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Publications

Journal Article Randomized Controlled Trial Ppublish

PubMed: 41380027 DOI: 10.2337/dc25-1080

Impact of Oral Semaglutide on Kidney Outcomes in People With Type 2 Diabetes: Results From the SOUL Randomized Trial.

Diabetes Care 49(2):257-265

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

Affiliations

  • KfH Kidney Center, Munich, Germany.
  • Friedrich Alexander University, Erlangen, Germany.
  • RWTH Aachen University, University Hospital Aachen, Aachen, Germany.
  • Institute of Cardiovascular Sciences, University College London, London, U.K.
  • Department of Biostatistics, University of Washington, Seattle, WA.
  • Section of Endocrinology, Yale University School of Medicine, New Haven, CT.
  • Clinic for Cardiology, Angiology, and Intensive Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
  • Parkland Health and Hospital System, Dallas, TX.
  • Division of Cardiology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
  • Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon Health and Science University, Portland, OR.
  • Imperial Clinical Trials Unit, Imperial College London, London, U.K.
  • Novo Nordisk A/S, Søborg, Denmark.
  • Department of Diabetology, Endocrinology and Nephrology, University Hospital Tübingen, Tübingen, Germany.
  • German Center for Diabetes Research and Institute for Diabetes Research and Metabolic Diseases, Helmholtz Munich, Germany.
  • Life Chatsmed Garden Hospital and University of KwaZulu-Natal, Durban, South Africa.
  • Institute of Gerontology, Kyiv, Ukraine.
  • Division of Diabetes, Endocrinology, and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE.
  • Department of Endocrinology and Nutrition, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
  • Department of Endocrinology, Universidad Autonoma de Guadalajara, Jalisco, Mexico.
  • Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.
  • University of North Carolina School of Medicine, Chapel Hill, NC.

Abstract

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.

MeSH

Diabetes Mellitus, Kidney, Therapeutics, Diabetes Mellitus, Type 2, Semaglutide