrylic acid copolymers, methyl methacrylate copolymers, aminoalkyl methacrylate copolymers, polyacrylic acid / polymethacrylic acid and polyvinylpyrrolidone. “Lubricants” are used to facilitate tablet manufacture. Examples of suitable lubricants include, but are not limited to, magnesium stearate, calcium stearate, stearic acid, glycerol behenate, polyethylene glycol, talc, and mineral oil. “Disintegrants” are used to facilitate dosage form disintegration or "breakup" after administration, and generally include, but are not limited to, starch, sodium starch glycolate, sodium carboxymethyl starch, sodium carboxymethylcellulose, hydroxypropyl cellulose, pregelatinized starch, clays, cellulose, alginine, gums or cross-linked polymers, such as crosslinked PVP (Polyplasdone® XL from GAF Chemical Corp). “Stabilizers” are used to inhibit or retard drug decomposition reactions, which include, by way of example, oxidative reactions. Suitable stabilizers include, but are not limited to, antioxidants, butylated hydroxytoluene (BHT); ascorbic acid, its salts and esters; Vitamin E, tocopherol and its salts; sulfites such as sodium metabisulphite; cysteine and its derivatives; citric acid; propyl gallate, and butylated hydroxyanisole (BHA). Oral dosage forms, such as capsules, tablets, solutions, and suspensions, can for formulated for controlled release. For example, the immunogenic compositions, and optionally one or more additional active agents can be formulated into nanoparticles, microparticles, and combinations thereof, and encapsulated in a soft or hard gelatin or non-gelatin capsule or dispersed in a dispersing medium to form an oral suspension or syrup. The particles can be formed of the agent and a controlled release polymer or matrix. Alternatively, the agent particles can be coated with one or more controlled release coatings prior to incorporation into the finished dosage form. In some forms, the HTL-GIDR compositions, and optionally one or more additional active agents are dispersed in a matrix material, which gels or emulsifies upon contact with an aqueous medium, such as physiological fluids. In the case of gels, the matrix swells entrapping the active agents, which are released slowly over time by diffusion and / or degradation of the matrix material. Such matrices can be formulated as tablets or as fill materials for hard and soft capsules. In some forms, the one or more compounds, and optional one or more additional active agents are formulated into a sold oral dosage form, such as a tablet or capsule, and the solid dosage form is coated with one or more controlled release coatings, such as a delayed release coatings or extended-release coatings. The coating or coatings may also contain the compounds and / or additional active agents. a. Extended-release dosage forms The extended-release formulations are generally prepared as diffusion or osmotic systems, which are known in the art. A diffusion system typically consists of two types of devices, a reservoir, and a matrix, and is well known and described in the art. The matrix devices are generally prepared by compressing the agent with a slowly dissolving polymer carrier into a tablet form. The three major types of materials used in the preparation of matrix devices are insoluble plastics, hydrophilic polymers, and fatty compounds. Plastic matrices include, but are not limited to, methyl acrylate-methyl methacrylate, polyvinyl chloride, and polyethylene. Hydrophilic polymers include, but are not limited to, cellulosic polymers such as methyl and ethyl cellulose, hydroxyalkylcelluloses such as hydroxypropyl-cellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, and Carbopol® 934, polyethylene oxides and mixtures thereof. Fatty compounds include, but are not limited to, various waxes such as carnauba wax and glyceryl tristearate and wax-type substances including hydrogenated castor oil or hydrogenated vegetable oil, or mixtures thereof. In some forms, the plastic material is a pharmaceutically acceptable acrylic polymer, including but not limited to, acrylic acid and methacrylic acid copolymers, methyl methacrylate, methyl methacrylate copolymers, ethoxyethyl methacrylates, cyanoethyl methacrylate, aminoalkyl methacrylate copolymer, poly(acrylic acid), poly(methacrylic acid), methacrylic acid alkylamine copolymer poly(methyl methacrylate), poly(methacrylic acid)(anhydride), polymethacrylate, polyacrylamide, poly(methacrylic acid anhydride), and glycidyl methacrylate copolymers. In some forms, the acrylic polymer is comprised of one or more ammonio methacrylate copolymers. Ammonio methacrylate copolymers are well known in the art and are described in NF XVII as fully polymerized copolymers of acrylic and methacrylic acid esters with a low content of quaternary ammonium groups. In some forms, the acrylic polymer is an acrylic resin lacquer such as that which is commercially available from Rohm Pharma under the tradename EUDRAGIT t®. In some forms, the acrylic polymer comprises a mixture of two acrylic resin lacquers commercially available from Rohm Pharma under the tradenames EUDRAGIT® RL30D and EUDRAGIT ® RS30D, respectively. EUDRAGIT® RL30D and EUDRAGIT ® RS30D are copolymers of acrylic and methacrylic esters with a low content of quaternary ammonium groups, the molar ratio of ammonium groups to the remaining neutral (meth)acrylic esters being 1:20 in EUDRAGIT ® RL30D and 1:40 in EUDRAGIT® RS30D. The mean molecular weight is about 150,000. EUDRAGIT ® S-100 and EUDRAGIT ® L-100 are also preferred. The code designations RL (high permeability) and RS (low permeability) refer to the permeability properties of these agents. EUDRAGIT ® RL / RS mixtures are insoluble in water and in digestive fluids. However, multi-particulate systems formed to include the same are swellable and permeable in aqueous solutions and digestive fluids. The polymers described above such as EUDRAGIT ® RL / RS may be mixed in any desired ratio in order to ultimately obtain a sustained-release formulation having a desirable dissolution profile. Desirable sustained release multi-particulate systems may be obtained, for instance, from 100% EUDRAGIT® RL, 50% EUDRAGIT® RL and 50% EUDRAGIT t® RS, and 10% EUDRAGIT® RL and 90% EUDRAGIT® RS. One skilled in the art will recognize that other acrylic polymers may also be used, such as, for example, EUDRAGIT® L. Alternatively, extended-release formulations can be prepared using osmotic systems or by applying a semi-permeable coating to the dosage form. In the latter case, the desired agent release profile can be achieved by combining low permeable and high permeable coating materials in suitable proportion. The devices with different agent release mechanisms described above can be combined in a final dosage form comprising single or multiple units. Examples of multiple units include, but are not limited to, multilayer tablets and capsules containing tablets, beads, or granules. An immediate release portion can be added to the extended-release system by means of either applying an immediate release layer on top of the extended release core using a coating or compression process or in a multiple unit system such as a capsule containing extended and immediate release beads. Extended-release tablets containing hydrophilic polymers are prepared by techniques commonly known in the art such as direct compression, wet granulation, or dry granulation. Their formulations usually incorporate polymers, diluents, binders, and lubricants as well as the active pharmaceutical ingredient. The usual diluents include inert powdered substances such as starches, powdered cellulose, especially crystalline and microcrystalline cellulose, sugars such as fructose, mannitol and sucrose, grain flours and similar edible powders. Typical diluents include, for example, various types of starch, lactose, mannitol, kaolin, calcium phosphate or sulfate, inorganic salts such as sodium chloride and powdered sugar. Powdered cellulose derivatives are also useful. Typical tablet binders include substances such as starch, gelatin, and sugars such as lactose, fructose, and glucose. Natural and synthetic gums, including acacia, alginates, methylcellulose, and polyvinylpyrrolidone can also be used. Polyethylene glycol, hydrophilic polymers, ethylcellulose and waxes can also serve as binders. A lubricant is necessary in a tablet formulation to prevent the tablet and punches from sticking in the die. The lubricant is chosen from such slippery solids as talc, magnesium and calcium stearate, stearic acid, and hydrogenated vegetable oils. Extended-release tablets containing wax materials are generally prepared using methods known in the art such as a direct blend method, a congealing method, and an aqueous dispersion method. In the congealing method, the agent is mixed with a wax material and either spray-congealed or congealed and screened and processed. b. Delayed release dosage forms Delayed release formulations can be created by coating a solid dosage form with a polymer film, which is insoluble in the acidic environment of the stomach, and soluble in the neutral environment of the small intestine. The delayed release dosage units can be prepared, for example, by coating an agent or an agent-containing composition with a selected coating material. The agent-containing composition may be, e.g., a tablet for incorporation into a capsule, a tablet for use as an inner core in a "coated core" dosage form, or a plurality of agent-containing beads, particles, or granules, for incorporation into either a tablet or capsule. Preferred coating materials include bioerodible, gradually hydrolyzable, gradually water-soluble, and / or enzymatically degradable polymers, and may be conventional "enteric" polymers. Enteric polymers, as will be appreciated by those skilled 28 in the art, become soluble in the higher pH environment of the lower gastrointestinal tract or slowly erode as the dosage form passes through the gastrointestinal tract, while enzymatically degradable polymers are degraded by bacterial enzymes present in the lower gastrointestinal tract, particularly in the colon. Suitable coating materials for effecting delayed release include, but are not limited to, cellulosic polymers such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose acetate succinate, hydroxypropylmethyl cellulose phthalate, methylcellulose, ethyl cellulose, cellulose acetate, cellulose acetate phthalate, cellulose acetate trimellitate and carboxymethylcellulose sodium; acrylic acid polymers and copolymers, preferably formed from acrylic acid, methacrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate and / or ethyl methacrylate, and other methacrylic resins that are commercially available under the tradename Eudragit® (Rohm Pharma; Westerstadt, Germany), including EUDRAGIT® L30D-55 and L100-55 (soluble at pH 5.5 and above), EUDRAGIT® L-100 (soluble at pH 6.0 and above), EUDRAGIT® S (soluble at pH 7.0 and above, as a result of a higher degree of esterification), and EUDRAGITS® NE, RL and RS (water-insoluble polymers having different degrees of permeability and expandability); vinyl polymers and copolymers such as polyvinyl pyrrolidone, vinyl acetate, vinylacetate phthalate, vinylacetate crotonic acid copolymer, and ethylene-vinyl acetate copolymer; enzymatically degradable polymers such as azo polymers, pectin, chitosan, amylose and guar gum; zein and shellac. Combinations of different coating materials may also be used. Multi-layer coatings using different polymers may also be applied. The preferred coating weights for particular coating materials may be readily determined by those skilled in the art by evaluating individual release profiles for tablets, beads and granules prepared with different quantities of various coating materials. It is the combination of materials, method and form of application that produce the desired release characteristics, which one can determine only from the clinical studies. The coating composition may include conventional additives, such as plasticizers, pigments, colorants, stabilizing agents, glidants, etc. A plasticizer is normally present to reduce the fragility of the coating and will generally represent about 10 wt. % to 50 wt. % relative to the dry weight of the polymer. Examples of typical plasticizers include polyethylene glycol, propylene glycol, triacetin, dimethyl phthalate, diethyl phthalate, dibutyl phthalate, dibutyl sebacate, triethyl citrate, tributyl citrate, triethyl acetyl citrate, castor oil and acetylated monoglycerides. A stabilizing agent is preferably used to stabilize particles in the dispersion. Typical stabilizing agents are nonionic emulsifiers such as sorbitan esters, polysorbates and polyvinylpyrrolidone. Glidants are recommended to reduce sticking effects during film formation and drying and will generally represent approximately 25 wt. % to 100 wt. % of the polymer weight