Leigh Perreault1, Melanie Davies2, Juan P Frias3, Peter Nørkjaer Laursen4, Ildiko Lingvay5, Sriram Machineni6, Anette Varbo4, John P H Wilding7, Signe Olrik Rytter Wallenstein4, Carel W le Roux8. 1. Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO. 2. Diabetes Research Centre, University of Leicester; and NIHR Leicester Biomedical Research Centre, Leicester, U.K. 3. National Research Institute, Los Angeles, CA. 4. Novo Nordisk A/S, Søborg, Denmark. 5. Department of Internal Medicine/Endocrinology and Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX. 6. Division of Endocrinology and Metabolism, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC. 7. Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, U.K. 8. Diabetes Complications Research Centre, Conway Institute, University College, Dublin, Ireland.
Abstract
OBJECTIVE: This analysis of 3,375 adults with overweight/obesity across the Semaglutide Treatment Effect in People with obesity (STEP) 1, 3, and 4 trials evaluated whether more participants with prediabetes had normoglycemia after 68 weeks' treatment with once-weekly semaglutide 2.4 mg plus lifestyle intervention versus placebo and assessed changes in glucose metabolism in participants with prediabetes. RESEARCH DESIGN AND METHODS: STEP 1, 3, and 4 were phase 3, 68-week, randomized, placebo-controlled, multinational trials; STEP 4 had a 20-week semaglutide run-in and 48-week randomized period. Analyses included changes (week 0-68; before the washout period) in glycemic status (prespecified: STEP 1 and 3; post hoc: STEP 4), and in HbA1c, fasting plasma glucose (FPG), and HOMA insulin resistance (HOMA-IR) among participants with prediabetes (post hoc). RESULTS: Significantly more participants with baseline (week 0) prediabetes (n = 1,536) had normoglycemia at week 68 with semaglutide versus placebo (STEP 1, 84.1% vs. 47.8%; STEP 3, 89.5% vs. 55.0%; STEP 4, 89.8% vs. 70.4%; all P < 0.0001). Fewer participants with baseline normoglycemia had prediabetes at week 68 with semaglutide versus placebo (STEP 1, 2.9% vs. 10.9%; STEP 3, 3.2% vs. 5.8%; STEP 4, 1.1% vs. 5.0%). Semaglutide resulted in greater improvements in HbA1c, FPG, and HOMA-IR than placebo among participants with baseline prediabetes (all P < 0.01). CONCLUSIONS: STEP 1, 3, and 4 collectively provide a robust assessment of the effects of semaglutide on glucose metabolism and prediabetes in a large cohort of adults with overweight/obesity while on treatment. Among participants with baseline prediabetes, 68 weeks' treatment with semaglutide versus placebo led to significant improvements in glucose metabolism and a higher likelihood of normoglycemia.
OBJECTIVE: This analysis of 3,375 adults with overweight/obesity across the Semaglutide Treatment Effect in People with obesity (STEP) 1, 3, and 4 trials evaluated whether more participants with prediabetes had normoglycemia after 68 weeks' treatment with once-weekly semaglutide 2.4 mg plus lifestyle intervention versus placebo and assessed changes in glucose metabolism in participants with prediabetes. RESEARCH DESIGN AND METHODS: STEP 1, 3, and 4 were phase 3, 68-week, randomized, placebo-controlled, multinational trials; STEP 4 had a 20-week semaglutide run-in and 48-week randomized period. Analyses included changes (week 0-68; before the washout period) in glycemic status (prespecified: STEP 1 and 3; post hoc: STEP 4), and in HbA1c, fasting plasma glucose (FPG), and HOMA insulin resistance (HOMA-IR) among participants with prediabetes (post hoc). RESULTS: Significantly more participants with baseline (week 0) prediabetes (n = 1,536) had normoglycemia at week 68 with semaglutide versus placebo (STEP 1, 84.1% vs. 47.8%; STEP 3, 89.5% vs. 55.0%; STEP 4, 89.8% vs. 70.4%; all P < 0.0001). Fewer participants with baseline normoglycemia had prediabetes at week 68 with semaglutide versus placebo (STEP 1, 2.9% vs. 10.9%; STEP 3, 3.2% vs. 5.8%; STEP 4, 1.1% vs. 5.0%). Semaglutide resulted in greater improvements in HbA1c, FPG, and HOMA-IR than placebo among participants with baseline prediabetes (all P < 0.01). CONCLUSIONS: STEP 1, 3, and 4 collectively provide a robust assessment of the effects of semaglutide on glucose metabolism and prediabetes in a large cohort of adults with overweight/obesity while on treatment. Among participants with baseline prediabetes, 68 weeks' treatment with semaglutide versus placebo led to significant improvements in glucose metabolism and a higher likelihood of normoglycemia.
Authors: W Timothy Garvey; Rachel L Batterham; Meena Bhatta; Silvio Buscemi; Louise N Christensen; Juan P Frias; Esteban Jódar; Kristian Kandler; Georgia Rigas; Thomas A Wadden; Sean Wharton Journal: Nat Med Date: 2022-10-10 Impact factor: 87.241