Curbing the Obesity Epidemic: Should GLP-1 Receptor Agonists Be the Standard of Care for Obesity?

This article summarizes the medical management of obesity with an emphasis on incretin-based therapeutics that target the neuro-hormonal basis of obesity. Medications that mimic the effect of incretins, a group of peptide hormones released in response to nutrient intake that regulate appetite, result in potent and durable weight loss. Glucagon-like peptide 1 (GLP-1) agonists and glucose-dependent insulinotropic polypeptide (GIP) agonists such as semaglutide and tirzepatide are approved by the United States Food and Drug Administration (FDA) for the management of obesity. The SELECT trial demonstrated that semaglutide led to a reduction in major adverse cardiovascular events in patients without diabetes who were either overweight and had preexisting cardiovascular disease or obese. The treatment of obesity is critical to prevent the progression of cardiovascular-kidney-metabolic syndrome. Incretin-based therapies offer remarkable weight loss and reduce major cardiovascular adverse events.

Kaplan JM ，Zaman A ，Abushamat LA 《-》

The dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide: a novel cardiometabolic therapeutic prospect.

Incretin hormones are peptides released in the intestine in response to the presence of nutrients in its lumen. The main incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 stimulates insulin secretion, inhibits glucagon secretion at pancreatic α cells and has also extrapancreatic influences as slowing of gastric emptying which increases the feeling of satiety. GIP is the main incretin hormone in healthy people, causative of most the incretin effects, but the insulin response after GIP secretion in type 2 diabetes mellitus (T2DM) is strongly reduced. Therefore, in the past GIP has been considered an unappealing therapeutic target for T2DM. This conception has been changing during recent years, since it has been reported that resistance to GIP can be reversed and its effectiveness restored by improving glycemic control. This fact paved the way for the development of a GIP receptor agonist-based therapy for T2DM, looking also for the possibility of finding a combined GLP-1/GIP receptor agonist. In this framework, the novel dual GIP and GLP-1 receptor agonist tirzepatide seems to be not just a new antidiabetic medication. Administered as a subcutaneous weekly injection, it is a manifold single pharmacological agent that has the ability to significantly lower glucose levels, as well as improve insulin sensitivity, reduce weight and amend dyslipidemia favorably modifying the lipid profile. Tirzepatide and additional dual GLP-1/GIP receptor agonists that could eventually be developed in the future seem to be a promising furthest advance for the management of several cardiometabolic settings. Obviously, it is too early to be overly hopeful since it is still necessary to determine the long-term effects of these compounds and properly verify the potential cardiovascular benefits. Anyway, we are currently facing a novel and very appealing therapeutic option.

Fisman EZ ，Tenenbaum A 《Cardiovascular Diabetology》

A Review of Incretin Therapies Approved and in Late-Stage Development for Overweight and Obesity Management.

Chetty AK ，Rafi E ，Bellini NJ ，Buchholz N ，Isaacs D ... -  《Endocrine Practice》

Role of glucagon-like peptide 1 receptor agonists in management of obesity.

Published data on the weight loss effects of glucagon-like peptide 1 (GLP-1) receptor agonists are reviewed, with a focus on data from clinical trials. Obesity is a significant health problem in the United States (an estimated 69% of U.S. adults are overweight and nearly 35% are obese), and few drugs have proven safety and efficacy as adjuncts to lifestyle modification for weight management. GLP-1 receptor agonists are used for glycemic control in patients with type 2 diabetes and have been studied for their weight loss effects in patients with and without diabetes; these agents produce weight loss benefits through their effects on satiety and gastric emptying. In December 2014, the liraglutide product Saxenda (Novo Nordisk) became the first GLP-1 receptor agonist approved by the Food and Drug Administration (FDA) for use in long-term weight management. Results of clinical trials that evaluated the effects of GLP-1 receptor agonist therapy on weight and body mass index indicated outcomes comparable or superior to those achieved with the use of other antiobesity agents. As a class, GLP-1 receptor agonists have a generally more favorable safety profile than several other antiobesity agents; transient, mild-to-moderate gastrointestinal symptoms were the most frequently reported adverse effects in clinical trials. Originally marketed for glycemic control in type 2 diabetes, GLP-1 receptor agonists have been found effective for weight reduction in patients with and without type 2 diabetes. Liraglutide is currently the only GLP-1 receptor agonist approved by FDA for obesity treatment.

Isaacs D ，Prasad-Reddy L ，Srivastava SB 《-》

Glucagon-like peptide-1 receptor agonists: the key to healthy weight loss maintenance?

Lehmann EW ，Torekov SS 《-》