SUSTAIN-6

SUSTAIN-6 was designed as a safety trial and delivered a benefit finding. Regulators require new diabetes drugs to prove they do not increase cardiovascular risk; semaglutide cleared that bar and then went past it. The trial randomized 3,297 adults with type 2 diabetes — 83% of whom already had established cardiovascular disease, chronic kidney disease or both — to semaglutide or placebo. Marso and colleagues published it in the New England Journal of Medicine in 2016.

The primary composite of cardiovascular death, nonfatal heart attack and nonfatal stroke occurred in 6.6% of the semaglutide group versus 8.9% on placebo, a hazard ratio of 0.74. Nonfatal stroke drove much of it, falling from 2.7% to 1.6%. Cardiovascular death rates were similar between groups, and new or worsening kidney disease was less common on semaglutide.

One finding deserves more attention than it usually gets. Retinopathy complications — vitreous hemorrhage, blindness, or eye disease needing injection or laser treatment — were significantly more common on semaglutide, with a hazard ratio of 1.76. The leading explanation is that rapid improvement in long-standing high blood sugar can transiently worsen existing diabetic eye disease, a phenomenon known from insulin therapy. It is a reason to have your eyes examined before and during treatment, not a reason to avoid the drug.

The common confusion is applying this result to weight-management use. SUSTAIN-6 studied people with type 2 diabetes at high cardiovascular risk, at diabetes doses. The evidence for people with obesity and no diabetes comes from SELECT, a separate and much larger trial.

Worth asking your clinician: whether you have diabetic retinopathy now, whether a dilated eye exam should be scheduled before you start or escalate, and how fast your A1c is expected to fall. Our SUSTAIN-6 deep dive, cardiovascular study roundup, and Ozempic drug page cover the rest.