GLP-1a: Going beyond Traditional Use (original) (raw)
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Glucagon-like peptide 1 (GLP-1)
Molecular Metabolism, 2019
Background: The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent b-cell proliferation. GLP-1 also has cardio-and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability. Biochemically modified for enhanced potency and sustained action, GLP-1 receptor agonists are successfully in clinical use for the treatment of type-2 diabetes, and several GLP-1-based pharmacotherapies are in clinical evaluation for the treatment of obesity. Scope of review: In this review, we provide a detailed overview on the multifaceted nature of GLP-1 and its pharmacology and discuss its therapeutic implications on various diseases. Major conclusions: Since its discovery, GLP-1 has emerged as a pleiotropic hormone with a myriad of metabolic functions that go well beyond its classical identification as an incretin hormone. The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders
Ali chtatbi , 2024
Glucagon-like receptor agonists for peptides 1 and 1 (GLP-1RA), including semaglutide and liraglutide, have become transformative treatments for obesity and type 2 diabetes, promising significant weight loss and glycemic control. However, these benefits come with substantial risks that are often underreported. This meta-analysis synthesizes evidence on adverse effects such as muscle mass reduction, psychiatric disturbances, and potential long-term health implications. Emerging studies suggest that GLP-1RAs can cause significant muscle loss, including cardiac muscle, potentially leading to exercise intolerance and frailty. In addition, concerns about increased rates of depression, anhedonia, and suicidal ideation highlight the need for careful monitoring and customized therapeutic strategies. This paper underscores the importance of balancing the metabolic benefits of GLP-1RA with their long-term systemic and psychological risks, advocating a more nuanced approach to the management of obesity.
GLP-1: benefits beyond pancreas
Journal of Endocrinological Investigation, 2014
Introduction Glucagon-like peptide 1 (GLP-1) is an intestinal hormone secreted after the ingestion of various nutrients. The main role of GLP-1 is to stimulate insulin secretion in a glucose-dependent manner. However, the expression of GLP-1 receptor was found to be expressed in a variety of tissues beyond pancreas such as lung, stomach, intestine, kidney, heart and brain. Beyond pancreas, a beneficial effect of GLP-1 on body weight reduction has been shown, suggesting its role for the treatment of obesity. In addition, GLP-1 has been demonstrated to reduce cardiovascular risk factors and to have a direct cardioprotective effect, fostering heart recovery after ischemic injury. Further, data from both experimental animal models and human studies have shown beneficial effect of GLP-1 on bone metabolism, either directly or indirectly on bone cells. Materials and methods We review here the recent findings of the extra-pancreatic effects of GLP-1 focusing on both basic and clinical studies, thus opening future perspectives to the use of GLP-1 analogs for the treatment of disease beyond type 2 diabetes. Conclusion Finally, the GLP-1 has been demonstrated to have a beneficial effect on both vascular, degenerative diseases of central nervous system and psoriasis.
Metabolic and cardiovascular benefits of GLP‑1 agonists, besides the hypoglycemic effect (Review)
Experimental and Therapeutic Medicine, 2020
Patients with type 2 diabetes exhibit higher cardiovascular risk than normal individuals. Optimal blood glucose levels are rarely achieved in diabetic patients. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a new antidiabetic drug class with multiple metabolic effects. Some trials have evaluated their safety, but it has been recently demonstrated that this new class has cardiovascular benefits, through other mechanisms than glycemic control. The use of GLP-1RAs was associated with a significant reduction of cardiovascular and all-cause mortality, with a safe profile related to pancreatitis or thyroid cancer, as compared with placebo. This review presents the cardiovascular and metabolic benefits of GLP-1 RAs versus placebo, in patients with type 2 diabetes. Semaglutide and liraglutide demonstrated a reduction in cardiovascular events, with similar rates on cardiovascular mortality. Ongoing trials assess the cardiovascular benefits and side effects of dulaglutide treatment. Exenatide and liraglutide demonstrated the decrease of blood pressure values, weight reduction and improvement of dyslipidemia. Liraglutide induced, both in vivo and in vitro, an improvement of blood circulation, increasing the nitric oxide level and inhibiting the adhesion and procoagulant factors. Also, liraglutide demonstrated beneficial effects on cardiac remodeling after myocardial infarction, but more large trials are required. However, the international guidelines recommend using GLP-1 RAs as first-line therapy in type 2 diabetes patients with high cardiovascular risk or as first-line agents in patients intolerant to metformin. Contents 1. Introduction 2. Mechanism of action of GLP-1 hormone and its pleiotropic effects 3. Evidence of cardiovascular effects of GLP-1 agonists 4. Evidence of GLP-1 agonists on metabolism 5. Conclusions
Neural effects of gut‐ and brain‐derived glucagon‐like peptide‐1 and its receptor agonist
Journal of Diabetes Investigation, 2016
Glucagon-like peptide-1 (GLP-1) is derived from both the enteroendocrine L cells and preproglucagon-expressing neurons in the nucleus tractus solitarius (NTS) of the brain stem. As GLP-1 is cleaved by dipeptidyl peptidase-4 yielding a half-life of less than 2 min, it is plausible that the gut-derived GLP-1, released postprandially, exerts its effects on the brain mainly by interacting with vagal afferent neurons located at the intestinal or hepatic portal area. GLP-1 neurons in the NTS widely project in the central nervous system and act as a neurotransmitter. One of the physiological roles of brain-derived GLP-1 is restriction of feeding. GLP-1 receptor agonists have recently been used to treat type 2 diabetic patients, and have been shown to exhibit pleiotropic effects beyond incretin action, which involve brain functions. GLP-1 receptor agonist administered in the periphery is stable because of its resistance to dipeptidyl peptidase-4, and is highly likely to act on the brain by passing through the blood-brain barrier (BBB), as well as interacting with vagal afferent nerves. Central actions of GLP-1 have various roles including regulation of feeding, weight, glucose and lipid metabolism, cardiovascular functions, cognitive functions, and stress and emotional responses. In the present review, we focus on the source of GLP-1 and the pathway by which peripheral GLP-1 informs the brain, and then discuss recent findings on the central effects of GLP-1 and GLP-1 receptor agonists.
