2-LB: Semaglutide 2.4 mg Reduces the 10-Year T2D Risk in People with Overweight/Obesity

Abstract

The effect of once-weekly s.c. semaglutide 2.4 mg (sema) on the risk of developing T2D in people with obesity is unknown. Weight management with sema vs. PBO plus diet/exercise was assessed in participants (pts) with overweight/obesity in STEP 1 (68 wks) and STEP 4 (20-wk run-in on sema, 48-wk randomized withdrawal) . The 10-yr T2D risk was calculated post hoc using Cardiometabolic Disease Staging (CMDS) , a validated Bayesian logistic regression of T2D risk factors. Risk scores decreased after 68 wks from 18% to 7% with sema, and 18% to 16% with PBO (61% vs. 13% reduction [p<0.01]; STEP 1; Figure) . Most of the risk score reduction with sema occurred during wks 0-20, from 21% to 11%; risk score decreased further to 8% with continued sema during wks 20-68, but increased to 15% with switch to PBO (32% reduction vs. 41% increase [p<0.01]; STEP 4; Figure) . Wk 0 risk scores were higher in pts with prediabetes vs. normoglycemia (Figure) , but treatment effects were comparable at wk 68 (p=0.45 for interaction [STEP 1]) . Risk score changes mirrored weight loss, which was 17% with sema vs. 3% with PBO in STEP 1, and in STEP 4 was ‍11% for wks 0-20 with sema, and a further 9% with continued sema vs. a 6% regain with switch to PBO for wks 20-68. In summary, treatment with sema reduces the 10-yr risk of T2D by ∼60% regardless of initial glycemic status, with sustained treatment required to maintain this benefit. These data suggest sema could help prevent T2D in people with obesity. Disclosure W. Garvey: Other Relationship; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Epitomee, JAZZ Pharmaceuticals, Novo Nordisk, Novo Nordisk, Pfizer Inc., Pfizer Inc. T. Holst-hansen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. P. N. Laursen: Employee; Novo Nordisk A/S. A. R. Rinnov: Employee; Novo Nordisk. L. J. Wilkinson: Employee; Novo Nordisk. Funding Novo Nordisk A/S