81-OR: Once-Weekly Semaglutide 2.4 mg Improved Glucose Metabolism and Prediabetes in Adults with Overweight/Obesity in the STEP 1 Trial

Abstract

Semaglutide 2.4 mg demonstrated 14.9% body weight (BW) loss in adults with overweight/obesity in STEP 1. We evaluated effects on glucose metabolism in subjects with prediabetes at baseline (BL). Subjects (N=1961) were randomized 2:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo (PBO), plus lifestyle intervention, for 68 wks. Post-hoc analyses included change from BL to wk 68 in glycemic status (normoglycemia, prediabetes, or type 2 diabetes; all investigator assessed), HbA1c, fasting plasma glucose (FPG), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Statistical analyses were not adjusted for multiplicity. At BL, 856 (43.7%) subjects had prediabetes (593 semaglutide/263 PBO; mean HbA1c: 5.9/5.9%, FPG: 98.7/97.6 mg/dL, HOMA-IR: 4.2/4.1, BW: 106.9/106.9 kg). By wk 68, 84.1% of those with prediabetes at BL were normoglycemic with semaglutide vs. 47.8% with PBO (p<0.0001) (Figure); of those who reverted from prediabetes to normoglycemia in the semaglutide group, the majority achieved weight loss ≥10%. Treatment with semaglutide vs. PBO lowered HbA1c (difference: -0.35 percentage‑points; p<0.0001), FPG (-8.49 mg/dL; p<0.0001) and HOMA-IR (relative % change: -28%; p<0.0001).In conclusion, once weekly semaglutide 2.4 mg allowed most adults with overweight/obesity and prediabetes to revert to normoglycemia at wk 68.View largeDownload slideView largeDownload slide DisclosureL. Perreault: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk, Consultant; Self; Sanofi, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk. C. Le roux: Advisory Panel; Self; Boehringer Ingelheim International GmbH, GI Dynamics, Herbalife International of America, Inc., Johnson & Johnson, Medtronic, Novo Nordisk A/S. M. J. Davies: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Boehringer Ingelheim Limited (UK), Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi, Other Relationship; Self; AstraZeneca, NIHR Leicester Biomedical Research Centre, Novo Nordisk, Speaker’s Bureau; Self; Astra Zeneca Pharma India Ltd, Boehringer Ingelheim (China), Boehringer Ingelheim (Philippines), Inc., Boehringer Ingelheim International GmbH, Boehringer Ingelheim Limited (UK), Boehringer Ingelheim Saudi Arabia Trading, Boehringer Ingelheim Singapore Pte. Ltd, Boehringer Ingelheim Sp. Z o. o., Eli Lilly and Company, Napp Pharmaceuticals, Novo Nordisk, Novo Nordisk A/S, S. C. Sanofi Romania SRL, Sanofi K. K. J. P. Frias: Consultant; Self; 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, CymaBay Therapeutics, Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Speaker’s Bureau; Self; Merck & Co., Inc., Sanofi. P. N. Laursen: Employee; Self; Novo Nordisk A/S. I. Lingvay: Advisory Panel; Self; Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Consultant; Self; TARGET PharmaSolutions, Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Zealand Pharma A/S, Research Support; Self; Mylan N. V., Sanofi. S. Machineni: Consultant; Self; Novo Nordisk, Rhythm Pharmaceuticals, Inc., Other Relationship; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk. A. Varbo: Employee; Self; Novo Nordisk A/S. J. Wilding: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Mundipharma International, Napp Pharmaceuticals, Novo Nordisk, Rhythm Pharmaceuticals, Inc., Saniona, Sanofi, Research Support; Self; AstraZeneca, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Napp Pharmaceuticals. S. O. R. Wallenstein: Employee; Self; Novo Nordisk.FundingNovo Nordisk A/S