Physicians' Academy for Cardiovascular Education

Sustained body weight loss with GLP-1RA in individuals with overweight or obesity

Once-Weekly Semaglutide in Adults with Overweight or Obesity

Literature - Wilding JPH, Batterham RL, Calanna S, et al. - N Engl J Med. 2021 Feb 10. doi: 10.1056/NEJMoa2032183.

Introduction and methods

Obesity can lead to insulin resistance, hypertension, and dyslipidemia and is associated with type 2 diabetes, CV disease, and nonalcoholic fatty liver disease [1-3]. Lifestyle intervention, such as diet and exercise, is the standard approach for weight management, but challenging to sustain in the long run. Clinical guidelines suggest adjunctive pharmacotherapy, specifically for adults with a BMI of ≥30 kg/m² or ≥27 kg/m² in individuals with comorbidities [1,4,5]. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is approved as an adjunct to diet and exercise to improve glycemic control in adults with T2DM and to reduce MACE in adults with T2DM and established CVD [6]. In a phase 2 trial, semaglutide induced weight loss in individuals with T2DM and in adults with obesity [7-9].

This phase 3 Semaglutide Treatment Effect in People with Obesity (STEP 1) study assessed the efficacy and safety of semaglutide versus placebo as an adjunct to lifestyle intervention to reduce bodyweight in individuals with overweight or obesity and without diabetes.

The STEP 1 trial was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled individuals from June through November 2018. Adults (≥18 years) with one or more self-reported unsuccessful dietary efforts to lose weight and a BMI of ≥30 kg/m² or ≥27 kg/m² with at least one weight-related comorbidity were included in the study. Participants were randomized (2:1) to 2.4 mg of semaglutide (n=1306) administered subcutaneously once a week or placebo (n=655) in combination with lifestyle intervention. The coprimary endpoints were the percentage change in body weight from baseline to week 68 and the percentage of participants with bodyweight reduction of ≥5% at week 68. The supportive secondary endpoint of body composition (total fat, total lean body mass, and regional visceral fat mass) was analyzed in a subgroup of participants (n=140) that underwent dual-energy x-ray absorptiometry (DXA). Follow-up was 68 weeks.

Main results


The STEP 1 trial showed that adults with overweight or obesity without diabetes, who received semaglutide once-weekly in combination with lifestyle intervention had a significant and sustained body weight loss compared to placebo, with 86.4% of participants attaining at least 5% of weight loss after 68 weeks of treatment.


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