FDA Grants MACE Reduction Indication for Semaglutide

Semaglutide injection (Wegovy; Novo Nordisk) now has an additional indication for the reduction of major adverse cardiovascular events in adults with established CVD and either overweight or obesity, according to a Friday announcement from the US Food and Drug Administration.

Already approved for chronic weight management as an adjunct to diet and exercise, semaglutide becomes the first medication indicated to reduce cardiovascular events specifically in adults with overweight or obesity and established CVD, the FDA said.

The agency’s decision was supported by findings from the placebo-controlled SELECT trial, which showed that the glucagon-like peptide-1 (GLP-1) receptor agonist—given on top of standard therapy—significantly reduced the risk of CV death, MI, or stroke (6.5% vs 8.0%; HR 0.80; 95% CI 0.72-0.90) in patients with established CVD, no prior history of diabetes, and a body mass index of at least 27 kg/m².

The exact mechanism of the CV risk reduction observed in the trial is unclear, Novo Nordisk said in a press release.

The FDA noted that the semaglutide label has a boxed warning about the risk of thyroid C-cell tumors, saying the drug shouldn’t be used in patients with a personal or family history of medullary thyroid carcinoma or in those with multiple endocrine neoplasia syndrome type 2. There are also a variety of other warnings regarding risks of acute pancreatitis, acute gallbladder disease, hypoglycemia, acute kidney injury, hypersensitivity reactions, diabetic retinopathy, increased heart rate, and suicidal behavior and ideation. Earlier this year, however, the agency released preliminary findings of a review that demonstrated no evidence of a link between GLP-1 receptor agonists and suicidal thoughts or actions.

Before Friday, semaglutide, which comes with well-known GI side effects, was already approved for chronic weight management in adults with overweight accompanied by at least one weight-related comorbidity, and in adults or pediatric patients 12 years and older with obesity.

Novo Nordisk said it has filed for an expanded MACE reduction indication in Europe as well, with a decision expected sometime this year.