The New England journal of medicine 2023 Nov 11
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes.
Abstract
Background
Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to reduce the risk of adverse cardiovascular events in patients with diabetes. Whether semaglutide can reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes is unknown.
Methods
In a multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial, we enrolled patients 45 years of age or older who had preexisting cardiovascular disease and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 27 or greater but no history of diabetes. Patients were randomly assigned in a 1:1 ratio to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis. Safety was also assessed.
Results
A total of 17,604 patients were enrolled; 8803 were assigned to receive semaglutide and 8801 to receive placebo. The mean (±SD) duration of exposure to semaglutide or placebo was 34.2±13.7 months, and the mean duration of follow-up was 39.8±9.4 months. A primary cardiovascular end-point event occurred in 569 of the 8803 patients (6.5%) in the semaglutide group and in 701 of the 8801 patients (8.0%) in the placebo group (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.90; P<0.001). Adverse events leading to permanent discontinuation of the trial product occurred in 1461 patients (16.6%) in the semaglutide group and 718 patients (8.2%) in the placebo group (P<0.001).
Conclusions
In patients with preexisting cardiovascular disease and overweight or obesity but without diabetes, weekly subcutaneous semaglutide at a dose of 2.4 mg was superior to placebo in reducing the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke at a mean follow-up of 39.8 months. (Funded by Novo Nordisk; SELECT ClinicalTrials.gov number, NCT03574597.).
Related Questions
Would you consider changing a non-diabetic patient with obesity and a history of CAD who is on semaglutide to tirzepatide if they have not achieved their weight loss goals?
For now, I would NOT switch a patient with any atherosclerotic cardiovascular disease from semaglutide to tirzepatide, assuming that they had a substantial response to semaglutide and was tolerating semaglutide well. The rationale is that cardiovascular event prevention would be the primary goal of ...
Should we be more cautious with the use of GLP 1 R agonist therapy in patients with Type 1 diabetes mellitus and obesity given the increased risk of cardiovascular disease with high body weight variability?
There doesn't seem to be any evidence that GLP-1 RA would increase the risk of CV disease. Biologically, the benefits that have been shown in patients without Diabetes (the SELECT trial) should still be applicable for patients with Diabetes Type 1.The trials that didn't show much efficacy in glucose...
Would it be reasonable to begin considering GLP1 RAs or finerenone for patients with heart failure with recovered LVEF in light of recent trials such as SELECT and FINEARTS-HF showing some success in HFpEF and HFmrEF populations?
I reject the premise of the question. Patients with HFrEF who improve on medical therapy do not become HFpEF. The pathophysiology of these diseases are entirely distinct and it speaks to the limitation of EF as a categorical variable. HFrEF patients have cardiomyopathy that manifests over time as di...
What are your top takeaways from AHA 2023?
SELECT trial ARIES-HM3 trial SPEC-AI trial