Effect of semaglutide on kidney outcomes in the SELECT, FLOW, and SOUL trials: a prespecified pooled analysis
In brief
Semaglutide lowers risk of major kidney events by about 16% in cardio-kidney patients
In a pooled analysis of 30,787 participants from three phase-3 trials, weekly or daily semaglutide reduced the composite of 50% eGFR decline, kidney failure, kidney-related death or cardiovascular death by 16% compared with placebo over roughly three to four years. Safety was comparable to other GLP-1 agents, suggesting a broad cardio-renal benefit that extends beyond glucose control, though differences in dose and patient mix warrant further study.
- Journal
- The lancet. Diabetes & endocrinology (Q1)
- Published
- 7 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Johannes F E Mann, Sunil V Badve, Florian M M Baeres, Nicolas Belmar, Kirstine Brown-Frandsen, John B Buse, et al.
- PMID
- 42567173
- DOI
- 10.1016/S2213-8587(26)00134-8
Why clinicians should know about it
- Picked for Endocrinology, Diabetes and Metabolism (top studies of the week, 9 August 2026).
- Picked for Internal Medicine (top studies of the week, 9 August 2026): Pooled analysis of semaglutide on kidney outcomes
- Picked for Nephrology (top studies of the week, 9 August 2026): Semaglutide reduces major kidney outcomes across CKD trials
Abstract
BACKGROUND: The GLP-1 receptor agonist semaglutide reduces clinically important kidney outcomes in people with type 2 diabetes and chronic kidney disease (CKD). We aimed to assess the pooled effects of semaglutide on kidney outcomes in prespecified analyses of participant-level data from the diverse populations of the SELECT, FLOW, and SOUL randomised placebo-controlled trials. METHODS: Participants with CKD (FLOW) or atherosclerotic cardiovascular disease (SELECT and SOUL) were randomly assigned semaglutide (once-weekly subcutaneous 1·0 mg [FLOW], once-weekly subcutaneous 2·4 mg [SELECT], or once-daily oral 14 mg [SOUL]) or matching placebo, added to standard of care. The primary outcome in this pooled analysis was time to first occurrence of a kidney composite, defined as onset of persistent 50% or greater reduction in estimated glomerular filtration rate (eGFR), kidney failure (persistent eGFR <15 mL/min per 1·73 m2, or initiation of kidney replacement therapy), kidney-related death, or cardiovascular-related death. Safety was also assessed. FINDINGS: The pooled participants from the trials (N=30 787) had a mean follow-up of 39·5-47·5 months. Among participants assigned to semaglutide, 973 first events of the primary kidney composite occurred compared with 1134 first events for placebo (hazard ratio [HR] 0·84 [95% CI 0·77-0·91]). First events of a narrower secondary kidney composite (excluding cardiovascular-related death from the primary outcome) were also reduced with semaglutide versus placebo (347 and 416, respectively; 0·80 [0·69-0·92]). Safety outcomes were overall similar between groups, and in line with other GLP-1 receptor agonist trials. Serious adverse events were numberically lower with semaglutide than with placebo. INTERPRETATION: Data pooled from three large phase 3 trials suggest that semaglutide reduces the risk of major kidney outcomes in a broad population with cardio-kidney-metabolic disease while having a favourable risk-benefit profile. In people with cardio-kidney-metabolic disease, with and without diabetes, semaglutide (oral or injected) prevents kidney-related and cardiovascular complications and induces adverse events in line with GLP-1 receptor agonist studies, regardless of baseline characteristics within the cardio-kidney-metabolic spectrum. This was a participant-level analysis conducted in a large database of three randomised controlled trials of similar design and examining the same treatment, but there were some differences in participants' baseline characteristics, and in the dose and route of administration of treatment. This pooled analysis adds evidence for the benefit of GLP-1 receptor agonists in general, and semaglutide in particular, in a broad population of people with cardio-kidney-metabolic disease, suggesting that the benefit of semaglutide might not be explained only by its glycaemic effects, weight-management effects, or both. FUNDING: Novo Nordisk.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.