in the coating solution. One effective glidant is talc. Other glidants such as magnesium stearate and glycerol monostearates may also be used. Pigments such as titanium dioxide may also be used. Small quantities of an anti-foaming agent, such as a silicone (e.g., simethicone), may also be added to the coating composition. B. Methods of Treatment The terms “high,” “higher,” “increases,” “elevates,” or “elevation” refer to increases above basal levels, e.g., as compared to a control. The terms “low,” “lower,” “reduces,” or “reduction” refer to decreases below basal levels, e.g., as compared to a control. The term “inhibit” means to reduce or decrease in activity or expression. This can be a complete inhibition of activity or expression, or a partial inhibition. Inhibition can be compared to a control or to a standard level. Inhibition can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64,65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100%. The term “in need of treatment” as used herein refers to a judgment made by a caregiver (e.g., physician, nurse, nurse practitioner, or individual in the case of humans; veterinarian in the case of animals, including non-human mammals) that a subject requires or will benefit from treatment. This judgment is made based on a variety of factors that are in the realm of a care giver's expertise, but that include the knowledge that the subject is ill, or will be ill, as the result of a condition that is treatable by the disclosed compounds. The terms “treating” and “retarding development of’ a disease, disorder, or condition occurring in an animal which has or may be predisposed to the disease, disorder and / or condition mean inhibiting the disease, disorder or condition, e.g., impeding its progress; and relieving the disease, disorder, or condition, e.g., causing regression of the disease, disorder and / or condition. Treating the disease or condition includes ameliorating at least one symptom of the particular disease or condition, even if the underlying pathophysiology is not affected, such as treating the pain of a subject by administration of an analgesic agent even though such agent does not treat the cause of the pain. In some forms, the animal has been diagnosed with the disease or disorder. In other forms, the animal has not yet been diagnosed as having the disease or disorder. The terms “preventing” and “preventing development of’ used in the context of a disease, disorder, or condition in an animal mean inhibiting the initiation or development of the disease, disorder or condition, e.g., stopping the animal from developing the disease, disorder or condition, or impeding its progress; and / or preventing the advancement or continuation of at least one symptom of the particular disease or condition, even if the underlying pathophysiology is not affected, such as preventing pain in a subject by administration of an analgesic agent, even though such agent does not treat the cause of the pain. As used herein, the term “effective amount” or “therapeutically effective amount” means a dosage sufficient to treat, inhibit, or alleviate one or more symptoms of a disease state being treated or to otherwise provide a desired pharmacologic effect. The precise dosage will vary according to a variety of factors such as subject-dependent variables (e.g., age, immune system health, etc.), the disease, and the age of the subject. The term “therapeutically effective amount” means an amount of the therapeutic agent that, when incorporated into and / or onto particles described herein, produces some desired effect at a reasonable benefit / risk ratio applicable to any treatment. The effective amount may vary depending on such factors as the disease or condition being treated, the particular formulation being administered, the size of the subject, or the severity of the disease or condition. 1. Effective Amounts In some forms, the amount of homotaurine or homotaurine analog in the pharmaceutical formulation is effective to reduce one or more side effects of GLP-1 RA therapy. The amount of homotaurine or homotaurine analog in the pharmaceutical formulation is determined to be effective in reducing one or more gastrointestinal side effects commonly associated with GLP-1 receptor agonist (GLP-1 RA) therapies. For example, the amount of homotaurine or homotaurine analog in the pharmaceutical formulation is effective to reduce symptoms such as nausea, vomiting, and constipation. These side effects are often reported by patients undergoing GLP-1 RA therapy and reducing them can significantly improve patient comfort and adherence to a treatment regimen. The inclusion of homotaurine or its analogs in the pharmaceutical formulation is based on their known properties of modulating neurotransmitter activity and osmoregulation, which can help normalize gastrointestinal function disrupted by GLP-1 RA therapy. For example, one acamprosate tablet weights 533 mg and contains 333 mg acamprosate calcium; thus, acamprosate calcium is present in the tablet at about 62.5% weight percent (wt%). The homotaurine or its analog may be present at any suitable weight percent (wt%) in the pharmaceutical formulation for parenteral or enteral administration. In some forms, the homotaurine or its analog in the pharmaceutical formulation are collectively at a concentration of at least 1.0 wt%, at least 0.5 wt%, at least 0.1 wt%, in a range from about 1.0 wt% to about 99 wt%, from about 0.5 wt% to about 99 wt%, from about 0.1 to about 99 wt%, from about 1.0 wt% to about 95 wt%, from about 1.0 wt% to about 90 wt%, from about 1.0 wt% to about 85 wt%, from about 1.0 wt% to about 80 wt%, from about 1.0 wt% to about 75 wt%, from about 1.0 wt% to about 70 wt%, from about 1.0 wt% to about 65 wt%, from about 1.0 wt% to about 60 wt%, from about 1.0 wt% to about 55 wt%, from about 1.0 wt% to about 50 wt%, from about 1.0 wt% to about 45 wt%, from about 1.0 wt% to about 40 wt%, from about 1.0 wt% to about 35 wt%, from about 1.0 wt% to about 30 wt%, from about 1.0 wt% to about 25 wt%, from about 1.0 wt% to about 20 wt%, from about 1.0 wt% to about 15 wt%, from about 1.0 wt% to about 10 wt%, or from about 1.0 wt% to about 5 wt%. In some forms, the dosage of the HTL-GIDR composition administered to human subjects is calibrated based on what is known as a human equivalent dose (HED). This HED can be derived from dosages that have been found sufficient to prevent weight loss in rat models treated with liraglutide, a common GLP-1 receptor agonist. The process involves calculating the effective dose in rats that counteracts the weight loss typically induced by liraglutide and then adjusting this dose for humans based on body surface area ratios and other pharmacokinetic factors. This method can be used to determine a safe and effective dose of the HTL-GIDR composition that can be administered to the subject replicating the therapeutic benefits observed in preclinical trials without inducing adverse effects. In some forms, the amount of the HTL-GIDR composition administered to the subject is the human equivalent dosage of a dosage sufficient to prevent weight loss in rats receiving liraglutide. In some forms, the amount of the HTL-GIDR composition administered to the subject is the human equivalent dosage of a dosage sufficient to increase appetite in rats receiving liraglutide. In some forms, the amount of the HTL-GIDR composition administered to the subject is the human equivalent dosage of a dosage sufficient to reduce weight loss in rats receiving liraglutide. The dosage of HTL GIDR compositions administered to humans is typically lower than the equivalent dosage used in animal models, such as rats, due to the generally slower metabolic rate in humans. In practice, the human dosage is usually 5 to 20 times lower than the corresponding animal dosage. For example, in some forms, the amount of HTL GIDR composition administered to a human subject is the human equivalent dosage of a dose sufficient to prevent weight loss in rats receiving liraglutide. Similarly, the human equivalent dosage may correspond to a dose sufficient to increase appetite or reduce weight loss in rats receiving liraglutide. This adjustment in dosage accounts for metabolic differences between species, ensuring safe and effective administration in human subjects. The dosage of each compound for administration to humans is dependent on various factors, including the patient's age, body weight, and severity of side effects. For oral administration, the total daily oral dose of the homotaurine or its analog can range from about 100 mg to about 3000 mg. In some forms, the daily oral dose of the homotaurine or its analog can range from about 100 mg to about 2900 mg, from about 100 mg to about 2500 mg, from about 100 mg to about 2300 mg, from about 100 mg to about 2100 mg, from about 100 mg to about 2000 mg, from about 100 mg to about 1900 mg, from about 100 mg to about 1800 mg, from about 100 mg to about 1700 mg, from about 100 mg to about 1600 mg, from about 100 mg to about 1500 mg, from about 100 mg to about 1400 mg, from about 100 mg to about 1300 mg, from about 100 mg to about 1200 mg, from about 100 mg to about 1100 mg, from about 100 mg to about 1000 mg, from about 100 mg to about 900 mg, from about 100 mg to about 800 mg, from about 100 mg to about 700 mg, from about 100 mg to about 600 mg, from about 100 mg to about 500 mg, from about 100 mg to about 400 mg, from about 100 mg to about 300 mg, from about 100 mg to about 200 mg, from about 100 mg to about 180 mg, from about 100 mg to about 160 mg, or from about 100 mg to about 140 mg. Homotaurine or its analogues may be administered 1 to 3 times daily as necessary, with the maximum dose per administration being one-third of the prescribed maximum daily dose. For example, if the maximum daily dose is 300 mg, and the medication is administered three times daily, the maximum dose per administration is 100 mg. When administered via intraperitoneal (IP), intravenous (IV), or subcutaneous (SC) injection, the daily dosage of homotaurine or its analogues may range from about 20 mg to about 600 mg per day. In some forms, the amount of the HTL-GIDR composition administered to the subject is the human equivalent dosage of a dosage of the HTL-GIDR sufficient to reduce one or more GLP-1 RA therapy induced negative side effects in rats receiving liraglutide. 2 Dosage Regiments In some forms, the HTL-GIDR composition is administered to a subject receiving GLP-1 receptor agonist therapy in a dosage that has been determined based on animal model studies to counteract the appetite-suppressing effects of liraglutide, a GLP-1 receptor agonist. Data in the non-limiting Examples demonstrate that subcutaneous administration of 50 mg / kg of the exemplary HTL-GIDR, homotaurine, can effectively increase appetite in rats treated with liraglutide, indicating the potential of HTL-GIDR compositions to manage these side effects in humans as well (see Figures 5A-5C). Thus, in some forms, the HTL-GIDR composition is administered to a subject at a dosage sufficient to increase appetite in rats receiving liraglutide. It is understood that the actual dosage of the administered drug will be determined by the physician based on varying factors, including the condition or conditions being treated, the exact composition administered, the individual patient's age, weight, and response, the severity of the 33 patient's symptoms, and the chosen route of administration. Consequently, the dosage ranges provided above are intended to offer general guidelines and support the teachings presented here but are not intended to be limiting. For example, homotaurine or its analogs can be administered 1 to 3 times daily, as needed. In some forms, the maximum oral dose per administration is one-third of the maximum prescribed daily dose. For example, if the oral maximum daily dose is 3000 mg and the medication is taken 3 times a day, the maximum dose per administration is 1000 mg. Additionally, in some forms, the dosage of HTL-GIDR is selected to address and rectify liraglutide-induced alterations in feeding and drinking behaviors. For example, as demonstrated in the non-limiting examples, rats previously habituated to consume cherry juice while receiving saline injections, begin to exhibit abnormal feeding and drinking patterns under liraglutide treatment. Therefore, in some forms, the dosage of the HTL-GIDR administered to the subject is able to rescue liraglutide induced abnormal feeding and drinking behavior in rats that had been habituated to drink cherry juice while receiving saline injections. Similar adjustments can be made to the composition for administration to humans. In some forms, the adjusted dosage of HTL-GIDR restores these behaviors to normal levels, suggesting its utility in normalizing feeding habits disrupted by GLP-1 RA. In some forms, administration of the