Pooled Analysis of Three Phase 3 Trials in The Lancet Diabetes & Endocrinology Finds Semaglutide Cut Major Kidney Events by 16%

The Lancet Diabetes & Endocrinology published a prespecified pooled analysis on August 7, 2026, examining whether semaglutide's kidney benefits, previously documented mainly in people with diabetes, extend across a broader population with cardio-kidney-metabolic disease. The analysis was led by Johannes F.E. Mann of the KfH Kidney Center in Munich and Vlado Perkovic of the University of New South Wales, with co-authors from Novo Nordisk and multiple academic centers involved in the underlying trials.

The authors combined participant-level data from three completed randomized, placebo-controlled phase 3 trials of semaglutide: FLOW, which enrolled people with type 2 diabetes and chronic kidney disease and used once-weekly subcutaneous semaglutide 1.0 mg; SELECT, which enrolled people with overweight or obesity and established atherosclerotic cardiovascular disease but not diabetes, using once-weekly subcutaneous semaglutide 2.4 mg; and SOUL, which enrolled people with type 2 diabetes and atherosclerotic cardiovascular disease using once-daily oral semaglutide 14 mg. Across the three trials, 30,787 participants were followed for a mean of 39.5 to 47.5 months.

The prespecified primary outcome for the pooled analysis was time to first occurrence of a kidney composite: sustained 50% or greater reduction in estimated glomerular filtration rate (eGFR), kidney failure (sustained eGFR below 15 mL/min per 1.73 square meters or initiation of kidney replacement therapy), kidney-related death, or cardiovascular-related death. This composite occurred as a first event in 973 participants assigned to semaglutide compared with 1,134 assigned to placebo, a hazard ratio of 0.84 (95% CI 0.77-0.91).

A narrower secondary kidney composite that excluded cardiovascular-related death, isolating outcomes more specific to the kidney, was also reduced with semaglutide: 347 first events versus 416 with placebo, a hazard ratio of 0.80 (95% CI 0.69-0.92). The authors report that safety outcomes were broadly similar between the semaglutide and placebo groups and consistent with findings from other GLP-1 receptor agonist trials, with serious adverse events numerically lower among participants who received semaglutide.

The authors note the analysis pools three trials of similar design testing the same drug across different doses, formulations, and routes of administration (subcutaneous weekly, subcutaneous weekly at a higher dose, and oral daily) in populations with differing baseline characteristics, rather than constituting a new randomized trial in its own right. They conclude the findings suggest semaglutide's kidney and cardiovascular benefits are not fully explained by its glycemic or weight-management effects alone, and that the drug reduces major kidney outcomes across a broad population spanning the cardio-kidney-metabolic spectrum, with and without diabetes.

The study was funded by Novo Nordisk, which manufactures semaglutide and markets it as Ozempic and Rybelsus for type 2 diabetes and Wegovy for chronic weight management. Semaglutide is already approved by the FDA, the European Medicines Agency, and Australia's Therapeutic Goods Administration. This pooled analysis does not change that regulatory status, and nothing in it constitutes treatment or dosing guidance; kidney and cardiovascular risk should be assessed by a qualified clinician.