Semaglutide’s heart and kidney results

SELECT: cardiovascular events without diabetes

SELECT studied 17,604 adults with preexisting cardiovascular disease and overweight or obesity, without diabetes. Semaglutide reduced the primary composite of cardiovascular death, nonfatal heart attack or nonfatal stroke versus placebo: hazard ratio 0.80, with a 95% confidence interval of 0.72–0.90. The trial reported a 20% relative risk reduction.

A composite combines several outcomes into one trial measure; here, those outcomes were cardiovascular death, nonfatal heart attack and nonfatal stroke. The actual contents of that measure matter to me. They make this a different kind of result from a lower body weight.

My enthusiasm for SELECT has a specific address: the population it enrolled. SELECT persuaded me to treat the cardiovascular result as a central topic for that population. It cannot supply the same forecast for every person who is interested in weight loss. The word “relative” also matters: the 20% figure compares risks between the study groups. It does not state an individual’s absolute chance of an event.

Heart-failure symptoms

The STEP-HFpEF trial studied people with obesity-related heart failure with preserved ejection fraction. Semaglutide improved heart-failure-related symptoms and physical limitations and produced greater weight loss than placebo. The symptom and physical-limitation score gives this study a place in the story alongside the cardiovascular-event trials.

I am glad that physical limitations were measured. A paper asking about symptoms gets closer to the ordinary activities that a weight measurement alone leaves out. Physical limitations draw my interest toward an ordinary day and the ordinary things someone hopes to be able to do.

FLOW: type 2 diabetes and chronic kidney disease

FLOW enrolled 3,533 people with type 2 diabetes and chronic kidney disease. Its primary kidney composite included kidney failure, a decline of at least 50% in eGFR, or kidney or cardiovascular death. eGFR is an estimate of how well the kidneys filter blood. Semaglutide reduced that composite versus placebo: hazard ratio 0.76, with a 95% confidence interval of 0.66–0.88, described as a 24% lower risk.

The people studied had both type 2 diabetes and chronic kidney disease. The finding is already consequential with its actual population and outcomes left in place.

The diabetes trial’s eye finding

SUSTAIN-6 adds an uncomfortable piece of the picture. In people with type 2 diabetes at high cardiovascular risk, semaglutide reduced the composite cardiovascular outcome while diabetic-retinopathy complications were more frequent. Retinopathy is damage to the retina associated with diabetes.

That pairing is a reason for precision, and I think it improves the conversation. An encouraging cardiovascular result can coexist with a finding that needs clinical attention elsewhere. The safety review discusses retinopathy monitoring with rapid glycemic correction. The side-effects essay returns to that caution without turning an essay into a personal treatment plan.