HTL-GIDR helps maintain normal dietary and hydration habits in patients undergoing treatment with liraglutide, thus improving overall adherence to treatment and quality of life. In some forms, the HTL-GIDR compositions are formulated in dosage unit form for ease of administration and uniformity of dosage. “Dosage unit form” as used herein refers to physically discrete units suited as unitary dosages for the patients to be treated; each unit containing a predetermined quantity of therapeutic agent calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. In some forms, the specification for the dosage unit forms of the invention is dictated by and directly dependent on (a) the unique characteristics of the therapeutic agent and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding such a therapeutic agent for the treatment of a selected condition in a patient. In some forms, the homotaurine and / or homotaurine analog (s) are administered at a therapeutically effective dosage sufficient to treat a condition associated with a condition in a patient. For example, the efficacy of an HTL-GIDR composition containing one or more homotaurine and / or homotaurine analog (s) can be evaluated in an animal model system that may be predictive of efficacy in treating the disease in a human or another animal. In some forms, the effective dose range for the therapeutic agent can be extrapolated from effective doses determined in animal studies for a variety of different animals. Precise amounts of the HTL-GIDR composition depend on the judgment of the practitioner and are specific to each individual. Other factors affecting the dose include the physical and clinical state of the patient, the route of administration, the intended goal of treatment and the potency, stability, and toxicity of the particular HTL-GIDR composition. The actual dosage amount of a HTL-GIDR composition of the present disclosure administered to a patient may be determined by physical and physiological factors such as type of animal treated, age, sex, body weight, severity of condition, the type of condition being treated, previous or concurrent therapeutic interventions, idiopathy of the patient and on the route of administration. These factors may be determined by a skilled artisan. The practitioner responsible for administration will typically determine the concentration of active ingredient(s) in a composition and appropriate dose(s) for the individual patient. The dosage may be adjusted by the individual physician in the event of any complication. Single or multiple doses of the agents are contemplated. Desired time intervals for delivery of multiple doses can be determined by one of ordinary skill in the art employing no more than routine experimentation. As an example, patients may be administered two doses daily at approximately 12-hour intervals. In some forms, the agent is administered once a day. The composition may be administered on a routine schedule. As used herein, a routine schedule refers to a predetermined designated period of time. The routine schedule may encompass periods of time which are identical, or which differ in length, as long as the schedule is predetermined. For instance, the routine schedule may involve administration twice a day, every day, every two days, every three days, every four days, every five days, every six days, a weekly basis, a monthly basis or any set number of days or weeks there-between. Alternatively, the predetermined routine schedule may involve administration on a twice daily basis for the first week, followed by a daily basis for several months, etc. In other forms, the invention provides that the agent(s) may be taken orally and that the timing of which is or is not dependent upon food intake. Thus, for example, the agent can be taken every morning and / or every evening, regardless of when the patient has eaten or will eat. 3. Subjects and Conditions to Be Treated In some forms, the HTL-GIDR composition is administered to a subject receiving GLP-1 RA therapy. In some forms, the subject is suffering negative side effects of GLP-1 RA therapy e.g., nausea, vomiting, constipation, or combinations thereof. Other negative side effects of GLP- 1 RA therapy include but are not limited to headaches, indigestion, dizziness, stomach pain, feeling of lightheadedness, arthralgia, and fatigue. Generally, the subject undergoing treatment is receiving GLP-1 receptor agonist (GLP-1 RA) therapy. This type of therapy primarily involves the administration of medications that act by stimulating the GLP-1 receptor, which plays a significant role in glucose regulation and appetite control. GLP-1 RAs are designed to mimic the action of the naturally occurring incretin hormone known as glucagon-like peptide-1, which is involved in promoting insulin secretion in response to meals. In some forms, the GLP-1 RA therapy encompasses the administration of any pharmaceutical agent that functions as an agonist to the GLP-1 receptor. These medications can vary widely but share the common therapeutic goal of enhancing the receptor's activity to improve glycemic control, often leading to secondary benefits such as weight loss and reduced appetite. Common examples of such medications include liraglutide, exenatide, and dulaglutide, among others. These agents are used in a variety of clinical contexts, primarily for managing type 2 diabetes and, in some cases, for weight management in individuals who are obese or overweight. For example, the GLP-1 RA therapy includes administration of albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, tirzepatide, danuglipron, orforglipron, retatrutide, efpeglenatide, ALT-801, cotadutide, mazdutide, BI 456905, BI 456906, BI 442524, PF-07081532, SAR425899, TTP273, BAT1706, MN-850, APD334, CT-996, CT-388, DA-JC4, DA-CH5, XW003, NNC9204-1706, IMB-2024, SCO-267, NLY01, MK-8521, HM15211, DMB-3115, RG7697, RG7906, RG1067, or combinations thereof. Typically, the HTL-GIDR composition is administered to a subject undergoing treatment with one or more GLP-1 receptor agonists. The HTL-GIDR composition is generally administered to the subject after the onset of one or more adverse symptoms associated with GLP-1 receptor agonist therapy. These adverse symptoms may include, but are not limited to, gastrointestinal discomfort such as nausea, vomiting, diarrhea, or abdominal pain. Additionally, subjects may experience other systemic side effects, such as dizziness, headache, or fatigue, as a result of GLP-1 receptor agonist treatment. The administration of HTL-GIDR composition is administered to alleviate or reduce the severity of one or more of these symptoms, thereby improving or increasing the subject’s tolerance to the therapy and increasing overall treatment adherence. The HTL-GIDR composition may be administered as an adjunct treatment to mitigate or reduce adverse side effects associated with the administration of one or more GLP-1 receptor agonists, thereby increasing the subject's ability to tolerate and continue receiving GLP-1 receptor agonist therapy. For example, following the administration of a GLP-1 receptor agonist, such as by injection or orally via tablet, the subject experiences symptoms such as nausea or abdominal pain. In some forms, upon the onset of such symptoms, the subject may self-administer the HTL-GIDR composition. In this form, the HTL-GIDR composition may be provided as a dissolvable tablet, which the subject dissolves in a liquid, such as water, and consumes. In some forms, the HTL-GIDR composition may be administered by a healthcare professional, for example, via intravenous injection. In the context of GLP-1 receptor agonist (GLP-1 RA) therapy, the term "high dose" refers to a dosage that achieves a therapeutic effect in a patient without exceeding the maximum recommended dose as outlined in established clinical treatment guidelines. The precise dosage required to achieve a therapeutically effective outcome varies among patients due to individual differences in drug tolerance and physiological response. For instance, while certain patients may experience restoration of beta-cell function at a dosage as low as 0.5 mg / week of semaglutide, others may necessitate an increased dose of up to 1 mg / week to achieve similar therapeutic effects. Consider a scenario in which a patient receiving 0.5 mg / week of semaglutide exhibits no significant antidiabetic response and cannot tolerate an increased dosage to 1 mg / week due to adverse gastrointestinal side effects. In such cases, co-administration of homotaurine or its analogs may mitigate these side effects, thereby enabling the patient to tolerate a higher semaglutide dosage. Consequently, this adjustment in dosage, facilitated by the use of homotaurine or its analogs, would enhance the patient's therapeutic response to semaglutide, resulting in improved management of their diabetic condition. In some forms, the HTL-GIDR composition is administered to a subject receiving dulaglutide. In some forms, dulaglutide is used at a dosage of from about 0.75 mg / week to about 1.5 mg / week. For example, the dulaglutide can be used at a dosage of about 0.75 mg / week, about 1.00 mg / week, about 1.10 mg / week, about 1.20 mg / week, about 1.30 mg / week, about 1.40 mg / week, about 1.50 mg / week, about 1.60 mg / week, up to about 1.75 mg / week. In some forms, the HTL-GIDR composition is administered to a subject receiving exenatide. In some forms, the exenatide is used at a dosage of from about 10 pg / day to about 20 pg / day. In some forms, the HTL-GIDR composition is administered to a subject receiving exenatide extended. For example, exenatide can be used at a dosage of about 12 pg / day, about 13 pg / day, about 14 pg / day, about 15 pg / day, about 16 pg / day, about 17 pg / day, about 18 pg / day, about 19 pg / day, up to about 20 pg / day. In some forms, exenatide extended is used at a dosage of about 2 mg / week. For example, exenatide extended can be used at a dosage of about 1 mg / week, about 1.5 mg / week, about 2 mg / week, about 2.5 mg / week, up to about 3 mg / week. In some forms, the HTL-GIDR composition is administered to a subject receiving liraglutide. In some forms, liraglutide is used at a dosage of about 0.6 mg / day to about 3 mg / day. For example, liraglutide can be used at a dosage of from about 0.6 mg / day to about 2.5 mg / day; from about 0.6 mg / day to about 2.3 mg / day; from about 0.6 mg / day to about 2.0 mg / day; from about 0.6 mg / day to about 1.8 mg / day; from about 0.6 mg / day to about 1.6 mg / day; from about 0.6 mg / day to about 1.4 mg / day; from about 0.6 mg / day to about 1.2 mg / day; from about 0.6 mg / day to about 1.0 mg / day; or from about 0.6 mg / day to about 0.8 mg / day. In some forms, the HTL-GIDR composition is administered to a subject receiving lixisenatide. In some forms, the lixisenatide is used at a dosage of about 10 pg / day to about 20 pg / day. For example, lixisenatide can be used at a dosage of from about 10 pg / day to about 18 pg / day, from about 10 pg / day to about 16 pg / day, or from about 10 pg / day to about 14 pg / day, or from about 10 pg / day to about 12 pg / day. In some forms, the HTL-GIDR composition is administered to a subject receiving semaglutide. In some forms, the semaglutide is used at an oral dosage of about 3 mg / day to about 14 mg / day or an injection dosage of about 0.25 to about 1 mg / week. For example, the semaglutide can be used at an oral dosage of from about 3 mg / day to about 12 mg / day, from about 3 mg / day to about 10 mg / day, from about 3 mg / day to about 8 mg / day, or from about 3 mg / day to about 6 mg / day. In some forms, the HTL-GIDR composition is administered to a subject receiving tirzepatide. In some forms, the tirzepatide is used at a dosage of about 2.5 to about 15 mg / week. For example, the tirzepatide can be used at a dosage of from about 2.5 to about 13 mg / week, from about 2.5 to about 11 mg / week, from about 2.5 to about 9 mg / week, from about 2.5 to about 7 mg / week, or from about 2.5 to about 5 mg / week. In some forms, the HTL-GIDR composition is administered to a subject receiving albiglutide. In some forms albiglutide is used at a dosage from about 30 mg / week to about 50 mg / week. For example, the albiglutide can be used at a dosage from about 30 mg / week to about 48 mg / week, from about 30 mg / week to about 46 mg / week, from about 30 mg / week to about 44 mg / week, from about 30 mg / week to about 42 mg / week, from about 30 mg / week to about 40 mg / week, from about 30 mg / week to about 38 mg / week, or from about 30 mg / week to about 36 mg / week. In some forms, the HTL-GIDR composition can be administered to a subject in need thereof either concurrently with, or in conjunction with, the administration of one or more GLP-1 receptor agonists (GLP-1 RAs). In these forms, the subject is capable of receiving