The latest results from the ongoing Semaglutide Treatment Effect in People With Obesity (STEP) trials are in:
“Among adults with overweight or obesity without diabetes, once-weekly subcutaneous semaglutide compared with once daily subcutaneous liraglutide, added to counseling for diet and physical activity, resulted in significantly greater weight loss at 68 weeks, accompanied by significantly greater improvements in several cardiometabolic risk factors,” Domenica M. Rubino, MD, Washington Center for Weight Management and Research, Arlington, Virginia, and colleagues wrote in JAMA.
The open-label randomized trial compared the efficacy of 2.4 mg once weekly subcutaneous semaglutide against 3.0 mg of once-daily subcutaneous liraglutide, both paired with diet and exercise, for people with overweight or obesity who did not have diabetes. It ran for 68 weeks from September 2019 to May 2021 and took place at 19 U.S. sites.
The study authors recruited participants 18 years or older who reported having trouble with dietary weight loss and whose BMI was 30 or greater or 27 or greater with one or more weight-related comorbidity, including hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease.
“Key exclusion criteria included diabetes, hemoglobin A1c (HbA1c) level of 6.5% (48 mmol/mol) or greater, and self-reported body weight changes of more than 5 kg 90 days or less before screening,” Rubino and colleagues wrote.
The primary end point was change in body weight from baseline to week 68.
Randomization was 3:1:3:1 and the treatments were “not masked (due to dosing differences), but active treatment groups were double-blinded against matching placebo groups to mitigate potential bias arising from open-label comparisons,” the study authors noted. “The placebo groups also facilitated comparisons of semaglutide and liraglutide versus placebo (secondary trial objectives), allowing evaluation of trial results in the context of previous findings.”
There were 126 participants in the semaglutide arm; 127 in the liraglutide arm; and 85 in the placebo group. Most of the participants were White and female. The mean age was 49; mean body weight 104.5 kg; mean BMI 37.5; mean waist measurement 113.3 cm; and about a third had prediabetes.
The treatment groups had similar baseline characteristics, but the placebo group had a higher baseline body weight, more people with higher BMIs, and more people with five or more comorbidities, the study authors noted.
The initial dose of semaglutide was 0.25 mg and titrated up to 2.4 mg, which was considered the maintenance dose, but 1.7 mg was permitted if participants could not tolerate the higher maintenance dose. Liraglutide was started at 0.6 mg and titrated up to 3.0 mg as maintenance over 4 weeks; this higher dose could be delayed by a week to help with tolerability.
Dietary counseling was given every 4-6 weeks with the goal of dietary adherence to a 500-kcal/d deficit relative to baseline energy expenditure and the participants were advised to exercise 150 or more minutes each week.
Most of the participants (94.4%) completed the trial and just over 80% completed treatment.
Among the results:
- Mean weight change from baseline: −15.8% in the semaglutide group versus −6.4% in the liraglutide group (difference, –9.4 percentage points [95%CI, –12.0 to –6.8]; P<.001)
- The pooled placebo group’s weight change was −1.9%
- Confirmatory secondary outcomes showed “[t]he proportions of participants achieving 10% or more, 15% or more, and 20% or more weight loss were 70.9%, 55.6%, and 38.5% with semaglutide and 25.6%, 12.0%, and 6.0% with liraglutide, respectively,” Rubino and colleagues wrote.
- “The odds of achieving weight loss of 10% or more (odds ratio, 6.3 [95%CI, 3.5 to 11.2]), 15% or more (odds ratio, 7.9 [95% CI, 4.1 to 15.4]), and 20% or more (odds ratio, 8.2 [95%CI, 3.5 to 19.1]) were significantly greater with semaglutide versus with liraglutide (P<.001 for all),” they added.
- Treatment was discontinued by 27.6 % of those taking liraglutide, 17.6% placebo, and 13.5% semaglutide.
- The most common adverse events were gastrointestinal—84.1% with semaglutide and 82.7%with liraglutide.
Limitations of the trial include response to the maintenance doses; the semaglutide was stepped down to a lower dose, whereas liraglutide treatment was stopped and then had to be restarted and re-escalated; and participants knew which treatment they could be randomized to, which could have been improved with a double-dummy approach.
Among adults with overweight or obesity without diabetes, once-weekly subcutaneous semaglutide compared with once daily subcutaneous liraglutide, added to counseling for diet and physical activity, resulted in significantly greater weight loss at 68 weeks.
The active treatment groups were double-blinded against matching placebo groups to mitigate potential bias arising from open-label comparisons.
Candace Hoffmann, Managing Editor, BreakingMED™
Rubino reported being a clinical investigator for Boehringer Ingelheim, AstraZeneca, and Novo Nordisk; receiving honoraria from WebMD, speaker fees,consulting fees, scientific advisory fees, and honoraria from Novo Nordisk, grants from SARL, and personal fees from Medscape, PeerView, and the Endocrine Society; and being a shareholder in Novo Nordisk.
Cat ID: 795
Topic ID: 76,795,730,795,518,917