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2-Year Effects of Semaglutide in Adults With Overweight or Obesity
TAKE-HOME MESSAGE
- This placebo-controlled randomized trial investigated the efficacy and safety of once-weekly subcutaneous semaglutide administration as long-term treatment in adults with obesity or in those who are overweight with at least one weight-related comorbidity (excluding diabetes). At 104 weeks, treatment with semaglutide was associated with a −15.2% mean change in body weight (treatment difference, −12.6% points) and a significantly higher likelihood of achieving weight loss ≥5% from baseline compared with placebo. However, mild to moderate gastrointestinal adverse events were more frequent with semaglutide.
- This study suggests that semaglutide is a safe and effective treatment for patients who are overweight and obese, promoting sustained weight loss over a 2-year period. Large prospective studies are necessary to further characterize the efficacy and long-term safety profile in diverse populations.
abstract
This abstract is available on the publisher's site.
Access this abstract nowThe STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes. The co-primary endpoints were the percentage change in body weight and achievement of weight loss of ≥5% at week 104. Efficacy was assessed among all randomized participants regardless of treatment discontinuation or rescue intervention. From 5 October 2018 to 1 February 2019, 304 participants were randomly assigned to semaglutide 2.4 mg (n = 152) or placebo (n = 152), 92.8% of whom completed the trial (attended the end-of-trial safety visit). Most participants were female (236 (77.6%)) and white (283 (93.1%)), with a mean (s.d.) age of 47.3 (11.0) years, body mass index of 38.5 (6.9) kg m-2 and weight of 106.0 (22.0) kg. The mean change in body weight from baseline to week 104 was -15.2% in the semaglutide group (n = 152) versus -2.6% with placebo (n = 152), for an estimated treatment difference of -12.6 %-points (95% confidence interval, -15.3 to -9.8; P < 0.0001). More participants in the semaglutide group than in the placebo group achieved weight loss ≥5% from baseline at week 104 (77.1% versus 34.4%; P < 0.0001). Gastrointestinal adverse events, mostly mild-to-moderate, were reported more often with semaglutide than with placebo (82.2% versus 53.9%). In summary, in adults with overweight (with at least one weight-related comorbidity) or obesity, semaglutide treatment led to substantial, sustained weight loss over 104 weeks versus placebo. NCT03693430.
Additional Info
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Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial
Nat. Med. 2022 Oct 01;28(10)2083-2091, WT Garvey, RL Batterham, M Bhatta, S Buscemi, LN Christensen, JP Frias, E Jódar, K Kandler, G Rigas, TA Wadden, S WhartonFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Obesity is a chronic, relapsing disease with a substantial morbidity, mortality, and healthcare burden. Drug interventions for the treatment of obesity provide a potential valuable adjunct to lifestyle interventions, which often achieve only limited weight loss that is difficult to maintain. Semaglutide, a glucagon-like peptide-1 analog, is an antidiabetic medication that is approved for chronic weight management in adults with obesity or overweight with at least one weight-related condition1 based on results from the Semaglutide Treatment Effect in People with Obesity (STEP) clinical trial program.
Previous studies in the STEP trial program have been limited to treatment periods of up to just over a year at 68 weeks. The present study, the 2-year STEP 5 trial, was a phase IIIb trial that was conducted to evaluate the long-term effect of once-weekly subcutaneous administration of 2.4-mg semaglutide, compared with placebo, as an adjunct to lifestyle interventions (a reduced-calorie meal plan and advice about physical activity) on body weight and cardiometabolic risk factors in adults with obesity (BMI ≥ 30 kg/m2) or with overweight (BMI ≥ 27 kg/m2) and at least one weight-related comorbidity, without diabetes. The study randomized 304 adults in the United States, Canada, Hungary, Italy, and Spain who were mostly women (78%) and White (93%). On average, they were 47 years old, weighed 106 kg, had a BMI of 38.5 kg/m2, a waist circumference of 115.7 cm, and an HbA1c of 5.7%. The co-primary endpoints were the percentage change in body weight and achievement of a clinically meaningful weight loss of ≥5% at week 104. The investigators found that once-weekly injections of 2.4-mg semaglutide led to an initial reduction in weight that plateaued after approximately week 60 and was maintained until the end of the study at week 104 (2 years), with a 15.2% mean weight loss from baseline with semaglutide compared with a 2.6% weight loss with placebo (P < .0001). In addition, 77% of patients had a meaningful weight loss of at least 5% of their weight, compared with 34% of patients in the placebo group, at 2 years (P < .0001). With respect to cardiometabolic risk factors, semaglutide treatment improved a range of parameters, including waist circumference, blood pressure, HbA1c levels, and lipid levels, as well as reducing fasting insulin and glucose, which may represent an increase in insulin sensitivity. Safety and tolerability were consistent with adverse events seen with this drug class, with no new safety signals.
The take-home message from this STEP 5 clinical trial is that weight loss occurs and is sustainable at least up to 2 years with semaglutide in persons who are overweight without diabetes with one or more comorbidity or in persons with obesity without diabetes. It is noteworthy that the participants were largely women and White. It is not known how generalizable these data are to the wider populations and other ethnic groups. More data are also needed regarding the long-term cardiovascular benefits of semaglutide in targeting obesity. The ongoing SELECT cardiovascular outcomes trial of semaglutide2 has the potential to address this.
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