Impact of Oral Semaglutide on Kidney Outcomes in People with Type 2 Diabetes: Results from the SOUL Randomized Trial
Year: 2025
Type: other
Abstract: OBJECTIVE To examine 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 randomized, double-blind trial, compared oral semaglutide vs placebo in people with T2D, ASCVD, and/or CKD, showing a 14% reduction in risk of major adverse CV events. Prespecified kidney outcomes included a 5-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 4-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 5-point outcome occurred in 403 (8.4%) and 435 (9.0%) on oral semaglutide vs placebo, respectively (HR 0.91; 95%CI 0.80-1.05; P=0.19). The 4-point outcome occurred in 112 (2.3%) and 129 (2.7%), respectively (HR 0.86 [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 [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 to placebo, did not significantly reduce adverse kidney outcomes but did slow the decline in eGFR.
Authors: Johannes F. E. Mann, Nikolaus Marx, John E. Deanfield, Scott S. Emerson, Silvio E. Inzucchi, Darren K. McGuire, Sharon L. Mulvagh, Rodica Pop-Busui, Neil R. Poulter, Mads D. M. Engelmann, G. Kees Hovingh, Nicolas Belmar, Thomas Idorn, Ole Kleist Jeppesen, Andreas L. Birkenfeld, Aslam Amod, Boris Mankovsky, Cyrus Desouza, Juan J. Gorgojo-Martinez, Rosario Arechavaleta, Shih-te Tu, John B. Buse
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4416994659