GLP-1 Receptor Agonists

Document Type

Article

Publication Date

4-2-2026

Institution/Department

Center for Molecular Medicine

Journal Title

The New England journal of medicine

MeSH Headings

Humans; Cardiovascular Diseases (etiology, metabolism, prevention & control); Diabetes Mellitus, Type 2 (complications, drug therapy, metabolism); Glucagon-Like Peptide 1 (agonists, metabolism); Glucagon-Like Peptide-1 Receptor Agonists (adverse effects, pharmacology, therapeutic use); Hypoglycemic Agents (adverse effects, pharmacology, therapeutic use); Incretins (metabolism); Obesity (complications, drug therapy, metabolism); Renal Insufficiency (etiology, metabolism, prevention & control); Anti-Obesity Agents (adverse effects, pharmacology, therapeutic use); Disease Progression; Gastric Emptying (drug effects); Glucagon (metabolism); Gastrointestinal Microbiome (drug effects); Satiety Response (drug effects); Randomized Controlled Trials as Topic; Medication Adherence

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists are incretin analogues that promote glucose-mediated insulin release and are used to treat type 2 diabetes mellitus and obesity. GLP-1 receptor agonists and GLP-1 and glucose-dependent insulinotropic peptide agonists have several mechanisms of action, including reduction of gastric emptying, inhibition of glucagon secretion, beneficial changes in the intestinal microbiome, and direct effects on hypothalamic nuclei to enhance satiety (which promotes weight loss). Beyond the impressive effects of GLP-1 receptor agonists on blood glucose levels and body weight, large-scale randomized, controlled trials have shown that GLP-1 receptor agonists reduce cardiovascular risk and slow progression to renal failure in persons at high risk and those with type 2 diabetes. Adverse side effects from GLP-1 receptor agonists are mostly gastrointestinal but may also include loss of muscle and bone mass. Questions remain about long-term adherence, weight regain after discontinuation of treatment, and the functional implications of the loss of muscle and bone mass. Recent and ongoing targeted studies suggest the possibility of additional uses for GLP-1 receptor agonists.

First Page

1313

Last Page

1324

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