medwireNews: Findings from a dose-ranging phase II trial published in The Lancet suggest that semaglutide, in combination with lifestyle intervention, may aid weight loss in people with obesity who do not have diabetes.
“Prophylactic use of [glucagon-like peptide-1] receptor agonists in conjunction with diet and lifestyle changes in overweight adults with the goal of reducing adiposity and reducing incident type 2 diabetes might be one of the largest opportunities to influence public health in the future,” say Aaron Kluger and Peter McCullough (both from Baylor Heart and Vascular Institute, Dallas, Texas, USA) in an accompanying commentary.
The study authors, led by John Wilding (University of Liverpool, UK), randomly assigned 957 adults with an average bodyweight of 111.5 kg and an average BMI of 39.3 kg/m2 to receive 1 year of treatment with once daily subcutaneous injections of semaglutide at one of five doses (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg, or 0.4 mg, initiated at 0.05 mg/day and escalated incrementally every 4 weeks until reaching the final dose), liraglutide 3.0 mg/day (initiated at 0.6 mg/day and escalated by 0.6 mg each week), or placebo.
All participants were advised to limit their daily energy intake to approximately 500 kcal below their total energy expenditure, which was estimated from their basal metabolic rate, and were encouraged to do a minimum of 150 minutes of physical activity each week.
At the 1-year follow-up, patients treated with semaglutide experienced dose-dependent reductions in bodyweight from baseline, with mean reductions ranging from 6.0% for participants given the 0.05 mg dose to 13.8% for those given the 0.4 mg dose.
By comparison, patients in the liraglutide group had an average weight loss of 7.8%, while those in the placebo group had an average loss of 2.3%.
All active treatment groups had a significantly greater average reduction in bodyweight at 1 year than patients given placebo, and participants given semaglutide at doses of 0.2 mg and above experienced significantly greater weight loss than those in the liraglutide group, say the researchers.
Wilding and team observe that reductions in bodyweight with the higher doses of semaglutide “appeared to continue through the entire 52-week treatment period,” in contrast to previously reported studies showing that treatment response to liraglutide, lorcaserin, and naltrexone–bupropion plateaued earlier.
They report that semaglutide was “generally well tolerated,” with no unexpected safety signals. Rates of adverse events (AEs), which largely increased with higher doses of semaglutide, were 90–96% in the semaglutide groups, 85% in the liraglutide group, and 79% in the placebo arm. The most commonly reported AEs in the active treatment groups were gastrointestinal, mainly nausea, and the majority of AEs were mild or moderate in severity.
Semaglutide “showed an attractive benefit–risk profile, particularly at the higher doses associated with greater weight loss,” write Wilding and colleagues, who conclude that their findings “support the further development of semaglutide for weight management, for which phase 3 studies are ongoing.”
The commentators note, however, that the dose-related toxicities “almost certainly will influence adherence and sense of wellbeing during treatment.”
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group
See also:
- Semaglutide tops liraglutide for glycemic control in phase II trial
- SUSTAIN 1: ‘high degree’ of glycemic control with semaglutide in type 2 diabetes
- SUSTAIN 2 shows better glycemic control with semaglutide than sitagliptin
- Semaglutide at least equivalent to exenatide on weekly schedule
- SUSTAIN 4: weekly semaglutide a good option after metformin failure
- SUSTAIN 7 published: Semaglutide superior to dulaglutide