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Invited Commentary
March 28, 2022

Glucagon-Like Peptide-1 Receptor Agonists—How Safe Are They?

Author Affiliations
  • 1Department of Internal Medicine, Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut
JAMA Intern Med. 2022;182(5):520-521. doi:10.1001/jamainternmed.2022.0335

A 64-year-old patient with long-standing type 2 diabetes and a history of myocardial infarction expressed frustration with his elevated blood glucose level and inability to lose weight. He was taking metformin but wondered if he needed another medication. We discussed treatment options and he became interested in starting treatment with a glucagon-like peptide-1 receptor agonist (GLP-1 RA), but he wanted to make sure it had a good track record of safety.

Glucagon-like peptide-1 receptor agonists have emerged as attractive therapies for patients with type 2 diabetes or obesity. For type 2 diabetes, GLP-1 RAs use has been shown to reduce levels of glycated hemoglobin (HbA1c; mean difference, −0.9% after 6 months) and promote weight loss (mean difference, −1.5 kg after 6 months).1 With obesity, GLP-1 RA use is associated with more substantial weight loss (mean difference, −12.7 kg after 68 weeks for semaglutide vs placebo).2 In addition, multiple trials have demonstrated that GLP-1 RA use in patients with type 2 diabetes was associated with reductions in major cardiovascular events, which appear to be unrelated to how GLP-1 RAs affect HbA1c levels.1 The relative effects of GLP-1 RAs on cardiovascular outcomes are consistent across patients with different levels of baseline risk for cardiovascular events; thus, the absolute effects are primarily driven by the patient’s individual risk. Accordingly, current guidelines for diabetes management recommend3 or suggest4 the use of GLP-1 RAs, irrespective of HbA1c levels, in individuals with type 2 diabetes at high risk for or with established atherosclerotic cardiovascular disease.

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