Semaglutide already reduces cardiovascular events in people with diabetes, where the glucose lowering gives an obvious route to the benefit. Take diabetes out and the question reopens. So an enrolled 17,604 patients aged 45 or over who had existing cardiovascular disease and a of 27 or more, with no history of diabetes, and randomized them against placebo. What happened to the events?
The event rate fell by a fifth. A primary end-point event, meaning cardiovascular death, nonfatal myocardial infarction or nonfatal stroke, occurred in 569 of 8,803 patients on semaglutide, 6.5 percent, against 701 of 8,801 on placebo, 8.0 percent. The was 0.80, with a 95 percent interval from 0.72 to 0.90. Mean follow-up ran 39.8 months.
Semaglutide, a glucagon-like peptide-1 receptor agonist, had already been shown to reduce adverse cardiovascular events in patients with diabetes. In that population the mechanism is ambiguous, because the drug lowers glucose and glucose itself drives cardiovascular risk. Whether it reduces risk in overweight and obesity without diabetes was unknown.
The trial was multicenter, double-blind, randomized, placebo-controlled and event-driven, designed to test superiority. It enrolled patients 45 years of age or older with preexisting cardiovascular disease and a body-mass index of 27 kilograms per square meter or higher, excluding anyone with a history of diabetes. Assignment was one to one, to once-weekly subcutaneous semaglutide at 2.4 milligrams or placebo.
In total 17,604 patients enrolled, with 8,803 assigned to semaglutide and 8,801 assigned to placebo. Mean exposure to study drug ran 34.2 months and mean follow-up 39.8 months, so this is a multi-year result rather than a short one.
A event occurred in 569 patients on semaglutide, 6.5 percent, and in 701 on placebo, 8.0 percent. That gives a hazard ratio of 0.80, with a 95 percent interval from 0.72 to 0.90. The authors conclude semaglutide was superior to placebo for this composite endpoint. Note who was studied: everybody already had cardiovascular disease, which makes this secondary prevention in a high-risk group rather than evidence about healthy people.
wat. Weekly injections cut cardiovascular deaths, heart attacks and strokes from eight percent to six and a half over more than three years.
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The endpoint here is the one that matters: deaths, heart attacks and strokes, not a marker. It also separates the cardiovascular benefit from glucose control, since nobody enrolled had diabetes to begin with.
How do we know?
Lincoff and colleagues ran a multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial of once-weekly subcutaneous semaglutide at 2.4 milligrams against placebo, in patients with cardiovascular disease and overweight or obesity but no diabetes.
What is still unknown
Everyone enrolled already had cardiovascular disease and a raised body-mass index, so this is secondary prevention in high-risk people. It does not say what the drug does for someone without established heart disease.
Learn something?
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