Effect of semaglutide on kidney outcomes in the SELECT, FLOW, and SOUL trials: a prespecified pooled analysis

Semaglutide reduced the risk of major kidney outcomes compared with placebo across 30 787 participants pooled from three randomised trials of people with chronic kidney disease or atherosclerotic cardiovascular disease. The primary kidney-composite outcome was lower with semaglutide (HR 0.84, 95% CI 0.77-0.91), and safety was broadly similar, with serious adverse events numerically lower.

Journal article — Pooled participant-level analysis of three RCTs. Population: Adults with chronic kidney disease (FLOW) or atherosclerotic cardiovascular disease (SELECT and SOUL), with or without diabetes, on standard of care.. Sample size: 30 787 participants. Follow-up: Mean follow-up 39.5-47.5 months across trials. Interventions: Semaglutide 1.0 mg once-weekly subcutaneous (FLOW); Semaglutide 2.4 mg once-weekly subcutaneous (SELECT); Semaglutide 14 mg once-daily oral (SOUL).

Across 30 787 pooled participants, first events of the primary kidney composite occurred in 973 participants assigned to semaglutide versus 1134 assigned to placebo, giving a hazard ratio of 0.84 (95% CI 0.77-0.91). First events of the narrower secondary kidney composite excluding cardiovascular-related death occurred in 347 versus 416 participants, giving a hazard ratio of 0.80 (95% CI 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 numerically lower with semaglutide than with placebo.

For researchers studying semaglutide, this paper pools participant-level data from three phase 3 trials to show reduced major kidney outcomes across a broad cardio-kidney-metabolic population, with or without diabetes. It does not establish the mechanism of benefit, nor does it provide head-to-head comparisons of the different semaglutide doses or routes.

Key findings

• The primary kidney composite occurred in 973 semaglutide-assigned participants versus 1134 placebo-assigned participants (HR 0.84, 95% CI 0.77-0.91).
• The narrower secondary kidney composite excluding cardiovascular-related death occurred in 347 versus 416 participants (HR 0.80, 95% CI 0.69-0.92).
• Mean follow-up across the trials was 39.5-47.5 months.
• Serious adverse events were numerically lower with semaglutide than with placebo, and safety was otherwise generally similar between groups.

Limitations

• The three trials differed in participants' baseline characteristics.
• Semaglutide was given at different doses and routes of administration across trials.
• The pooled analysis does not establish whether the benefit is explained by glycaemic or weight-management effects.
• It cannot directly compare the relative effects of the different semaglutide doses or routes.

The record

• Journal: The lancet. Diabetes & endocrinology: S2213-8587(26)00134-8
• Published: 2026-08-07
• PMID: 42567173 — DOI: 10.1016/s2213-8587(26)00134-8
• Author countries: Australia, Denmark, Germany, UK, USA

Peptide profiles: Semaglutide.

All indexed evidence: Semaglutide trials & papers.

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