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The STEP 2 trial showed mean weight loss of 9.6% with semaglutide 2.4 mg vs. 7.0% with semaglutide 1.0 mg vs. 3.4% with placebo (PBO; both p<0.0001). We present detailed glucose metabolism outcomes. Adults with BMI ≥27 kg/m2, type 2 diabetes (T2D) and HbA1c 7-10% (53-86 mmol/mol) were randomized to 68 weeks’ once-weekly subcutaneous semaglutide 2.4 mg (N=404), 1.0 mg (N=403) or PBO (N=403). Glucose metabolism outcomes were secondary/exploratory endpoints. At baseline, patients had mean age 55 yrs, body weight 99.8 kg, HbA1c 8.1%, and diabetes duration 8.0 yrs; 88% were on 1-2 oral antihyperglycemic drugs (OAD). From weeks 0-68, semaglutide 2.4 mg and 1.0 mg reduced HbA1c to a greater extent vs. PBO (ETD: -1.2% [-13.5 mmol/mol] and -1.1% [-11.8 mmol/mol]; both p<0.0001), and improved FPG, HOMA-IR and -β, and reduced OAD use (Table). With semaglutide 2.4 mg, more patients achieved HbA1c <7.0% and ≤6.5%, and composite endpoints of HbA1c <7.0% with weight loss ≥10% or ≥15% vs. semaglutide 1.0 mg or PBO. To conclude, weight loss with semaglutide 2.4 mg was accomplished with improvements in insulin resistance and β-cell function, two key mechanistic drivers and pathophysiologic abnormalities that cause T2D and fuel diabetes progression. With semaglutide 2.4 mg, more patients achieved HbA1c <7% and weight loss ≥10% (composite endpoint) vs. PBO or semaglutide 1.0 mg, and reduced OAD use vs. PBO.

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Disclosure

L. 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. T. A. Wadden: Advisory Panel; Self; Novo Nordisk, Weight Watchers International, Inc. 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. 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. L. Færch: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. 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. A. Pakseresht: Employee; Self; Novo Nordisk A/S. S. Pedersen: Advisory Panel; Self; AstraZeneca, Bausch and Lomb Incorporated, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Global Services, LLC., Novo Nordisk, Consultant; Self; Abbott, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Speaker’s Bureau; Self; Abbott Laboratories, AstraZeneca, Bausch and Lomb Incorporated, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi. J. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi. I. Shimomura: Advisory Panel; Self; AstraZeneca K. K., Daiichi Sankyo, Novo Nordisk Pharma Ltd., Taisho Pharmaceutical Co., Ltd., Consultant; Self; MSD

Funding

Novo Nordisk A/S

© 2021 by the American Diabetes Association
2021
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