medwireNews: Findings of the STEP 1 study show marked weight loss in people with obesity but without type 2 diabetes during over a year of treatment with a high dose of semaglutide.
The glucagon-like peptide (GLP)-1 receptor agonist liraglutide at a dose of 3.0 mg/day is already approved specifically for weight management, but requires daily injection, whereas semaglutide is a once-weekly formulation.
“In addition, the weight-loss phase with semaglutide persisted longer than that reported with liraglutide and did not reach the nadir until week 60,” report Robert Kushner (Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA) and co-researchers.
In STEP 1, 1306 participants were randomly assigned to receive semaglutide at a dose of 2.4 mg/week, and a further 655 were given placebo. Both groups also received healthy lifestyle advice, supported by counseling sessions every 4 weeks.
All trial participants had a BMI of at least 30 kg/m2 or of 27 kg/m2 plus one or more weight-related comorbidities. Their average BMI was approximately 38 kg/m2, average age around 47 years, and about three-quarters were female, White, and had at least one co-existing condition. People with diabetes were excluded, but around 40–45% had prediabetes.
After 68 weeks of treatment, people taking semaglutide had lost an average 14.9% of their baseline bodyweight, significantly more than the 2.4% reduction in the people given placebo. The corresponding weight reductions among participants who took their medications as intended throughout the trial were 16.9% and 2.4%.
This “is substantially greater than the weight loss of 4.0 to 10.9% from baseline with approved antiobesity medications,” write Kushner and team in The New England Journal of Medicine.
A total of 86.4% of the semaglutide cohort lost at least 5% of their bodyweight, which the researchers note is “a widely used criterion of clinically meaningful response.” The rate in the placebo group was 31.5%.
In addition, a corresponding 69.1% versus 12.0% of people lost at least 10% of their baseline bodyweight, and 50.5% versus 4.9% lost at least 15%. Furthermore, 32.0% of the semaglutide group lost at least 20% of their bodyweight, which the team says is “approaching” the efficacy seen with some bariatric surgery approaches.
Physical functioning, assessed with the SF-36 and IWQOL-Lite-CT quality of life tools, improved significantly more among people given semaglutide than placebo, which Kushner et al say “is notable given that overweight and obesity significantly impair health-related quality of life.”
Adverse effects were in line with those expected for a GLP-1 receptor agonist, with mild-to-moderate gastrointestinal events the most common. Most of these resolved, but 7.0% of participants discontinued semaglutide because of adverse effects, mostly gastrointestinal, compared with 3.1% who discontinued placebo.
There were also more gallbladder disorders, mostly cholelithiasis, in the semaglutide versus placebo groups (2.6 vs 1.2%). The researchers observe that the incidence of cholelithiasis in the semaglutide group was in line with that seen for the highest approved dose of liraglutide.
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