Weight loss is a big business, with options limited by efficacy, side effects and cost. New evidence suggests that weekly injections of semaglutide may be another option. Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist primarily used to improve glycemic control in adults with type 2 diabetes. Its use is associated with improved cardiovascular and renal outcomes and reduced all-cause mortality. One favorable side effect of semaglutide is weight loss, and researchers have now studied its use in adults with overweight or obesity and without diabetes.
In this new study, a total of 1,961 adults (74 percent female, mean age 46) with at least one failed attempt at weight loss through diet and either body-mass index (BMI) of over 30 or BMI of 27-30 with one comorbidity, were randomized to weekly subcutaneous injections of semaglutide or to placebo for 68 weeks. Semaglutide dosing was started at 0.25 mg for the first four weeks and increased at four-week intervals up to 2.4 mg. Both groups received monthly counseling which encouraged a reduced calorie diet and 150 minutes of weekly physical activity. Adults with a history of diabetes, pancreatitis, weight loss surgery, or use of weight loss medication were excluded. The co-primary endpoints were percentage change in body weight and reduction of body weight of 5 percent or more from baseline to week 68.
Results were impressive. Intention-to-treat analysis revealed a mean body weight reduction from baseline to 68 weeks of 14.9 percent (or 33.7 lbs/15.3 kg) with semaglutide vs. 2.4 percent (or 5.7 lbs/2.6 kg) with placebo (p < 0.001). Participants who received semaglutide were more likely to lose 10 to 15 percent of baseline body weight and also had greater improvements in waist circumference (-13.5 cm vs. -4.1 cm), systolic blood pressure (-6.16 mm Hg vs. -1.06 mm Hg), and physical functioning scores when compared with placebo at 68 weeks (all comparisons p < 0.001). The most common side effects of semaglutide were nausea and diarrhea but the overall dropout rate was low and adherence to treatment was high.
So, is semaglutide the weight loss drug we’ve been waiting for? While these results are notable, this study was completed in mostly White women who exercised, dieted, and kept a daily food diary, so results may not be generalizable. Additionally, the price tag for semaglutide is high. According to GoodRx, a one-month supply of semaglutide is about $900, which makes the cost of 68 weeks of treatment around $13,000 or the equivalent of $400/pound lost. This cost is similar to surgical weight loss interventions, which have varying degrees of sustained weight loss, something not currently known with semaglutide. Instead of asking if this treatment is really worth the money, maybe we should be asking why monthly lifestyle intervention over 16 months resulted in a weight loss of only 2.4 percent. Semaglutide may be a suitable option as an adjunct to diet and exercise for weight loss, but this study also prompts us to ask what we can do to improve lifestyle interventions in our patients.
For more information, see the topic Weight Loss Medications for Obesity in Adults in DynaMed.
