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Introduction: Type 2 diabetes (T2DM) and obesity present significant global health issues, requiring the development of long-lasting and highly effective pharmacotherapies. Although glucagon-like peptide-1 receptor agonists (GLP-1...
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Introduction: Type 2 diabetes (T2DM) and obesity present significant global health issues, requiring the development of long-lasting and highly effective pharmacotherapies. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used for diabetes treatment, their potential for addressing obesity is still being explored. Areas covered: This review offers a comprehensive overview of recently published patents from January 2020 to July 2023, focusing on modified GLP-1 RAs, small molecule GLP-1 RAs, GLP-1 R-based multi-agonists, GLP-1 RA-based fusion proteins, and combination therapies. The patents discussed pertain to the treatment and prevention of diabetes and obesity. Patent searches were conducted using the PATENTSCOPE database of the World Intellectual Property Organization, using the keywords GLP-1, GLP-1/GIP, GLP-1/GCG, and GLP-1 /GCG/GIP. Expert opinion: In recent years, patents have emphasized two main goals for developing GLP-1 RAs drugs: oral delivery and improved weight reduction effects. To address the growing demand for improved treatments, researchers have focused their efforts on developing GLP-1 R-based multi-agonists, orally administered GLP-1 RAs, and combination therapies utilizing GLP-1 RAs. These new approaches offer promising benefits, such as improved effectiveness by targeting multiple pathways and reduced side effects. Additionally, the development of new uses, oral forms, and long-lasting preparations will be crucial in shaping the future market potential of GLP-1 drugs.
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Aims/Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RA) might be less effective in patients with severe hyperglycemia, because hyperglycemia downregulated the GLP-1 receptor in an animal study. To examine this hypot...
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Aims/Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RA) might be less effective in patients with severe hyperglycemia, because hyperglycemia downregulated the GLP-1 receptor in an animal study. To examine this hypothesis clinically, we compared the glucose-lowering effects of GLP-1 receptor agonist liraglutide with and without prior glycemic control. Materials and Methods In an open-label, parallel trial, participants with poorly controlled type?2 diabetes were recruited and randomized to receive once-daily insulin therapy, degludec (Insulin–GLP-1 RA relay group, mean 16.8?±?11.4?IU/day), for 12?weeks and then liraglutide for 12?weeks or subcutaneous injections of GLP-1 RA, liraglutide (GLP-1 RA first group, 0.9?mg), for 24?weeks. The primary efficacy end-points consisted of changes in the levels of fasting plasma glucose and glycated hemoglobin (HbA1c). Results The median fasting plasma glucose and HbA1c before the study were 210.0?mg/dL and 9.8%, respectively. The levels of fasting plasma glucose and HbA1c significantly decreased in the Insulin–GLP-1 RA relay group ( P <?0.001) and GLP-1 RA first group ( P <?0.001) by week?24, although no intergroup differences were observed. The reduction of HbA1c in the Insulin–GLP-1 RA relay group tended to be larger than that in the GLP-1 RA first group in the lowest CPR (C-peptide immunoreactivity) quartile ( P =?0.072). The adverse events consisted of gastrointestinal problems, followed by hypoglycemia. Conclusions The GLP-1 receptor agonist is overall effective without prior glycemic control with insulin in participants with poorly controlled type?2 diabetes. However, in participants with insulinopenic type?2 diabetes, prior glycemic control with insulin might overcome glucose toxicity-induced GLP-1 resistance.
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? The Author(s) 2024.Introduction: Glucagon-like peptide-1 receptor agonist use has increased over the last decade for glycemic control in type 2 diabetes mellitus, cardiovascular risk reduction, and weight loss. Clinical trials i...
