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Mann, J.F.E.* ; Marx, N.* ; Deanfield, J.E.* ; Emerson, S.S.* ; Inzucchi, S.E.* ; McGuire, D.K.* ; Mulvagh, S.L.* ; Pop-Busui, R.* ; Poulter, N.R.* ; Engelmann, M.D.M.* ; Hovingh, G.K.* ; Belmar, N.* ; Idorn, T.* ; Jeppesen, O.K.* ; Birkenfeld, A.L. ; Amod, A.* ; Mankovsky, B.* ; Desouza, C.* ; Gorgojo-Martinez, J.J.* ; Arechavaleta, R.* ; Tu, S.T.* ; Buse, J.B.*

Impact of oral semaglutide on kidney outcomes in people with type 2 diabetes: Results from the SOUL randomized trial.

Diabetes Care, DOI: 10.2337/dc25-1080 (2025)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
OBJECTIVE: To examine the effects of oral semaglutide on kidney outcomes in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: SOUL (NCT03914326), a double-blind randomized controlled trial, compared oral semaglutide with placebo in people with T2D, ASCVD, and/or CKD, showing a 14% reduction in risk of major adverse cardiovascular (CV) events. Prespecified kidney outcomes included a five-point composite (≥50% decrease in estimated glomerular filtration rate [eGFR], persistent eGFR <15 mL/min/1.73 m2, initiation of chronic kidney replacement therapy, or death from kidney or CV causes); a four-point composite (excluding CV death); and eGFR decline. Prespecified subgroups were also assessed, including those with eGFR <60 mL/min/1.73 m2 at baseline. RESULTS: Among 9,650 participants, mean eGFR was 73.8 mL/min/1.73 m2, and follow-up was 47.5 months. The five-point outcome occurred in 403 (8.4%) and 435 (9.0%) participants taking oral semaglutide versus placebo, respectively (hazard ratio [HR] 0.91; 95% CI 0.80, 1.05; P = 0.19). The four-point outcome occurred in 112 (2.3%) and 129 (2.7%) participants, respectively (HR 0.86; 95% CI 0.66, 1.10; P = 0.22). Mean annual eGFR decline was less with oral semaglutide than placebo (-1.67 vs. -2.06 mL/min/1.73 m2; estimated treatment difference 0.40 [95% CI 0.27, 0.53; P < 0.0001). These effects were similar across most subgroups, including those with eGFR <60 mL/min/1.73 m2. Serious adverse events occurred at similar rates in both groups. CONCLUSIONS: In people with T2D and ASCVD and/or CKD but with overall mostly preserved eGFR, orally administered semaglutide, compared with placebo, did not significantly reduce adverse kidney outcomes but did slow the decline in eGFR.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0149-5992
e-ISSN 1935-5548
Journal Diabetes Care
Publisher American Diabetes Association
Publishing Place Alexandria, Va.
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)