Pooled participant-level analysis of three randomized placebo-controlled trials (SELECT, FLOW, SOUL; N=30,787) evaluating semaglutide (subcutaneous 1.0 mg weekly, subcutaneous 2.4 mg weekly, or oral 14 mg daily) versus placebo added to standard of care in adults with CKD or atherosclerotic cardiovascular disease, over a mean follow-up of 39.5–47.5 months.
Semaglutide reduced the primary kidney composite (≥50% eGFR decline, kidney failure, kidney-related death, or CV death) vs. placebo: 973 vs. 1,134 first events (HR 0.84, 95% CI 0.77–0.91). The narrower kidney-only composite also favored semaglutide: 347 vs. 416 events (HR 0.80, 95% CI 0.69–0.92). Serious adverse events were numerically lower with semaglutide.
- Three different doses and routes of administration were pooled, limiting direct comparability across formulations. - Baseline characteristics differed across trials (e.g., diabetes prevalence, CKD severity), which may introduce heterogeneity. - Funded by Novo Nordisk, introducing potential industry bias.
Across a broad cardio-kidney-metabolic population—with or without diabetes—semaglutide (oral or injectable) meaningfully reduces major kidney and cardiovascular outcomes with a favorable safety profile. Clinicians should consider semaglutide for kidney protection beyond its glucose-lowering or weight-loss effects alone.
