Aim: To explore changes in body weight and cardiometabolic risk factors after treatment withdrawal in the STEP 1 trial extension.Materials and Methods: STEP 1 (NCT03548935) randomized 1961 adults with a body mass index ≥ 30 kg/m² (or ≥ 27 kg/m² with ≥ 1 weight‐related co‐morbidity) without diabetes to 68 weeks of once‐weekly subcutaneous semaglutide 2.4 mg (including 16 weeks of dose escalation) or placebo, as an adjunct to lifestyle intervention. At week 68, treatments (including lifestyle intervention) were discontinued. An off‐treatment extension assessed for a further year a representative subset of participants who had completed 68 weeks of treatment. This subset comprised all eligible participants from any site in Canada, Germany and the UK, and sites in the United States and Japan with the highest main phase recruitment. All analyses in the extension were exploratory.Results: Extension analyses included 327 participants. From week 0 to week 68, mean weight loss was 17.3% (SD: 9.3%) with semaglutide and 2.0% (SD: 6.1%) with placebo. Following treatment withdrawal, semaglutide and placebo participants regained 11.6 (SD: 7.7) and 1.9 (SD: 4.8) percentage points of lost weight, respectively, by week 120, resulting in net losses of 5.6% (SD: 8.9%) and 0.1% (SD: 5.8%), respectively, from week 0 to week 120. Cardiometabolic improvements seen from week 0 to week 68 with semaglutide reverted towards baseline at week 120 for most variables.Conclusions: One year after withdrawal of once‐weekly subcutaneous semaglutide 2.4 mg and lifestyle intervention, participants regained two‐thirds of their prior weight loss, with similar changes in cardiometabolic variables. Findings confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health.

Objective: The obesity epidemic is a public health concern, warranting further research into pharmacological treatments for weight management (WM) as an adjunct to lifestyle interventions. The Semaglutide Treatment Effect in People with obesity (STEP) program aims to investigate the effect of semaglutide versus placebo on weight loss, safety, and tolerability in adults with obesity or overweight.Methods: Across five phase 3 trials (NCT03548935, WM; NCT03552757, WM in type 2 diabetes; NCT03611582, WM with intensive behavioral therapy; NCT03548987, sustained WM; and NCT03693430, long‐term WM), ~5,000 participants are being randomly assigned to receive semaglutide 2.4 mg once weekly subcutaneously versus placebo. Results will be available in 2020/2021. For all trials, the primary end point is change from baseline to end of treatment in body weight.Results: Participants have a mean age of 46.2 to 55.3 years, are mostly female (mean: 74.1%‐81.0%), and have a mean BMI of 35.7 to 38.5 kg/m² and a mean waist circumference of 113.0 to 115.7 cm.Conclusions: The STEP program evaluates the efficacy and safety of semaglutide 2.4 mg subcutaneously once weekly in a broad population. The trials will provide insights on WM in people with obesity with and without type 2 diabetes and on long‐term follow‐up. image

Aims: We assessed changes in body composition following tirzepatide treatment in a substudy of participants with obesity or overweight from the SURMOUNT‐1 trial, overall and post hoc in clinically relevant subgroups. Materials and Methods: Substudy participants ( n = 160 of the 2539 in SURMOUNT‐1) underwent dual‐energy X‐ray absorptiometry (DXA) at baseline and Week 72. Body composition parameters were evaluated by analysis of covariance, logistic regression or Fisher's exact test. Post hoc subgroup analyses were conducted by sex (female or male), age (<50, 50 to 15.3 to ≤25.9 kg, or >25.9 kg). Results: The 160 participants (pooled tirzepatide doses n = 124, placebo n = 36) with baseline and end of study DXA data were 73% female and had a mean weight of 102.5 kg and body mass index of 38.0 kg/m ² . The change in body weight, fat mass and lean mass from baseline to Week 72 was −21.3%, −33.9% and −10.9% with tirzepatide and −5.3%, −8.2% and −2.6% with placebo, respectively ( p < 0.001 for all comparisons). Of the body weight lost, approximately 75% was fat mass and 25% was lean mass for both tirzepatide and placebo. These proportions remained consistent across most subgroup analyses. Conclusions: In participants with obesity or overweight from the SURMOUNT‐1 trial, tirzepatide treatment significantly reduced body weight, fat mass and lean mass compared with placebo, while in post hoc analyses, the proportion of body weight lost as fat or lean mass was relatively consistent including in clinically relevant subgroups.