and tolerating a higher dosage of the GLP-1 RA therapy than would be tolerable in the absence of the administration of the HTL-GIDR composition. For example, subjects receiving the HTL-GIDR composition in conjunction with GLP-1 RA therapy may be capable of tolerating escalated dosages of GLP-1 RA, i.e., dosages that would typically exacerbate side effects such as nausea, vomiting, and gastrointestinal discomfort, thus limiting the maximum dose tolerable by the subject. The administration of the HTL-GIDR composition effectively mitigates or reduces these adverse side effects, thereby allowing the subject to tolerate higher dosages of GLP-1 RA therapy than would otherwise be achievable. This increased tolerance is particularly advantageous for subjects requiring more aggressive or intensive treatment regimens, such as those managing type 2 diabetes or obesity, where higher dosages of GLP-1 RAs may be necessary for optimal therapeutic outcomes. The described optimal therapeutic outcomes include achieving the best clinical results from GLP-1 RA therapy, such as improved blood glucose control and increased weight loss, while minimizing adverse effects like nausea and vomiting, thereby maximizing the treatment's benefits for the patient. Thus, by allowing for the administration of higher dosages, the HTL-GIDR composition enhances the therapeutic efficacy of GLP-1 RA therapy, resulting in improved control of blood glucose levels, greater weight loss, and overall improved treatment outcomes for the subject. In some forms, the HTL-GIDR composition increases tolerance by improving gastrointestinal physiology, such as reducing inflammation or altering neural signaling pathways that influence gastrointestinal discomfort. This aspect of the HTL-GIDR composition makes it a valuable adjunct in the management of diabetes and related metabolic disorders where GLP-1 RA therapies are indicated. In some forms, the subject is receiving the GLP-1 RA therapy as a treatment for diabetes, incipient diabetes, or the risk of diabetes. A well-established application of GLP-1 RA therapy is for increasing insulin secretion in a glucose-dependent manner, reducing glucagon secretion, and delaying gastric emptying, thereby improving glycemic control and reducing the risk of hypoglycemia in patients with diabetes. In some forms, the subject has incipient diabetes. In subjects with prediabetes, the goal of administering GLP-1 RA therapy is to delay or prevent the onset of type 2 diabetes by improving insulin sensitivity and pancreatic P-cell function, thereby managing high blood sugar levels before they escalate to diabetes. In some forms, the subject is at risk of diabetes. For individuals at high risk of developing diabetes, GLP-1 RA therapy serves as a preventive measure. By improving metabolic functions early, GLP-1 RA therapy aims to avert the progression to type 2 diabetes, thereby addressing one of the key modifiable risk factors for this condition. In other forms, the subject is receiving GLP-1 receptor agonist (GLP-1 RA) therapy for treatment beyond traditional uses, such as the treatment of type 2 diabetes, to include a broader spectrum of diseases characterized by metabolic dysfunction, cellular degeneration, and abnormal cell growth. These include but are not limited to cancer, neurodegeneration, excess body weight, and risk of neurodegeneration. In some forms, the subject can be receiving GLP-1 RA therapy for the treatment of cancer. Utilizing GLP-1 RA therapy in cancer treatment involves leveraging its potential antiproliferative effects on certain tumor cells. Research suggests that GLP-1 RAs may influence pathways that inhibit cancer cell growth and improve metabolic profiles, which can be advantageous in cancer therapy. In some forms, the subject can be receiving GLP-1 RA therapy for the treatment of cardiovascular disease. Utilizing GLP-1 RA therapy in cardiovascular disease treatment involves leveraging its potential protective effects on the heart and blood vessels. Research suggests that GLP-1 RAs may influence pathways that improve vascular function and reduce inflammation, which can be advantageous in cardiovascular therapy. In some forms, the subject can be receiving GLP-1 RA therapy for the treatment of aging. Utilizing GLP-1 RA therapy in aging treatment involves leveraging its potential effects on cellular health and longevity. Research suggests that GLP-1 RAs may influence pathways that improve metabolic profiles, reduce oxidative stress and reactive gliosis and improve autophagy, which can be advantageous in promoting healthy aging. In some forms, the subject can be receiving GLP-1 RA therapy for the treatment of a neurodegenerative disease. Emerging studies suggest that GLP-1 RAs may confer neuroprotective effects, potentially beneficial in treating or delaying the progression of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. The mechanisms might involve anti-inflammatory effects, improvement in brain insulin signaling, and reduction of amyloid plaques. In some forms, the subject is at risk of developing a neurodegenerative disease. Given the potential neuroprotective properties of GLP-1 RAs, their use in individuals at risk of neurodegenerative diseases could help in reducing the progression or onset of such conditions. In some forms, the subject can be receiving GLP-1 RA therapy for the treatment of excess body weight. GLP-1 RAs are used to manage obesity as they help reduce appetite and increase satiety through delayed gastric emptying and enhanced brain signaling that promotes a feeling of fullness after meals. In these forms, the use of GLP-1 RA therapy is adapted to the specific needs and conditions of the patient. In some forms, the subject maintains a higher body weight than the subject would maintain in the absence of the administration of the HTL-GIDR. The administration of the HTL-GIDR composition results in the subject maintaining a higher body weight than would be observed without this treatment. This effect can be particularly significant in scenarios where the subject is undergoing treatments that typically reduce appetite or disrupt normal feeding patterns, such as certain pharmaceutical regimens or medical conditions. The HTL-GIDR composition can act to counteract these weight-reducing effects through mechanisms that may include enhancing appetite, modulating metabolic rates, or improving nutrient absorption. By stabilizing the gastrointestinal environment, HTL-GIDR may also help alleviate symptoms like nausea or vomiting, which can further contribute to weight loss in untreated individuals. As a result, patients can maintain a healthier body weight, which is crucial for overall vitality, especially in those suffering from chronic illnesses or undergoing intensive medical treatments where weight loss can be a significant concern. 4. Routes of Administration The disclosed HTL-GIDR compositions containing one or more homotaurine and / or homotaurine analog (s) in an amount sufficient to reduce one or more side effects in a subject receiving GLP-1 receptor agonist therapy are typically administered according to methods known for administering small molecule drugs to subjects. In some forms, the HTL-GIDR composition containing one or more homotaurine and / or homotaurine analog (s) are administered parenterally. The phrases “parenteral administration” and “administered parenterally” are art-recognized terms, and include modes of administration other than enteral and topical administration, such as injections, and include without limitation intravenous, intramuscular, intrapleural, intravascular, intrapericardial, intraarterial, intrathecal, intratracheal, intranasal intracapsular, intraorbital, intracardiac, intradennal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrastemal injection and infusion. The disclosed HTL-GIDR composition containing one or more homotaurine and / or homotaurine analog (s) can be administered parenterally, for example, by subdural, intravenous, intrathecal, intraventricular, intraarterial, intra-amniotic, intraperitoneal, or subcutaneous routes. For example, Cammalleri et aL, Nutrients, 12(4):1189 (2020) describes intraocular and intravitreal injection of a combination of homotaurine and one or more other agents such as vitamin B for the treatment of hypertensive glaucoma. In another example, Paakkari, et al.. Medical Biology, 60(6):316-322 (1982) describes intracerebroventricular and intravenous administration of taurine and homotaurine. In another example, Zornoza et al., Biopharmaceutics &Drug Disposition, 23(7):283-291 (2002) describes the intravenous administration of acamprosate calcium. The disclosed HTL-GIDR composition containing one or more homotaurine and / or homotaurine analog (s) can be administered via oral, intraperitoneal, intravenous, or subcutaneous administration. In some forms, the HTL-GIDR composition is administered via oral administration. In other forms, the HTL-GIDR composition is administered via injection such as by subcutaneous injection, intravenous injection, or intraperitoneal injection. It is to be understood that the disclosed methods are not limited to specific synthetic methods, specific analytical techniques, or to particular reagents unless otherwise specified, and, as such, can vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. The disclosed methods can be further understood through the following numbered paragraphs. The invention provides, inter alia, the subject matter of these numbered paragraphs. Paragraph 1. A method comprising administering to a subject receiving glucagon-like peptide 1 (GLP 1) receptor agonist (RA) therapy an amount of homotaurine-like gastrointestinal distress-relieving (HTL GIDR) composition effective to reduce one or more gastrointestinal side effects of GLP 1 RA therapy. Paragraph 2. The method of paragraph 1, wherein the gastrointestinal side effects are selected from the group consisting of nausea, vomiting, loss of appetite, weight loss, weight gain, and constipation. Paragraph 3. The method of paragraph 1, wherein the HTL GIDR comprises homotaurine, acamprosate calcium, valiltramiprosate, 3 sulfopropanoic acid or a combination thereof. Paragraph 4. The method of any one of paragraphs 1-3, wherein the HTL GIDR does not comprise taurine. Paragraph 5. The method of any one of paragraphs 1-4, wherein the amount of the HTL GIDR is the human equivalent dosage of a dosage sufficient to increase appetite in rats receiving liraglutide. Paragraph 6. The method of any one of paragraphs 1-5, wherein the amount of the HTL GIDR is the human equivalent dosage of a dosage sufficient to reduce weight loss in rats receiving liraglutide. Paragraph 7. The method of any one of paragraphs 1-6, wherein the amount of the HTL GIDR is the human equivalent dosage of a dosage sufficient to prevent weight loss in rats receiving liraglutide. Paragraph 8. The method of any one of paragraphs 1-7, wherein the amount of the HTL GIDR is the human equivalent dosage of a dosage of the HTL GIDR sufficient to reduce one or more GLP 1 RA therapy induced negative side effects in rats receiving liraglutide. Paragraph 9. The method of paragraph 8, wherein the one or more GLP 1 RA therapy induced negative side effects are nausea, vomiting, constipation, or combinations thereof. Paragraph 10. The method of any one of paragraphs 2-9, wherein the dosage sufficient to increase appetite in rats receiving liraglutide is able to rescue liraglutide induced abnormal feeding and drinking behavior in rats that had been habituated to drink cherry juice while receiving saline injections. Paragraph 11. The method of any one of paragraphs 1-10, wherein the HTL GIDR is in a unit dose formulation. Paragraph 12. The method of any one of paragraphs 1-11, wherein the GLP 1 RA therapy comprises administration of any medication whose therapeutic effect is to agonize the GLP1 receptor. Paragraph 13. The method of any one of paragraphs 1-12, wherein the GLP 1 RA therapy comprises administration of albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, tirzepatide, danuglipron, orforglipron, retatrutide, efpeglenatide, ALT 801, cotadutide, mazdutide, BI 456905, BI 456906, BI 442524, PF 07081532, SAR425899, TTP273, BAT1706, MN 850, APD334, CT 996, CT 388, DA JC4, DA CH5, XW003, NNC9204 1706, IMB 2024, SCO 267, NLY01, MK 8521, HM15211, DMB 3115, RG7697, RG7906, RG1067, or combinations thereof. Paragraph 14. The method of paragraph 13, wherein dulaglutide is used at a dosage of 0.75 1.5 mg / week, exenatide is used at a dosage of 10 20 pg / day, exenatide extended is used at a dosage of 2 mg / week, liraglutide is used at a dosage of 0.6 3 mg / day, lixisenatide is used at a dosage of 10 20 pg / day, albiglutide is used a dosage of 30-50 mg / week, semaglutide is used at an oral dosage of 3 14 mg / day or an injection dosage of 0.25 1 mg / week, and / or tirzepatide is used at