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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

GLP-1 has a few roles in the body

One of the more interesting aspects is that while the CS exposure depletes the ELF, plasma, and liver GSH levels, the lung tissue GSH levels remain unchanged

doi: 10.1002/cne.902730204 28 PanulaPAiraksinenMSPirvolaUKotilainenE

Over months, significant weight loss supports metabolic health: better blood pressure, improved insulin sensitivity, and smaller waist measurements for many patients