From Theory to Clinical Practice in the Use of GLP-1 Receptor Agonists and DPP-4 Inhibitors Therapy
Experimental Diabetes Research, 2011
Promoting long-term adherence to lifestyle modification and choice of antidiabetic agent with low hypoglycemia risk profile and positive weight profile could be the most effective strategy in achieving sustained glycemic control and in reducing comorbidities. From this perspective, vast interest has been generated by glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 inhibitors (DPP-4i). In this review our ten-year clinical and laboratory experience by in vitro and in vivo studies is reported. Herein, we reviewed available data on the efficacy and safety profile of GLP-1 receptor agonists and DPP-4i. The introduction of incretin hormone-based therapies represents a novel therapeutic strategy, because these drugs not only improve glycemia with minimal risk of hypoglycemia but also have other extraglycemic beneficial effects. In clinical studies, both GLP-1 receptor agonists and DPP-4i, improve β cell function indexes. All these agents showed trophic effects on beta-cell mass in animal studies. The use of these drugs is associated with positive or neucral effect on body weight and improvements in blood pressure, diabetic dyslipidemia, hepatic steazosis markets, and myocardial function. These effects have the potential to reduce the burden of cardiovascular disease, which is a major cause of mortality in patients with diabetes.
Current Issues in GLP-1 Receptor Agonist Therapy for Type 2 Diabetes
Endocrine Practice, 2012
Abbreviations: A1C = glycated hemoglobin; ABCD = Association of British Clinical Diabetologists; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BID = twice daily; BMI = body mass index; BNP = brain natriuretic peptide; CIs = confidence intervals; CrCl = creatinine clearance; DAWN Trial = Diabetes Attitudes, Wishes and Needs Trial; DPP-4 = dipeptidyl peptidase-4; DTSQ-s: Diabetes Treatment Satisfaction Questionnairestatus; EASD = European Association for the Study of Diabetes; ER = extended release; ESRD = end-stage renal disease; EXN = exenatide; FAERS = FDA Adverse Event Reporting System; FDA = United States Food and Drug Administration; FPG = fasting plasma glucose; GI = gastrointestinal; GIP = glucosedependent insulinotropic polypeptide; GLAR = insulin glargine; GLP-1 = glucagon-like peptide-1; GLP-1 RA = glucagon-like peptide-1 receptor agonist; HOMA-B: homeostatic model assessment-β-cell function; HRQL = healthrelated quality of life; hs-CRP = high-sensitivity C-reactive protein; IDET = insulin detemir; IMT = intima-media thickness; IWQOL-Lite: Impact of Weight on Quality of Life-Lite; LEAD Trials = Liraglutide Effect and Action in Diabetes Trials; LIRA = liraglutide; MEN 2 = multiple endocrine neoplasia syndrome type 2; MET = metformin; MTC = medullary thyroid carcinoma; NAFLD = nonalcoholic fatty liver disease; NASH = nonalcoholic steatohepatitis; NICE = National Institute for Clinical Excellence; NIH = National Institutes of Health; OAD = oral antidiabetic agent; PAI-1 = plasminogen activator inhibitor-1; PBO = placebo; PPG = postprandial glucose; PROs = patient-reported outcomes; RA = receptor agonist; RCT = randomized controlled trial; RI = renal impairment; RORs = reporting odds ratios; SCALE = Satiety and Clinical Adiposity -Liraglutide Evidence in Non-Diabetic and Diabetic Subjects; STEMI = ST segment elevation myocardial infarction; SU = sulfonylurea; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus; TZD = thiazolidinedione
Emerging Role of GLP-1 Agonists in Obesity: A Comprehensive Review of Randomised Controlled Trials
International Journal of Molecular Sciences
Obesity is a chronic disease with high prevalence and associated comorbidities, making it a growing global concern. These comorbidities include type 2 diabetes, hypertension, ventilatory dysfunction, arthrosis, venous and lymphatic circulation diseases, depression, and others, which have a negative impact on health and increase morbidity and mortality. GLP-1 agonists, used to treat type 2 diabetes, have been shown to be effective in promoting weight loss in preclinical and clinical studies. This review summarizes numerous studies conducted on the main drugs in the GLP-1 agonists class, outlining the maximum achievable weight loss. Our aim is to emphasize the active role and main outcomes of GLP-1 agonists in promoting weight loss, as well as in improving hyperglycemia, insulin sensitivity, blood pressure, cardio–metabolic, and renal protection. We highlight the pleiotropic effects of these medications, along with their indications, contraindications, and precautions for both diabeti...