Visual Abstract
This analysis evaluated the effect of semaglutide 2.4 mg vs. placebo (PBO) or semaglutide 1.0 mg on cardiometabolic risk in STEP 2, a double-blind, placebo-controlled trial in which 1210 adults with overweight/obesity and type 2 diabetes (T2D) were randomized 1:1:1 to 68 weeks’ once-weekly semaglutide 2.4 mg, 1.0 mg, or PBO, plus lifestyle intervention. Primary endpoints included percent change in body weight (BW). Secondary endpoints included change in cardiometabolic risk factors (including post-hoc analyses of non-high density lipoprotein cholesterol). Mean BW change from baseline to week 68 was −9.6% with semaglutide 2.4 mg vs. −3.4% with PBO (estimated treatment difference [ETD]: −6.2%; 95% CI: −7.3, −5.2; p<0.0001) and -7.0% with semaglutide 1.0 mg (ETD: −2.7%; 95% CI: −3.7, −1.6; p<0.0001). Semaglutide 2.4 mg improved other cardiometabolic parameters vs. PBO (Table): HbA1c, waist circumference, systolic blood pressure, levels of triglycerides, C-reactive protein, fasting plasma glucose, and fasting insulin (p<0.01 for all ETDs/estimated treatment ratios). Improvements were similar with semaglutide 1.0 mg except for change in BW and waist circumference. Overall, in adults with overweight/obesity and T2D, semaglutide 2.4 mg improved cardiometabolic risk vs. PBO, indicating favorable effects of semaglutide 2.4 mg beyond BW loss.
R. F. Kushner: Advisory Panel; Self; Novo Nordisk A/S. S. Verma: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Sanofi, Research Support; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, EOCI Pharmacomm Ltd., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Sanofi, Sun Pharmaceutical Industries Ltd., Toronto Knowledge Translation Working Group. 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. Deanfield: None. W. Garvey: None. O. Jeppesen: Employee; Self; Novo Nordisk A/S, Employee; Spouse/Partner; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S, Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. U. Khalid: None. M. N. Kosiborod: Consultant; Self; Amgen Inc., Applied Therapeutics, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk, Sanofi, Vifor Pharma Management Ltd., Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH. P. N. Laursen: Employee; Self; Novo Nordisk A/S. D. Rubino: Advisory Panel; Self; Novo Nordisk, Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk, Speaker’s Bureau; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk.
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