Clinical Question

Is once-weekly subcutaneous semaglutide (Ozempic) an effective adjunct to intensive behavioral therapy for adults without diabetes mellitus who are overweight or obese?

Bottom Line

Once-weekly subcutaneous semaglutide used as an adjunct to intensive behavioral therapy significantly improves the likelihood that adults without diabetes who are overweight or obese will lose at least 5% of their baseline body weight compared with placebo (number needed to treat = 2.4). (Level of Evidence = 1b)

Synopsis

Although semaglutide helps reduce weight and improve glucose control in adults with type 2 diabetes, its effectiveness as an adjunct for weight loss in adults without diabetes who are overweight or obese is uncertain. The investigators identified adults without diabetes, 18 years or older, who reported at least one unsuccessful dietary effort to lose weight and had a body mass index (BMI) of 27 kg per m² or higher with at least one weight-related comorbidity (e.g., cardiovascular disease, hyper-lipidemia, hypertension, obstructive sleep apnea) or a BMI of 30 kg per m² or higher. Most patients were women (81%) and White (76%) with a mean age of 46 years and mean BMI of 38 kg per m². Eligible patients (n = 611) randomly received (concealed allocation assignment) once-weekly subcutaneous semaglutide (initially 0.25 mg, with dose titrated as tolerated every four weeks to a target dosage of 2.4 mg per week at week 16) or matched placebo. Participants also received a low-calorie diet (1,000 to 1,200 kcal per day) for the first eight weeks, followed by 1,200 to 1,800 kcal per day for the remainder of the 68 weeks. In addition, all participants received an exercise prescription and 30 individual intensive behavioral visits with a dietitian. Complete follow-up occurred for 92.8% of participants at 68 weeks.

Using intention-to-treat analysis, participants in the semaglutide group lost significantly more weight than in the placebo group (estimated mean body weight change from baseline: −16.0% for semaglutide vs. −5.7% for placebo). More participants treated with semaglutide lost at least 5% of baseline body weight compared with participants treated with placebo (86.6% vs. 47.6%, respectively; number needed to treat = 2.4; 95% CI, 2.1 to 3.0). Significantly more participants treated with semaglutide achieved weight losses of at least 10% and 15% compared with participants treated with placebo.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry

Allocation: Concealed

Setting: Outpatient (any)

Reference: Wadden TA, Bailey TS, Billings LK, et al. STEP 3 InvestigatorsEffect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial. JAMA. 2021;325(14):1403–1413.