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? The Author(s) 2024.Introduction: Glucagon-like peptide-1 receptor agonist use has increased over the last decade for glycemic control in type 2 diabetes mellitus, cardiovascular risk reduction, and weight loss. Clinical trials indicate that gastrointestinal adverse effects are commonly experienced and severe hypoglycemia is rare; however, there is little data regarding glucagon-like peptide-1 receptor agonist in overdose. Methods: We performed a retrospective chart review evaluating and characterizing glucagon-like peptide-1 receptor agonist exposures reported to a single poison center between 2006 and 2023. Patient demographics, circumstances of exposure, clinical effects, and outcomes were abstracted from charts. Descriptive statistics were utilized to summarize demographic information and clinical factor data. Results: A total of 152 charts met inclusion criteria. Therapeutic errors accounted for 91% of exposures. Most patients (67%) reported no symptoms, although not all patients were followed to a definitive outcome. Nausea, vomiting, generalized weakness, and abdominal pain were the predominant symptoms reported. Most patients (62%) were monitored and closely followed in the home setting. Hypoglycemia was rare but occurred in the setting of a single agent glucagon-like peptide-1 receptor agonist exposure in two patients. Two additional patients who developed hypoglycemia involved co-administration of insulin. 21% of the exposures were related to errors on initial use of the pen. Conclusion: Exposures to glucagon-like peptide-1 receptor agonist have increased substantially over the years. Effects from an exposure tended to be mild and primarily involve gastrointestinal symptoms. Hypoglycemia was rare. Therapeutic and administration errors were common. Education on pen administration may help to reduce errors.
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Objective. This study aimed to investigate the benefits of exendin-4 treatment on brown adipose tissue (BAT) in C57BL/6J mice with high-fat diet (HFD)-induced obesity. Methods. We examined the effects of exendin-4 on body adiposit...
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Objective. This study aimed to investigate the benefits of exendin-4 treatment on brown adipose tissue (BAT) in C57BL/6J mice with high-fat diet (HFD)-induced obesity. Methods. We examined the effects of exendin-4 on body adiposity and the level of genes associated with adipogenesis, glucose/lipid uptake, lipolysis, and thermogenesis in mice with diet-induced obesity. Results. Exendin-4 treatment deceased body weight, serum-free fatty acid, and triglyceride levels in HFD-induced obese C57BL/6J mice. Exendin-4 treatment increased the expression of genes associated with adipogenesis, glucose/lipid uptake, lipolysis, and thermogenesis in BAT. Compared with HFD-fed mice, exendin-4 treatment also exhibited elevated energy expenditure and reduced respiratory quotient, but showed similar food intake and locomotor activity. Conclusions. Exendin-4 treatment reduced high-fat-induced obesity by decreasing adiposity and increasing thermogenesis. This result suggests that GLP-1 agonist may be a new approach to combat obesity by shifting the energy balance from obesogenesis to thermogenesis.
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Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA) has been associated with cholelithiasis in a previous meta-analysis. The publication of new trials suggests the need for an update. We collected trials with GLP1-RA vs. other the...
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Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA) has been associated with cholelithiasis in a previous meta-analysis. The publication of new trials suggests the need for an update. We collected trials with GLP1-RA vs. other therapies, calculating Mantel-Haenszel odds ratio (MH-OR, 95%CI). GLP1-RA significantly increased the risk of cholelithiasis (MH-OR 1.28 [1.11, 1.48]). (C) 2020 Elsevier B.V. All rights reserved.
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Glucagon-like peptide-1 (GLP-1), an incretin hormone, is known to lower glucose levels, suppress glucagon secretion, and slow gastric emptying. These properties make GLP-1 an ideal target in treating type 2 diabetes mellitus (T2DM...
