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Participants saw average hemoglobin A 1C reductions of up to 1.6%

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Findings: RCTSTEP UP Trial - Semaglutide 7.2 mg once weekly vs Semaglutide 2.4 mg once weekly in Obese Adults, Lancet Diabetes Endocrinol (2025) [PubMed abstract] Design: Randomized, double-blind, placebo-controlled and active-controlled trial (N=1407 | length = 72 weeks) in adults with BMI 30 without diabetes Treatment: Semaglutide 7.2 mg once weekly vs Semaglutide 2.4 mg once weekly vs Placebo Primary outcome: Percentage change in body weight and the proportion of participants with a body weight reduction of 5% or greater Results: Primary outcome (% decrease in body weight): Semaglutide 7.2 mg - 18.7%, Semaglutide 2.4 mg - 15.6%, Placebo - 3.9% (p 5kg within 90 days) History of chronic pancreatitis Acute pancreatitis within 180 days Baseline characteristics Average age 48 years Female sex - 79% Average weight - 233 lbs (106 kg) Average BMI - 37.6 Randomized treatment groups Group 1 (205 patients): Oral Semaglutide with a target dose of 25 mg once daily Group 2 (102 patients): Placebo Semaglutide was started at 3 mg daily and increased every 4 weeks to 7 mg, 14 mg, and 25 mg All patients also received diet (500 kcal deficit) and exercise (150 min/week) counseling Coprimary endpoints were the percentage change in body weight from baseline to week 64 and achievement of a reduction in body weight of 5% or more from baseline to week 64 Primary outcome: Results Oral semaglutide at a dose of 25 mg once daily resulted in a greater mean reduction in body weight than placebo in participants with overweight or obesity

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Post-clinical laboratory tests (hematology and serum chemistry) and post-study general and systemic examination, including vital sign measurements (blood pressure, pulse rate and temperature), were performed