a dosage of 2.5 15 mg / week. Paragraph 15. The method of any one of paragraphs 1-14, wherein the subject is receiving and tolerating a higher dosage of the GLP 1 RA therapy than the subject could tolerate in the absence of the administration of the HTL GIDR. Paragraph 16. The method of paragraph 15, wherein the higher dosage of the GLP 1 RA therapy provides greater therapeutic effect to the subject. Paragraph 17. The method of any one of paragraphs 1-16, wherein the subject is receiving the GLP 1 RA therapy as a treatment for cancer, diabetes, neurodegeneration, excess body weight, incipient diabetes, risk of diabetes, cardiovascular disease, or risk of neurodegen erati on. Paragraph 18. The method of any one of paragraphs 1-17, wherein the subject maintains a higher body weight than the subject would maintain in the absence of the administration of the HTL GIDR. Paragraph 19. Use of a homotaurine-like gastrointestinal distress-relieving (HTL GIDR) composition for reducing one or more gastrointestinal side effects in a subject receiving glucagon-like peptide 1 (GLP-1) receptor agonist (RA) therapy. Paragraph 20. Use according to paragraph 19, wherein the gastrointestinal side effects are selected from the group consisting of nausea, vomiting, loss of appetite, weight loss, weight gain, and constipation. Paragraph 21. Use according to paragraph 19, wherein the HTL GIDR composition comprises homotaurine, acamprosate calcium, valiltramiprosate, 3-sulfopropanoic acid, or a combination thereof. Paragraph 22. Use according to any one of paragraphs 19-21, wherein the HTL GIDR composition does not comprise taurine. Paragraph 23. Use according to any one of paragraphs 19-22, wherein the amount of the HTL GIDR composition is the human equivalent dosage of a dosage sufficient to increase appetite in rats receiving liraglutide. Paragraph 24. Use according to any one of paragraphs 19-23, wherein the amount of the HTL GIDR composition is the human equivalent dosage of a dosage sufficient to reduce weight loss in rats receiving liraglutide. Paragraph 25. Use according to any one of paragraphs 19-24, wherein the amount of the HTL GIDR composition is the human equivalent dosage of a dosage sufficient to prevent weight loss in rats receiving liraglutide. Paragraph 26. Use according to any one of paragraphs 19-25, wherein the amount of the HTL GIDR composition is the human equivalent dosage sufficient to reduce one or more GLP-1 RA therapy-induced negative side effects in rats receiving liraglutide. Paragraph 27. Use according to paragraph 26, wherein the one or more GLP-1 RA therapy-induced negative side effects are selected from nausea, vomiting, constipation, or combinations thereof. Paragraph 28. Use according to any one of paragraphs 20-27, wherein the dosage sufficient to increase appetite in rats receiving liraglutide is able to rescue liraglutide-induced abnormal feeding and drinking behavior in rats habituated to drink cherry juice while receiving saline injections. Paragraph 29. Use according to any one of paragraphs 19-28, wherein the HTL GIDR composition is in a unit dose formulation. Paragraph 30. Use according to any one of paragraphs 19-29, wherein the GLP-1 RA therapy comprises administration of any medication whose therapeutic effect is to agonize the GLP-1 receptor. Paragraph 31. Use according to any one of paragraphs 19-30, wherein the GLP-1 RA therapy comprises administration of albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, tirzepatide, danuglipron, orforglipron, retatrutide, efpeglenatide, ALT-801, cotadutide, mazdutide, BI 456905, BI 456906, BI 442524, PF-07081532, SAR425899, TTP273, BAT1706, MN-850, APD334, CT-996, CT-388, DA-JC4, DA-CH5, XW003, NNC9204-1706, IMB-2024, SCO-267, NLY01, MK-8521, HM15211, DMB-3115, RG7697, RG7906, RG1067, or combinations thereof. Paragraph 32. Use according to paragraph 31, wherein dulaglutide is used at a dosage of 0.75-1.5 mg / week, exenatide is used at a dosage of 10-20 pg / day, exenatide extended is used at a dosage of 2 mg / week, liraglutide is used at a dosage of 0.6-3 mg / day, lixisenatide is used at a dosage of 10-20 pg / day, albiglutide is used at a dosage of 30-50 mg / week, semaglutide is used at an oral dosage of 3-14 mg / day or an injection dosage of 0.25-1 mg / week, and / or tirzepatide is used at a dosage of 2.5-15 mg / week. Paragraph 33. Use according to any one of paragraphs 19-32, wherein the subject is receiving and tolerating a higher dosage of the GLP-1 RA therapy than the subject could tolerate in the absence of the administration of the HTL GIDR composition. Paragraph 34. Use according to paragraph 33, wherein the higher dosage of the GLP-1 RA therapy provides a greater therapeutic effect to the subject. Paragraph 35. Use according to any one of paragraphs 19-34, wherein the subject is receiving the GLP-1 RA therapy as a treatment for cancer, diabetes, neurodegeneration, excess body weight, incipient diabetes, risk of diabetes, cardiovascular disease, or risk of neurodegen erati on. Paragraph 36. Use according to any one of paragraphs 19-35, wherein the subject maintains a higher body weight than the subject would maintain in the absence of the administration of the HTL GIDR composition. Examples Materials and Methods Animals Experiments were approved by the Estonian Project Authorization Committee for Animal Experiments (nr. 230 and nr. 1.2-13 / 79), and performed in accordance with the ARRIVE guidelines and European Communities Directive of September 2010 (2010 / 63 / EU). Generation and phenotyping of Wfsl mutant rats has been previously described (Wfsl coding exon 5 knockout, Wfsl KO) (41). Breeding and genotyping were conducted at the Laboratory Animal Centre at the University of Tartu, Estonia. Experimental setups included following rats and strains: (i) 5-6-month-old male homozygous Wfsl KO (Wfsl KO, KO) with genetic background Sprague Dawley (CD®IGS, Charles River Laboratory); (ii) 5-6-month-old male homozygous Wild-type (WT) littermates with genetic background Sprague Dawley (CD®IGS, Charles River Laboratory); (iii) 2 month-old young male outbred Wistar Hannover rats from Taconic Farms. The animals were housed in cages (2-3 per cage) under a 12-hour light / dark cycle (lights on at 7 a.m.) and were randomly assigned to study groups at the start of the treatment. Animals had ad-libitum access to food (Sniff #V1534) and reverse osmosis-purified water (or depending on the treatment GABA / Taurine solution, see below) except during active experiments. Drugs and Administration Animals were weighed at the beginning of the week (or daily as noted below) to adjust subsequent medication injection volumes according to their weight. (i) GABA (Sigma Aldrich A2129) and Taurine (Sigma Aldrich T8601) were prepared (dissolved) freshly every other day in reverse osmosis-purified water (concentration 12.5 mg / L). (ii) Saline (0.9% NaCl solution) was administered by daily s.c. injections (injection volume = 1 ml / kg). (iii) Liraglutide (Victoza®, Novo Nordisk Medical, Denmark) was prepared fresh in saline (0.4 mg / ml) and administered by daily s.c. injection (injection volume = 1 ml / kg). (iv) Homotaurine (Sigma Aldrich A76109) was freshly dissolved in saline (50 mg / ml) and administered daily by s.c. injection (injection volume = 1 ml / kg) immediately after Liraglutide administration. (v) Aura Cherry juice (AS A. Le Coq, Estonia). Carbohydrate content: 12.6 %. Prior to Liraglutide injection, animals underwent a week-long habituation period during which they were accustomed to drinking the corresponding amino acids and daily saline injections. Experimental Setup for GABA and Taurine Treatment Study WT and Wfsl KO male rats were 5 months old at the start of the treatment and randomly divided into study groups presented in Table 1. The liraglutide-treated animals received 0.4 mg / kg liraglutide, and the control groups received saline. GABA and taurine were administered orally via drinking water at expected dose Ig / kg / day. Drinking was monitored over 7 days and data were presented as a mean drink intake per animal per cage. Figures 1A-1G and 2A-2D summarize the daily drinking consumptions of each treatment groups and no significant differences in drinking was observed between genotypes. Table 1: Treatment Groups and their Composition (see Figures 1A-1G and 2A-2D) Treatment Drink option &genotype Saline water (n=7, 3 WT and 4 Wfsl KO cages, 2-3 animals per cage) GABA (n=9, 3 WT and 6 Wfsl KO cages, 2-3 animals per cage) Taurine (n=6, 3 WT and 3 Wfsl KO cages, 2-3 animals per cage) Liraglutide water (n=7, 3 WT and 4 Wfsl KO cages, 2-3 animals per cage) GABA (n=7, 3 WT and 4 Wfsl KO cages, 2-3 animals per cage) Taurine (n=8, 3 WT and 5 Wfsl KO cages, 2-3 animals per cage) Experimental setup number 1 for taurine and homotaurine treatment study against liraglutide induced nausea, using cherry juice as a flavor - CD®IGS, Charles River Laboratory background Wfsl KO male rats were 6 months old at the start of the treatment and randomly divided into study groups presented in Table 2. The liraglutide-treated animals received 0.4 mg / kg liraglutide, and the control groups received a 0.9% NaCl solution (Saline). Homotaurine was administered daily by subcutaneous injection (50 mg / kg) immediately after liraglutide administration. GABA and taurine were administered orally via 1 / 5 diluted cherry juice at expected dose Ig / kg / day. Control animals where drinking 1 / 5 diluted cherry juice. Drink and diet intake were monitored over 3 days and data are presented as a mean cage drinking or diet consumption per animal. Table 2: Summarized Treatment Groups and Their Composition (see Figures 3A-3D, 4A-4D, and 5A-5C) Treatment Drink option Saline Wfsl KO cherry (n=3) Wfsl KO GABA / cherry (n=3) Wfsl KO Taurine / cherry (n=3) Liraglutide Wfsl KO cherry (n=6) Wfsl KO GABA / cherry (n=6) Wfsl KO Taurine / cherry (n=6) Liraglutide + Homotaurine Wfsl KO cherry (n=3) Wfsl KO GABA / cherry (n=3) Wfsl KO Taurine / cherry (n=3) Experimental setup number 2 for homotaurine treatment study against liraglutide induced nausea, using cherry juice as a flavor - Wistar Hannover (Taconic Farms) background 5 Wistar Hannover rats (n=6 per group) were randomly assigned into two study groups: one group receiving liraglutide alone and the other receiving a combination of liraglutide and homotaurine (Table 3). Prior to treatment, the rats underwent a 3-day habituation period during which they were acclimated to drinking a 1 / 5 dilution of cherry juice. Throughout this habituation phase, drinking behavior, food intake, and body weight were closely monitored. 10 Following the habituation period, one group of rats was administered 0.4 mg / kg / day of liraglutide via subcutaneous injection, while the other group received the same daily dose of liraglutide combined with 50 mg / kg of homotaurine, also via subcutaneous injection. Over the subsequent 3 days, body weight, stool output, fluid intake, and food consumption were systematically recorded. Data are presented as the mean consumption of drinking solution or diet 15 per animal, calculated per cage. Table 3: Summarized Treatment Groups and Their Composition (see Figures 6A-6F, 7A-7I and 8A and 8B) Liraglutide Wistar Hannover (n=6 per group) Liraglutide + Homotaurine Wistar Hannover (n=6 per group) Statistics and Data Presentation Liquid and diet consumption of each experimental group was closely monitored: consumed liquid (g) = bottle weight day before (g) - bottle weight after (g). Consumed diet (g) = diet weight day before (g) - diet weight after (g). Experimental unit in this study is diet / liquid consumption per animal. The amount of the stools (pc) and total stool weight (g) - stools found from the cage after each 24h of period where counted and weighted. Statistical analyses and data visualization were performed using the GraphPad Prism (v 10.2.3) software package for Windows. The data in Figures 1A-1G, 2A-2D, 3A-3D, 4A-4D, 5A-5C, 6A-6F, and 8A and 8B were compared using one way or two-way ANOVA followed by Bonferroni’s multiple comparisons tests. The data in Figures 7A-7I were compared using a two-tailed parametric t-test. Results Liraglutide treatment drastically decreases gamma-aminobutyric acid drink consumption in Wfsl KO and WT rats Determining gastrointestinal distress and its severity in mice and rats is generally challenging. Laboratory rodents do not exhibit an emetic response (vomiting) because their brainstem lacks the neuronal components typically responsible for emetic stimulation, such as vagal afferent stimulation (30). This absence complicates the discovery and development of antinausea and anti-vomiting drugs using rodent models, as researchers may overlook some serious side effects. However, alternative indicators such as changes in eating and drinking patterns, hormonal fluctuations (e.g., oxytocin levels), locomotor