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Glucagon-like peptide-1 (GLP-1), an incretin hormone, is known to lower glucose levels, suppress glucagon secretion, and slow gastric emptying. These properties make GLP-1 an ideal target in treating type 2 diabetes mellitus (T2DM). There are many FDA-approved GLP-1 agonists on the market today, several of which have demonstrated benefit beyond improving glycemic control. Given the beneficial effects of GLP-1 agonists in patients with T2DM, new drugs are in development that combine the mechanism of action of GLP-1 receptor agonism with novel mechanisms and with drugs that promote GLP-1 secretion. These agents are designed to improve glycemic control and target greater body weight reduction. This article discusses new GLP-1 drugs in the pipeline for the treatment of T2DM. ? The Author(s) 2021.
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Introduction: Obesity is a global epidemic with important healthcare and financial implications. Most current antiobesity pharmacological therapies are unsatisfactory due to undesirable side effects. Many drugs have been withdrawn...
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Introduction: Obesity is a global epidemic with important healthcare and financial implications. Most current antiobesity pharmacological therapies are unsatisfactory due to undesirable side effects. Many drugs have been withdrawn due to safety concerns. Maintaining weight loss remains the Achilles' heel of antiobesity therapy.Areas covered: This is an overview of the use of liraglutide for obesity treatment. Clinical efficacy on weight, cardiovascular parameters, as well as safety and tolerability issues are discussed.Expert opinion: Liraglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist, which has a protracted pharmacokinetic profile compared to native GLP-1 while maintaining its biological activity. It induces weight loss by reducing appetite and energy intake. It stimulates insulin release and decreases glucagon secretion in response to hyperglycaemia. Treatment with liraglutide, in addition with diet and exercise, induces sustained mean weight loss of 7.6 kg at 2 years (weight loss induced by orlistat = 5.7 kg, phentermine/topiramate controlled release 15/92 = 10.9 kg). It reduces blood pressure and improves glycaemic control, which has clinically relevant significance on reducing obesity-related morbidity and mortality. Liraglutide is reasonably well tolerated with gastrointestinal side effects being most commonly encountered. Novo Nordisk filed for regulatory approval of liraglutide 3.0 mg for obesity treatment in December 2013.
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Lixisenatide, a glucagon-like peptide-1 receptor agonist, is used to stimulate insulin secretion in patients with type 2 diabetes mellitus. However, its effect on insulin secretion in cancer patients, particularly during the cache...
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Lixisenatide, a glucagon-like peptide-1 receptor agonist, is used to stimulate insulin secretion in patients with type 2 diabetes mellitus. However, its effect on insulin secretion in cancer patients, particularly during the cachexia course, has not yet been evaluated. The purpose of this study was to investigate the lixisenatide effect on INS secretion decline during the cachexia course (2, 6, and 12 days of tumor) in pancreatic islets isolated from Walker-256 tumor-bearing rats. Pancreatic islets of healthy and tumor-bearing rats were incubated in the presence or absence of lixisenatide (10 nM). Tumor-bearing rats showed reduction of body weight and fat and muscle mass, characterizing the development of cachexia, as well as reduction of insulinemia and INS secretion stimulated by glucose (5.6, 8.3, 11.1, 16.7, and 20 mM) on days 2, 6, and/or 12 of tumor. Lixisenatide increased the 16.7 mM glucose-stimulated insulin secretion, but not by 5.6 mM glucose, in the islets of healthy rats, without changing the insulin intracellular content. However, lixisenatide did not prevent the decreased 16.7 mM glucose-stimulated insulin secretion in the pancreatic islets of rats with 2, 6, and 12 days of tumor and neither the decreased insulin intracellular content of rats with 12 days of tumor. In consistency, in vivo treatment with lixisenatide (50 mu g kg(-1), SC, once daily, for 6 days) visually increased insulinemia of healthy fasted rats, but did not prevent hypoinsulinemia of tumor-bearing rats. In conclusion, Walker-256 tumor-bearing rats showed early decline (2 days of tumor) of insulin secretion, which followed the cachexia course (6 and 12 days of tumor) and was not improved by lixisenatide, evidencing that this insulin secretagogue, used to treat type 2 diabetes, does not have beneficial effect in cancer bearing-rats.
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