1413-P: Semaglutide 2.4 mg Improved Glucose Metabolism and Reverted Prediabetes to Normoglycemia in Adults with Overweight/Obesity vs. Liraglutide 3.0 mg (STEP 8)

The STEP 8 trial randomized 338 adults with overweight/obesity to weekly semaglutide 2.4 mg or placebo (PBO) , or daily liraglutide 3.0 mg or PBO, plus lifestyle intervention for 68 wks (3:1:3:1) ; PBO data not shown. Body weight (BW) change was greater with semaglutide vs. liraglutide (-15.8% vs. -6.4%, respectively; p<0.0001) . This exploratory analysis assessed effects on glucose metabolism and glycemic status (normoglycemia; prediabetes; T2D) at wk 68 in participants (pts) with prediabetes at baseline (BL; 43 semaglutide/45 liraglutide; mean HbA1c 5.9/5.8%; fasting plasma glucose [FPG] 102/100 mg/dL; HOMA-IR 4.9/3.7; BW 104/1kg) . Analyses were not adjusted for multiplicity. At wk 68, 89.5% of pts were normoglycemic with semaglutide vs. 64.9% with liraglutide (p=0.01) (Figure) ; in these pts, 76.5% had weight loss ≥10% with semaglutide vs. 33.3% with liraglutide. One pt in each group developed T2D (Figure) . From BL to wk 68, semaglutide led to greater reductions vs. liraglutide in HbA1c (difference: -0.22 %; p=0.0002) , FPG (difference: -6.2 mg/dL; p=0.02) , and HOMA-IR (relative % difference: -28%; p=0.02) . In conclusion, both semaglutide 2.4 mg and liraglutide 3.0 mg had clinically beneficial effects on glucose metabolism and glycemic status in pts with overweight/obesity and prediabetes, though the effect of semaglutide was greater vs. liraglutide. Disclosure J.Rosenstock: Consultant; AstraZeneca, Other Relationship; Applied Therapeutics, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Research Support; Genentech, Inc., Merck & Co., Inc., Metacrine, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., vTv Therapeutics. W.Garvey: Other Relationship; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Epitomee, JAZZ Pharmaceuticals, Novo Nordisk, Novo Nordisk, Pfizer Inc., Pfizer Inc. B.Goldman: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. U.Khalid: None. R.Sørrig: Employee; Novo Nordisk A/S. D.Rubino: Advisory Panel; Novo Nordisk, Other Relationship; Endocrine Society, PeerView, WebMD LLC, Research Support; Boehringer Ingelheim International GmbH, Novo Nordisk, Obesinov, SARL, Speaker's Bureau; Novo Nordisk, Stock/Shareholder; Novo Nordisk. Funding Funded by Novo Nordisk A/S