The New England journal of medicineApr 3, 2026

Drugs that activate GLP-1 receptors

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 4, 2026

Abstract

GLP-1 receptor agonists are associated with reduced cardiovascular risk and slowed progression to renal failure in individuals with type 2 diabetes.

GLP-1 receptor agonists promote glucose-mediated insulin release and enhance satiety.
They reduce gastric emptying and inhibit glucagon secretion.
Beneficial changes in the intestinal microbiome may occur with GLP-1 receptor agonist use.
Adverse effects are primarily gastrointestinal, with potential loss of muscle and bone mass.
Long-term adherence and weight regain after stopping treatment remain concerns.

Simplified

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.

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Drugs that activate GLP-1 receptors

Abstract

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