activity, and specific facial expressions (such as changes in eye opening and yawning) have been linked to gastrointestinal discomfort (31-33). These metrics allow for the assessment of sickness behavior and nausea in rodents, despite the absence of "traditional" behaviors typically associated with gastrointestinal disturbances. Using an exemplary rare disease called Wolfram Syndrome (WS) (34-37) using the WS rat model of the present study, it was observed that that GLP-1 receptor agonist liraglutide delays the progression of WS associated diabetes and neurodegeneration. After discovering deficiencies of gamma-aminobutyric acid (GABA) metabolism and potential loss of GABA-ergic pathways in Wfsl-defi ci ent rat Langerhans islets and in the brain, a series of experiments were conducted. The aim of the study was to determine the WS disease modifying effects of GABA, taurine and homotaurine co-treatment with liraglutide, with emphasis of diabetic phenotype and neurodegen erati on. First, wild type (WT) and Wolframin 1-deficient (Wfsl KO) rats were treated with daily liraglutide (an GLP1-RA) and saline injections while GABA was administered via drinking water (Figures 1A-1G, Table 1). It was found that after the first liraglutide injection the daily GABA drinking was drastically reduced in both genotypes (independent from the 7-day habituation period to drink GABA solution alone or not) - a strong indication of gastrointestinal distress (Figures 1A-1G). This likely occurred because the rats found the new taste of drinking water to cause the severe nausea actually caused by the liraglutide injection - they put the nausea in context with the new taste. Homotaurine treatment reduces liraglutide induced gastrointestinal side effects. As GABA cannot cross the blood brain barrier, an experiment was conducted in which taurine was administered in combination with liraglutide, to determine whether this coadministration is able to support GABA-ergic pathways in the brain and retina in the WS rat model. Firstly, Wfsl KO and WT control rats was habituated to drink taurine for 1 week and were given daily liraglutide injections (Figure 1A-1G, Table 1). A drastic decrease in daily drinking was expected. However, one day after the first liraglutide dose, it was observed that taurine drinking in liraglutide-treated Wfsl KO and WT rats was comparable to taurine drinking in saline-treated rats (Figures 1A-1G). This drinking behavior did not change during the first 7 days of treatment period. Water intake for liraglutide and saline treated rats was monitored (Figure 1 A). Noted that 24h time point water intake data is not shown from these animals. It is possible that either (i) rats cannot taste the taurine, (ii) taurine reduced GLP-1 receptor agonist induced gastrointestinal side effects, or (iii) taurine improved other emotional benefits as many studies have found that taurine can reduced stress, anxiety, and depression in laboratory animals (38). To determine whether rats can taste the taurine, a drinking preference test was conducted. Until this point, rats were drinking taurine for 4 weeks and treated with liraglutide for 3 weeks. During the next 72 hours all taurine drinking and liraglutide treated rats were allowed to choose between the water or taurine solution (Figures 2A-2D). Unexpectedly, it was found that all rats chose the taurine drink as the first option, drinking approximately 5-6 times more taurine than water, and this finding was independent of the genotype and treatment (Figures 2A-2D). This indicates that rats were able to taste taurine and that the taurine either reduced the gastrointestinal distress (e.g., nausea according to (ii)) or that taurine improved other emotional benefits like stress and anxiety according to (iii). To determine whether taurine supplementation was able to mitigate the strong nausea induced by the GLP-1 RA agonist liraglutide injection, an experiment using cherry juice as a new tastant was conducted. Cherry juice was chosen because it has been used to produce conditioned taste avoidance in GLP-1 RA treated rodent models (40). Wfsl KO rats were divided into three groups and habituated (24 h) to drink 1 / 5 diluted cherry juice containing: 1) 12.5g / l taurine; 2) 12.5g / l GABA; and 3) plain cherry juice. Following habituation, animals were treated with daily liraglutide and saline injections for the next 72 hours and their drinking and diet consumption was monitored. One to two cages (with 3 animals per cage) of animals were assigned to each treatment group (Table 2). After the first liraglutide injection, it was observed that eating (Figure 3 A) and drinking (Figure 3B) were drastically reduced and remained at this level during the 72 hours experimental period. Observed behavior did not depend on drinking content (GABA-cherry, taurine-cherry or cherry) (Figures 3C and 3D) indicating that the flavor of cherry juice gives strong association with nausea and rats stop drinking irrespective of whether the solution contains taurine or not. These findings indicate that taurine pretreatment and continued supplementation does not alleviate any symptoms associated with drinking and food consumption, indicating that taurine supplementation alone is not enough to reduce liraglutide (GLP1RA) induced gastrointestinal side effects (ii) if the nausea is induced by a strong flavor such as cherry juice. Therefore, taurine in drinking water can improve other emotional parameters more (iii) than it reduces nausea. The diminished anti-nausea effect of taurine in the cherry juice test can be attributed to its poor bioavailability and the extensive metabolic degradation that occurs after oral administration. Taurine is poorly absorbed in the gastrointestinal tract, which makes it challenging to use effectively in clinical practice. This is accompanied by an unfavorable ratio between administered doses and the concentrations obtained in the blood (or central nervous system) (41). These results contradict the findings from the first experiment (Figures 1A-1G). To address these drawbacks, homotaurine was tested. This compound is structurally similar to taurine but is a more potent and stable agonist of both GABA A and B receptors compared to taurine. Animals were already habituated to receiving saline injections and to drinking diluted taurine-cherry, GABA-cherry or cherry juice for 3 days. Animals were treated daily with homotaurine + liraglutide. Diet and drink intake were monitored for the next 72 hours. One cage (3 animals per cage) of animals were assigned to each treatment group (Table 2). Food and drink intake dramatically decreased following the first liraglutide injection (individual groups are shown in Figures 3 A and 3B). Surprisingly, regardless of what the animals were drinking, homotaurine treated animal both food and drink intake considerably increased in Figure 3C and 51 3D, approaching normal levels at the 72-hour time point. This result suggests that homotaurine treatment can mitigate the abnormal feeding and drinking behavior induced by liraglutide, even in the context of nausea triggered by strongly flavored cherry juice, GABA-cherry, or taurine-cherry juice solutions. During the 72 hours period the food and diet intake was decreased for all liraglutide treated rats and it was not changed in saline treated rats independent of the flavor of which animals were drinking. However, the food and drink intake were significantly increased for homotaurine + liraglutide treated rats receiving ether cherry, taurine-cherry or GABA-cherry drink solution. Therefore, to better illustrate the preliminary results treatment groups have been summarized independently of the drink (Figures 4A-4D). The ability of homotaurine to restore normal feeding and drinking behavior is supported by analysis of animal body weight (Figures 5A-5C). Regardless of the drink solution, animals receiving liraglutide exhibit continuous body weight loss over 72 hours (Figures 5A-5C). In contrast, animals treated with homotaurine + liraglutide show a decline in body weight only after the first 24 hours of treatment (Figures 5A and 5B). From the second day onward, the body weight of homotaurine + liraglutide-treated animals remains stable (Figures 5 A and 5C). In previous experiments, Sprague Dawley rats, a genetic strain known for unique feeding and drinking behaviors that may significantly differ from other rat lines, were used. Consequently, in the subsequent series of experiments, young, 2-month-old male outbred Wistar Hannover rats from Taconic Farms were used. Initially, the rats were habituated over three days to drink 1 / 5 diluted cherry juice. This was followed by the administration of 0.4 mg / kg liraglutide, either alone or combined with homotaurine (50 mg / kg), for the next three days. The consumption of the cherry juice mixture, as well as food intake and fecal output were monitored (Figures 6A-6F and 7A-7I). Similar to previous observations, it was noted that 24 hours after liraglutide administration, both drinking and food consumption drastically reduced (Figures 6A and 6F), suggesting that the new drink solution may induce a nausea-like condition in Wistar rats (Figure 6A). However, this phenotype appears to be significantly milder in rats also administered homotaurine. Interestingly, in the group receiving both liraglutide and homotaurine, fluid intake normalized within 48 hours (Figure 6B) compared to the amount of drinking solution consumed before treatment (on day 3 during the habituation period). After 72 hours, rats treated with homotaurine consumed more than before treatment, whereas fluid intake in the liraglutide group remained significantly lower compared to the pre-treatment baseline (Figures 6C). This indicates that homotaurine may suppress the context of nausea induced by liraglutide in Wistar rats, similar to results previously seen in rats with a Sprague Dawley genetic background. Unlike previous experiments, homotaurine administration for animals treated with liraglutide did not significantly improve food intake relative to pre-treatment levels (Figures 6D-6F), nor did it notably increase the total fecal stool numbers (frequency) (Figures 7D-7F). This suggests that homotaurine does not fully reduce the liraglutide-induced reduction in appetite of Wistar rats, resulting the loss of appetite and a significant decrease in body weight compared to the pre-treatment state (Figures 8A and 8B). However, it was observed that rats treated with the combination of liraglutide and homotaurine produced softer stools, leading to an increased fecal mass and average pellet weight compared to the liraglutide group alone (Figures 7A-7C, Figure 7G-7I). This indicates that, in addition to alleviating nausea, homotaurine administration may prevent liraglutide-induced constipation. In summary, homotaurine was found to be more effective than taurine in reducing nausea induced by GLP-1 agonists. This was demonstrated in experimental setups involving animals that consumed cherry juice alone, or cherry juice mixed with either GABA or taurine. Following the administration of liraglutide, all animal groups ceased eating and drinking, regardless of taurine access. However, in a subsequent test series, when animals consumed cherry juice, cherry juice mixed with taurine, or cherry juice mixed with GABA and were administered liraglutide along with homotaurine, they resumed eating and drinking in all conditions. This indicates a significant effect of homotaurine in modifying the eating and drinking behaviors post-liraglutide administration. It was noted that taurine, even at a high dosage of Ig / kg / day, did not exhibit a comparable effect. Thus, homotaurine and its analog acamprosate demonstrate a robust antinausea effect, unlike taurine which shows a relatively weak effect. Discussion and Conclusions Various incretin analogues are known to cause serious gastrointestinal side effects, with nausea and vomiting being the most common. In experimental animals, this is reflected by a drastic reduction in food and especially drink intake when the animals are offered a new-tasting drink following the administration of incretins. This leads to a strong association between the new taste and the nausea induced by incretins, causing the animals to mistakenly believe that the new-tasting drink is the source of their nausea, rather than the incretin administration itself. Previous experiments showed that the administration of the incretin analogue liraglutide resulted in a drastic reduction in the consumption of gamma-aminobutyric acid (GABA) drinking water in rats. In a new study, the co-administration of taurine with liraglutide was investigated to determine if it would enhance liraglutide's neuroprotective effects in rats with Wolfram syndrome. At the beginning of the experiment, both the Wolfram syndrome rats and their littermate controls continued to drink the