The blockbuster diabetes and weight reduction drug semaglutide (Wegovy, Ozempic, Rybelsus) decreased the relative danger of coronary heart assault, stroke, or cardiovascular deaths by 20 p.c in high-risk sufferers with heart problems however not diabetes throughout a big and lengthy randomized, placebo-controlled trial.
That general danger discount equates to fifteen fewer cardiovascular occasions per 1,000 sufferers handled. Individuals on semaglutide within the trial misplaced a median of 9.5 p.c of their physique weight, an 8.5 percentage-point drop over these within the placebo group.
The research, which was previewed in an August press launch by the drug’s maker and trial-runner Novo Nordisk, was printed in full Saturday within the New England Journal of Drugs, timed to a presentation of the findings on the American Coronary heart Affiliation convention in Philadelphia.
The outcomes have bolstered pleasure over semaglutide, with many saying it advances the drug as a brand new pharmaceutical weapon within the combat towards cardiovascular ailments, along with diabetes, weight problems, and obese—shedding any lingering notions of it being merely a way of life drug. The trial might sway extra insurance coverage suppliers to cowl the drug, which is costly. Wegovy—sematglutide used for weight reduction—has an inventory worth within the US of $1,349 monthly. Individuals within the trial had been on the drug for a median of round three years, which might carry a price ticket of $48,564.
Limitations
The trial has some notable caveats. Maybe the most important is that whereas the trial was massive, with 17,604 contributors, it didn’t enroll a various group of contributors. Most had been white (84 p.c) and male (72 p.c).
A requirement for getting into the trial was to have established heart problems and thus be at excessive danger of an occasion, corresponding to stroke, coronary heart assault, or cardiovascular-related loss of life. However the contributors on the entire didn’t have their baseline cardiovascular danger elements—like levels of cholesterol and blood strain—underneath management, which may be accomplished utilizing present instruments corresponding to statins and hypertension medicine. It is potential that the advantages of semaglutide might not have been as constructive as they had been if these underlying danger elements had been properly managed.
The trial additionally leaves looming the query of how semaglutide decreased the relative danger of cardiovascular occasions in sufferers with out diabetes. Was it merely the lack of weight, or was it one other motion of the drug, which mimics the metabolic hormone Glucagon-like peptide-1 (GLP-1) to extend insulin secretion, gradual abdomen emptying, and reduce urge for food? As two specialists from the College of Texas Southwestern Medical Heart and the Nationwide Institutes of Well being wrote in an accompanying editorial in NEJM, “It stays unclear to what diploma the trial findings had been depending on weight reduction, concomitant reductions in danger elements, or different salutary mechanisms of GLP-1 receptor agonism.”
The query is a essential one on condition that sufferers who go on the drug accomplish that for an indefinite interval, with the potential to regain the misplaced weight after stopping the drug.
Examine particulars
Of the 17,604 sufferers enrolled throughout 41 nations, 8,803 had been randomly assigned to obtain weekly subcutaneous injections of semaglutide, with 8,801 getting a placebo. The trial ran from October of 2018 to March of 20221. The sufferers’ imply age was 61, and the imply physique mass index was 33, falling within the class of weight problems. Negative effects, primarily gastrointestinal issues, led 1,461 sufferers (16.6 p.c) within the semaglutide group and 718 sufferers (8.2 p.c) within the placebo to discontinue their assigned intervention.
The trial primarily checked out a “composite finish level” of sufferers who had a cardiovascular-related loss of life, nonfatal coronary heart assault, or a nonfatal stroke. Within the semaglutide group, there have been 569 sufferers (6.5 p.c) who had not less than one in all these occasions, whereas there have been 701 (8 p.c) within the placebo group. This was the one statistically important discovering within the research.
Damaged down additional, the outcomes indicated a 15 p.c relative danger discount for cardiovascular deaths in these on semaglutide, however this was not statistically important. There additionally seemed to be a 28 p.c relative danger discount for coronary heart assault and a 7 p.c discount in danger of stroke, however the statistical significance of those findings was not calculated after deaths failed to fulfill the statistical threshold.
