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DC24-0491.R2 Kahn et al SELECT Glycemic Status by Weight Loss Online-only Supplemental Material Final 041724 SK .pdf (498.08 kB)

EFFECT OF SEMAGLUTIDE ON REGRESSION AND PROGRESSION OF GLYCEMIA IN PEOPLE WITH OVERWEIGHT OR OBESITY BUT WITHOUT DIABETES IN THE SELECT TRIAL

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posted on 2024-06-22, 00:10 authored by 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

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 ≥45 years, body mass index ≥27 kg/m2, 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. On both treatment arms, mean nadir HbA1c was at 20 weeks. Thereafter, it increased similarly in both arms with a mean difference of -0.32% (95% CI: -0.33% to -0.30%; -3.49 mmol/mol [-3.66; -3.32]) 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 NNT 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.

Funding

The SELECT Trial was supported by Novo Nordisk A/S.

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