taurine solution, which was an unexpected result and contradicted previous findings suggesting that: (i) taurine might alleviate the nausea induced by GLP1 receptor agonists (incretins and other small molecules), (ii) the taste of taurine might not be strong enough to create a strong association between the new taste and nausea; and (iii) taurine might provide other emotional benefits to the experimental animals, such as reducing stress and anxiety, resulting in continued consumption of the taurine drink regardless of liraglutide or saline administration. To further explore these observations, rats were habituated to drink cherry juice, cherry juice with GABA (12.5g / L), or cherry juice with taurine (12.5g / L). After 24 hours of habituation, the rats were injected with liraglutide or saline, and their drinking, eating, and body weight were monitored over 72 hours. It was found that liraglutide administration significantly decreased the consumption of all types of cherry juice, along with reduced food intake and body weight. In subsequent research, homotaurine was used due to its stronger ability to agonize GABA receptors and better bioavailability. Rats were habituated to drink cherry juice, GABA cherry juice, and taurine cherry juice. They were then administered homotaurine (50 mg / kg) and liraglutide (0.4 mg / kg), and their food and drink intake and body weight were monitored over 72 hours. Initially, liraglutide reduced body weight and food and drink intake during the first 24-hour period. However, both drink and diet intake rapidly increased in the following 48 hours, also halting the weight loss. Seventy-two hours after daily liraglutide injections, consumption of all cherry juice mixtures and food intake returned close to pre-treatment levels. This suggests that, unlike taurine, homotaurine significantly and rapidly reduces liraglutide-induced nausea in rats, regardless of whether the nausea context is induced by a strong taste such as cherry juice, GABA cherry juice, or taurine cherry juice solution. Previous experiments were conducted using middle-aged Wfsl KO and WT littermate controls with a Sprague Dawley genetic background (CD® IGS, Charles River Laboratory). Given that different rat strains may exhibit varying eating and drinking behaviors, subsequent experiments were performed using young male Wistar Hannover GALAS rats. Consistent with previous findings, liraglutide suppressed both food and cherry juice intake. However, cotreatment with liraglutide and homotaurine improved fluid intake, fecal mass, and median stool weight. These results indicate that, regardless of the rat strain used, homotaurine alleviates liraglutide-induced gastrointestinal side effects such as nausea, vomiting, and constipation. The data suggest that homotaurine treatment can mitigate liraglutide-induced abnormal feeding and drinking behaviors, even when the nausea context is created by the strong flavors of cherry juice, GABA-cherry, or taurine-cherry juice solutions. These findings strongly indicate that homotaurine and its analogues, such as acamprosate calcium and ALZ-801, can be effective in treating glucagon-like peptide 1 receptor agonists (GLP-1 RA) induced gastrointestinal side effects, including nausea, vomiting, and constipation. This is particularly relevant for subjects receiving GLP-1 RA therapy for conditions such as cancer, diabetes, neurodegeneration, excess body weight, incipient diabetes, risk of diabetes, or risk of neurodegeneration. Additionally, the use of homotaurine and its analogues may enhance tolerance to GLP-1 RA doses at the beginning and during treatment, facilitate an increase in medication doses to therapeutic levels, and, if necessary, improve eating behavior in non-obese patients undergoing GLP-1 RA treatment when the treatment goal is not weight loss. References 1. WHO. Diabetes [Internet], 2022. Available from: https: / / www.who.int / news-room / fact-sheets / detail / diab ete s 2. WHO. Obesity and overweight [Internet], Available from: https: / / www.who.int / en / news-room / fact-sheets / detail / obesity-and-overweight 3. Gardner DG SD eds. Greenspan’s Basic &Clinical Endocrinology, 9e. 2011. 4. Diabetes facts and figures. 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Hom CC, Kimball BA, Wang H, Kaus J, Dienel S, Nagy A, et al. Why Can’t Rodents Vomit? A Comparative Behavioral, Anatomical, and Physiological Study. Covasa M, editor. PLoS One [Internet], 2013 Apr 10;8(4):e60537. Available from: https: / / dx.plos.org / 10.1371 / joumal.pone.0060537 31. Cloutier CJ, Zevy DL, Kavaliers M, Ossenkopp KP. Conditioned disgust in rats (anticipatory nausea) to a context paired with the effects of the toxin LiCl: Influence of sex and the estrous cycle. Pharmacol Biochem Behav [Internet], 2018 Oct;173:51-7. Available from: https: / / linkinghub.elsevier.com / retrieve / pii / S0091305718302211 32. Yamamoto K, Tatsutani S, Ishida T. Detection of nausea-like response in rats by monitoring facial expression. Front Pharmacol [Internet], 2017 Jan 10;7(JAN). Available from: http: / / joumal.frontiersin.org / article / 10.3389 / fphar.2016.00534 / full 33. Andrews PLR, Hom CC. Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases. 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Early Intervention and Lifelong Treatment with GLP1 Receptor Agonist Liraglutide in a Wolfram Syndrome Rat Model with an Emphasis on Visual Neurodegeneration, Sensorineural Hearing Loss and Diabetic Phenotype. Vol. 10, Cells. 2021. 38. Jangra A, Gola P, Singh J, Gond P, Ghosh S, Rachamalla M, Dey A, Iqbal D, Kamal M, Sachdeva P, Jha SK, Ojha S, Kumar D, Jha NK, Chopra H, Tan SC. Emergence of taurine as a therapeutic agent for neurological disorders. Neural Regen Res. 2024 Jan; 19(1):62-68. doi: 10.4103 / 1673-5374.374139. PMID: 37488845; PMCID: PMC10479846. 39. Kanoski SE, Rupprecht LE, Fortin SM, De Jonghe BC, Hayes MR. The role of nausea in food intake and body weight suppression by peripheral GLP-1 receptor agonists, exendin-4 and liraglutide. Neuropharmacology [Internet], 2012 Apr;62(5-6): 1916-27. Available from: https: / / linkinghub.elsevier.com / retrieve / pii / S002839081100579X 40. Chandra Gupta R, Win T, Bittner S. Taurine Analogues: A New Class of Therapeutics. In: Frontiers in Medicinal Chemistry - (Volume 4) [Internet], BENTHAM SCIENCE PUBLISHERS; 2012. p. 183-213. Available from: http: / / www.eurekaselect.com / node / 53928 41. Plaas M, Seppa K, Reimets R, Jagomae T, Toots M, Koppel T, et al. Wfsl- deficient rats develop primary symptoms of Wolfram syndrome: insulin-dependent diabetes, optic nerve atrophy and medullary degeneration. Sci Rep [Internet], 2017;7(l): 10220. Available from: https: / / doi.org / 10.1038 / s41598-017-09392-x It is understood that the disclosed method and compositions are not limited to the particular methodology, protocols, and reagents described as these can vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention which will be limited only by the appended claims. Disclosed are materials, compositions, and components that can be used for, can be used in conjunction with, can be used in preparation for, or are products of the disclosed method and compositions. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds may not be explicitly disclosed, each is specifically contemplated and described herein. For example, if a HTL-GIDR is disclosed and discussed and a number of modifications that can be made to a number of molecules including the HTL-GIDR are discussed, each and every combination and permutation of HTL-GIDR and the modifications that are possible are specifically contemplated unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited, each is individually and collectively contemplated. Thus, is this example, each of the combinations A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are specifically contemplated and should be considered disclosed from disclosure of A, B, and C; D, E, and F; and the example combination A-D. Likewise, any subset or combination of these is also specifically contemplated and disclosed. Thus, for example, the sub-group of A-E, B-F, and C-E are specifically contemplated and should be considered disclosed from disclosure of A, B, and C; D, E, and F; and the example combination A-D. Further, each of the materials, compositions, components, etc. contemplated and disclosed as above can also be specifically and independently included or excluded from any group, subgroup, list, set, etc. of such materials. These concepts apply to all aspects of this application including, but not limited to, steps in methods of making and using the disclosed compositions. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the disclosed methods, and that each such combination is specifically contemplated and should be considered disclosed. Throughout the description and claims of this specification, the word “comprise” and variations of the word, such as “comprising” and “comprises,” means “including but not limited to,” and is not intended to exclude, for example, other additives, components, integers or steps. “Optional” or “optionally” means that the subsequently described event, circumstance, or material may or may not occur or be present, and that the description includes instances where the event, circumstance, or material occurs or is present and instances where it does not occur or is not present. Unless the context clearly indicates otherwise, use of the word “can” indicates an option or capability of the object or condition referred to. Generally, use of “can” in this way is meant to positively state the option or capability while also leaving open that the option or capability could be absent in other forms or embodiments of the object or condition referred to. Unless the context clearly indicates otherwise, use of the word “may” indicates an option or capability of the object or condition referred to. Generally, use of “may” in this way is meant to positively state the option or capability while also leaving open that the option or capability could be absent in other forms or embodiments of the object or condition referred to. Unless the context clearly indicates otherwise, use of “may” herein does not refer to an unknown or doubtful feature of an object or condition. Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, also specifically contemplated and considered disclosed is the range from the one particular value and / or to the other particular value unless the context specifically indicates otherwise. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another, specifically contemplated embodiment that should be considered disclosed unless the context specifically indicates otherwise. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint unless the context specifically indicates otherwise. It should be understood that all of the individual values and sub-ranges of values contained within an explicitly disclosed range are also specifically contemplated and should be considered disclosed unless the context specifically indicates otherwise. Finally, it should be understood that all ranges refer both to the recited range as a range and as a collection of individual numbers from and including the first endpoint to and including the second endpoint. In the latter case, it should be understood that any of the individual numbers can be selected as one form of the quantity, value, or feature to which the range refers. In this way, a range describes a set of numbers or values from and including the first endpoint to and including the second endpoint from which a single member of the set (i.e. a single number) can be selected as the quantity, value, or feature to which the range refers. The foregoing applies regardless of whether in particular cases some or all of these embodiments are explicitly disclosed. In one embodiment, “about” may mean ± 10%, or ± 5%, or ± 1%. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of skill in the art to which the disclosed method and compositions belong. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present method and compositions, the particularly useful methods, devices, and materials are as described. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such disclosure by virtue of prior invention. No admission is made that any reference constitutes prior art. The discussion of references states what their authors assert, and applicants reserve the right to challenge the accuracy and pertinency of the cited documents. It will be clearly understood that, although a number of publications are referred to herein, such reference does not constitute an admission that any of these documents forms part of the common general knowledge in the art. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the method and compositions 5 described herein. Such equivalents are intended to be encompassed by the following claims.

