Semaglutide

Current evidence

Semaglutide 2.4 mg weekly was compared with placebo plus usual care in SELECT among 17,604 adults with established cardiovascular disease and overweight or obesity, without diabetes. Major cardiovascular events occurred in 6.5% versus 8.0%. SELECT demonstrated fewer major cardiovascular events with semaglutide in adults with established cardiovascular disease and overweight/obesity without diabetes, alongside greater treatment discontinuation. SELECT's weight and kidney publications add endpoint-specific context from the same trial rather than new independent efficacy replications.

In FLOW, weekly semaglutide was compared with placebo in adults with type 2 diabetes and chronic kidney disease. Fewer people receiving semaglutide experienced the combined outcome of major kidney deterioration or kidney-related or cardiovascular death. This was not a kidney-only outcome, and the selected patient population and early stopping limit broader conclusions; it was not a test of longevity in healthy people. Population: 3533 adults with type 2 diabetes and CKD, 1767/1766; age/sex distribution not extracted from the abstract. Species: Homo sapiens Intervention and comparator: Semaglutide 1.0 mg subcutaneously weekly Comparator: Placebo Endpoint: Primary composite: kidney failure, at least 50% eGFR loss, or kidney/CV death Reported result: 331 versus 410 events; HR 0.76 (95% CI 0.66–0.88), P=0.0003. Follow-up: Median 3.4 years

Among the same adults with type 2 diabetes and chronic kidney disease in FLOW, deaths from any cause were less frequent with semaglutide than with placebo. This result was part of the trial’s planned sequence of statistical tests. It adds an outcome from the same trial, not independent confirmation or evidence of longer life in healthy people. Population: 3533 adults with type 2 diabetes and CKD, 1767/1766; age/sex distribution not extracted from the abstract. Species: Homo sapiens Intervention and comparator: Semaglutide 1.0 mg subcutaneously weekly Comparator: Placebo Endpoint: Hierarchically tested secondary all-cause death; eGFR slope/MACE precede it Reported result: Death HR 0.80 (0.67–0.95), P=0.01; MACE HR 0.82 (0.68–0.98). Follow-up: Median 3.4 years

In STEP-HFpEF, semaglutide was compared with placebo in adults who had obesity and heart failure with preserved ejection fraction, without diabetes. It improved heart-failure symptoms and physical limitations and reduced weight. These findings do not establish a reduction in deaths, and they apply to this specific heart-failure population and treatment regimen. Population: 529 adults with obesity-related HFpEF without diabetes; age/sex distribution not extracted. Species: Homo sapiens Intervention and comparator: Semaglutide 2.4 mg weekly Comparator: Placebo Endpoint: Dual primary KCCQ clinical summary score and weight; secondary 6-minute walk Reported result: KCCQ difference +7.8 points (4.8–10.9); weight −10.7 percentage points (−11.9 to −9.4); walk +20.3 m (8.6–32.1). Follow-up: 52 weeks

In a separate STEP-HFpEF trial, adults with obesity, type 2 diabetes and heart failure with preserved ejection fraction had better symptom and physical-limitation scores and greater weight loss with semaglutide than with placebo. These results do not prove a survival benefit. Combining this trial with the earlier trial without diabetes reuses both groups of participants; it does not create a third independent trial or a randomized comparison of diabetes status. Population: 616 adults with obesity-related HFpEF and type 2 diabetes in the DM trial; pooled report adds the separate 529-person non-diabetes trial. Age/sex distribution not extracted. Species: Homo sapiens Intervention and comparator: Semaglutide 2.4 mg weekly Comparator: Placebo Endpoint: Dual primary KCCQ and weight; confirmatory secondary walking Reported result: 616 randomized: KCCQ +7.3 points (4.1–10.4), weight −6.4 percentage points (−7.6 to −5.2); walk +14.3 m (3.7–24.9). Pooled N=1145 is 529+616. Follow-up: 52 weeks