Effect of Semaglutide on Regression and Progression of Glycemia in People With Overweight or Obesity but Without Diabetes in the SELECT Trial

Authors

• Steven E. Kahn, University of Washington, Seattle, WA
• John E. Deanfield, University College London, London, U.K.
• Ole Kleist Jeppesen, Novo Nordisk A/S, Søborg, Denmark
• Scott S. Emerson, University of Washington, Seattle, WA
• Trine Welløv Boesgaard, Novo Nordisk A/S, Søborg, Denmark
• Helen M. Colhoun, University of Edinburgh, Edinburgh, U.K.
• Robert F. Kushner, Northwestern University Feinberg School of Medicine, Chicago, IL
• Ildiko Lingvay, University of Texas Southwestern Medical Center, Dallas, TX
• Bartolome Burguera, Cleveland Clinic, Cleveland, OH
• Grzegorz Gajos, Jagiellonian University Medical College, Kraków, Poland
• Deborah Bade Horn, University of Texas, Houston, TX
• Irene M. Hramiak, Western University, London, Ontario, Canada
• Ania M. Jastreboff, Yale School of Medicine, New Haven, CT
• Alexander Kokkinos, National and Kapodistrian University of Athens, Athens, Greece
• Michael Maeng, Aarhus University, Aarhus, Denmark
• Ana Laura S A Matos, Novo Nordisk A/S, Søborg, Denmark
• Francisco J. Tinahones, Malaga University, Málaga, Spain
• A Michael Lincoff, Case Western Reserve University, Cleveland, OH
• Donna H. Ryan, Pennington Biomedical Research Center, Baton Rouge, LA
• SELECT Trial Investigators

Document Type

Article

Publication Date

8-1-2024

Publication Title

Diabetes Care: The Journal of Clinical and Applied Research and Education

Abstract

Objective: To determine whether semaglutide slows progression of glycemia in people with cardiovascular disease and overweight or obesity but without diabetes. Research design and methods: In a multicenter, double-blind trial, participants aged ≥45 years, with BMI ≥27 kg/m2, and with preexisting cardiovascular disease but without diabetes (HbA1c < 6.5%) were randomized to receive subcutaneous semaglutide (2.4 mg weekly) or placebo. Major glycemic outcomes were HbA1c and proportions achieving biochemical normoglycemia (HbA1c < 5.7%) and progressing to biochemical diabetes (HbA1c ≥6.5%). Results: Of 17,604 participants, 8,803 were assigned to semaglutide and 8,801 to placebo. Mean ± SD intervention exposure was 152 ± 56 weeks and follow-up 176 ± 40 weeks. In both treatment arms mean nadir HbA1c for participants was at 20 weeks. Thereafter, HbA1c increased similarly in both arms, with a mean difference of -0.32 percentage points (95% CI -0.33 to -0.30; -3.49 mmol/mol [-3.66 to -3.32]) and with the difference favoring semaglutide throughout the study (P < 0.0001). Body weight plateaued at 65 weeks and was 8.9% lower with semaglutide. At week 156, a greater proportion treated with semaglutide were normoglycemic (69.5% vs. 35.8%; P < 0.0001) and a smaller proportion had biochemical diabetes by week 156 (1.5% vs. 6.9%; P < 0.0001). The number needed to treat was 18.5 to prevent a case of diabetes. Both regression and progression were dependent on glycemia at baseline, with the magnitude of weight reduction important in mediating 24.5% of progression and 27.1% of regression. Conclusions: In people with preexisting cardiovascular disease and overweight or obesity but without diabetes, long-term semaglutide increases regression to biochemical normoglycemia and reduces progression to biochemical diabetes but does not slow glycemic progression over time.

First Page

1350

Last Page

1359

DOI

10.2337/dc24-0491

Rights

© 2025 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered

Recommended Citation

Kahn, Steven E.; Deanfield, John E.; Jeppesen, Ole Kleist; Emerson, Scott S.; Boesgaard, Trine Welløv; Colhoun, Helen M.; Kushner, Robert F.; Lingvay, Ildiko; Burguera, Bartolome; Gajos, Grzegorz; Horn, Deborah Bade; Hramiak, Irene M.; Jastreboff, Ania M.; Kokkinos, Alexander; Maeng, Michael; Matos, Ana Laura S A; Tinahones, Francisco J.; Lincoff, A Michael; Ryan, Donna H.; and Investigators, SELECT Trial, "Effect of Semaglutide on Regression and Progression of Glycemia in People With Overweight or Obesity but Without Diabetes in the SELECT Trial" (2024). LSU-LCMC Cancer Center Faculty Publications. 98.
https://digitalscholar.lsuhsc.edu/llcc_facpubs/98
10.2337/dc24-0491