Claims

1. A homotaurine-like gastrointestinal distress-relieving (HTL-GIDR) composition for use in a method of treatment, wherein the method reduces one or more gastrointestinal side effects of glucagon-like peptide-1 (GLP-1) receptor agonist (RA) therapy, the method comprising administering said HTL-GIDR composition to a subject receiving GLP-1 RA therapy.

2. The composition for use in a method of treatment according to claim 1, wherein the one or more gastrointestinal side effects that are reduced are selected from the group consisting of: nausea, vomiting, loss of appetite, weight loss, weight gain, and constipation.

3. The composition for use in a method of treatment according to claim 1 or claim 2, wherein the HTL-GIDR composition comprises homotaurine or a homotaurine analog, or a combination thereof.

4. The composition for use in a method of treatment according to claim 3, wherein the HTL-GIDR composition comprises: homotaurine, acamprosate calcium, valiltramiprosate (ALZ-801), 3-sulfopropanoic acid, ethanesulfonic acid, piperidine-4-sulfonic acid, 3-Pyridine sulfonic acid, tauropine, gabamide, N-acetyltaurine, taurine-O-sulfonic acid, hypotaurine, or a combination thereof.

5. The composition for use in a method of treatment according to claim 3, wherein the HTL-GIDR composition comprises: homotaurine, acamprosate calcium, valiltramiprosate, 3-sulfopropanoic acid, or a combination thereof.

6. The composition for use in a method of treatment according to any one of claims 1-5, wherein the HTL-GIDR composition does not comprise taurine.

7. The composition for use in a method of treatment according to any one of claims 1-6, wherein the amount of the HTL-GIDR is the human equivalent dosage of a dosage sufficient to increase appetite in rats receiving liraglutide.

8. The composition for use in a method of treatment according to any one of claims 1-6, wherein the amount of the HTL-GIDR is the human equivalent dosage of a dosage sufficient to reduce weight loss in rats receiving liraglutide.

9. The composition for use in a method of treatment according to any one of claims 1-6, wherein the amount of the HTL-GIDR is the human equivalent dosage of a dosage sufficient to prevent weight loss in rats receiving liraglutide.

10. The composition for use in a method of treatment according to any one of claims 1-6, wherein the amount of the HTL-GIDR is the human equivalent dosage of a dosage of theHTL-GIDR sufficient to reduce one or more GLP-1 RA therapy induced negative side effects in rats receiving liraglutide.

11. The composition for use in a method of treatment according to claim 10, wherein the one or more GLP-1 RA therapy induced negative side effects are nausea, vomiting, constipation, or combinations thereof.

12. The composition for use in a method of treatment according to any one of claims 7-11, wherein the dosage sufficient to increase appetite in rats receiving liraglutide is able to rescue liraglutide induced abnormal feeding and drinking behavior in rats that had been habituated to drink cherry juice while receiving saline injections.

13. The composition for use in a method of treatment according to any one of claims 1-12, wherein the HTL-GIDR composition is in a unit dose formulation.

14. The composition for use in a method of treatment according to any one of claims 1-13, wherein the HTL-GIDR composition is formulated for oral or parenteral administration.

15. The composition for use in a method of treatment according to any one of claims 1-14, wherein the HTL-GIDR composition is administered orally, and the total daily dose of homotaurine or homotaurine analog that is administered to the subject is in the range from about 100 mg to about 3000 mg.

16. The composition for use in a method of treatment according to any one of claims 1-14, wherein the HTL-GIDR composition is administered via intraperitoneal (IP), intravenous (IV), or subcutaneous (SC) injection, and the total daily dosage of homotaurine or homotaurine analog that is administered to the subject is in the range from about 20 mg to about 600 mg.

17. The composition for use in a method of treatment according to any one of claims 1-16, wherein the GLP-1 RA therapy comprises administration of any medication whose therapeutic effect is to agonize the GLP1 receptor.

18. The composition for use in a method of treatment according to any one of claims 1-17, wherein the GLP-1 RA therapy comprises administration of: albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, tirzepatide, danuglipron, orforglipron, retatrutide, efpeglenatide, ALT-801, cotadutide, mazdutide, BI 456905, BI 456906, BI 442524, PF-07081532, SAR425899, TTP273, BAT1706, MN-850, APD334, CT-996, CT-388, DA-JC4, DA-CH5, XW003, NNC9204-1706, IMB-2024, SCO-267, NLY01, MK-8521, HM15211, DMB-3115, RG7697, RG7906, RG1067, or combinations thereof.

19. The composition for use in a method of treatment according to claim 18, wherein dulaglutide is used at a dosage of 0.75-1.5 mg / week, exenatide is used at a dosage of 10-20 pg / day, exenatide extended is used at a dosage of 2 mg / week, liraglutide is used at a dosage of0.6-3 mg / day, lixisenatide is used at a dosage of 10-20 pg / day, albiglutide is used a dosage of 30-50 mg / week, semaglutide is used at an oral dosage of 3-14 mg / day or an injection dosage of 0.25-1 mg / week, and / or tirzepatide is used at a dosage of 2.5-15 mg / week.

20. The composition for use in a method of treatment according to any one of claims 1-19, wherein (a) the HTL-GIDR composition is administered to the subject after the onset of said one or more side effects; or (b) the HTL-GIDR composition is administered to the subject concurrently with or in conjunction with one or more GLP-1 receptor agonists.

21. The composition for use in a method of treatment according to any one of claims 1-20, wherein the subject is receiving and tolerating a higher dosage of the GLP-1 RA therapy than the subject could tolerate in the absence of the administration of the HTL-GIDR composition.

22. The composition for use in a method of treatment according to claim 21, wherein the higher dosage of the GLP-1 RA therapy provides greater therapeutic effect to the subject.

23. The composition for use in a method of treatment according to any one of claims 1-22, wherein the subject has cancer, diabetes, neurodegeneration, excess body weight, incipient diabetes, risk of diabetes, cardiovascular disease, or risk of neurodegeneration.

24. The composition for use in a method of treatment according to any one of claims 1-23, wherein the subject is receiving the GLP-1 RA therapy as a treatment for cancer, diabetes, neurodegeneration, excess body weight, incipient diabetes, risk of diabetes, cardiovascular disease, or risk of neurodegeneration.

25. The composition for use in a method of treatment according to any one of claims 1-24, wherein the subject maintains a higher body weight than the subject would maintain in the absence of the administration of the HTL-GIDR composition.s

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