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April 5, 2026New England Journal of Medicine47 citations

GLP-1 Receptor Agonists

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CRClifford J. RosenJIJulie R. Ingelfinger

Key Points

  • To explore the effects of GLP-1 receptor agonists on glucose metabolism, weight management, and cardiovascular health.
  • Overview of GLP-1 receptor agonists and their mechanisms of action.
  • Review of random controlled trials assessing cardiovascular outcomes and weight loss.
  • Discussion on adverse effects and long-term adherence issues.
  • GLP-1 receptor agonists promote insulin release and weight loss through various mechanisms.
  • They significantly reduce cardiovascular risk and slow progression to renal failure in high-risk populations.
  • Gastrointestinal side effects are common, with concerns about muscle and bone mass loss.

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.

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Cite This Study

Rosen et al. (2026) studied this question.

synapsesocial.com/papers/69d1fb20a79560c99a0a1946https://doi.org/10.1056/nejmra2500106
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