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
John E Deanfield
Ole Kleist Jeppesen
Scott S Emerson
Trine Welløv Boesgaard
Helen M Colhoun
Robert F Kushner
Ildiko Lingvay
Bartolome Burguera
Grzegorz Gajos
Deborah Bade Horn
Irene M Hramiak
Ania M Jastreboff
Alexander Kokkinos
Michael Maeng
Ana Laura S A Matos
Francisco J Tinahones
A Michael Lincoff
Donna H Ryan
SELECT Trial Investigators

Publication Date

8-1-2024

Journal

Diabetes Care

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

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.

Keywords

Glucagon-Like Peptides, Humans, Male, Middle Aged, Female, Overweight, Obesity, Aged, Blood Glucose, Double-Blind Method, Glycated Hemoglobin, Hypoglycemic Agents

Comments

PMID: 38907683