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Significant weight loss achieved by semaglutide in obese patients without diabetes

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The antidiabetic drug semaglutide is used in combination with diet and exercise to treat under-controlled type 2 diabetes. However, it is currently unclear whether this drug will lead to weight loss in obese non-diabetic patients.

Obesity is a major public health concern and is associated with adverse cardiovascular conditions such as dyslipidemia, hypertension, type 2 diabetes and increased mortality. Weight management programs generally focus on reducing calorie intake (due to diet) and increasing energy expenditure (due to exercise), but maintaining weight loss overtime remains difficult. The glucagon-like peptide 1 analog, semaglutide, is approved for the management of type 2 diabetes and for reducing the risk of cardiovascular events in patients with both diabetes and cardiovascular disease. But can this drug play a role in weight loss in patients without overt diabetes? This is a question raised by a team at Northwestern University’s Fineberg School of Medicine in Illinois, which conducted a 68-week randomized placebo-controlled trial in overweight and obese patients. In this study, the body mass index (BMI) of people with one or more weight-related comorbidities, including hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease but not type 2 diabetes. ) Enrolled more than 30 or 27 patients. Participants were randomized to weekly subcutaneous semaglutide or a corresponding placebo and lifestyle intervention at a dose of 2.4 mg. The initial dose of semaglutide was 0.25 mg for the first 4 weeks and was increased every 4 weeks, so by week 16 all participants received the target dose (ie 2.4 mg). Lifestyle advice included individual counseling sessions every four weeks to help with compliance with a daily shortage of 500 kcal and increased physical activity (150 minutes per week). The primary endpoints were the rate of change in body weight (from baseline) to the end of the study (week 68) and the achievement of at least 5% of body weight.

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In total, 1961 participants were randomized in a 2: 1 ratio to semaglutide (1306) or placebo (655). The average age of patients receiving semaglutide was 46 years (73.1% female), of whom 64.5% had a BMI of 30-40 and 29.3% had a BMI above 40. The most common comorbidities were dyslipidemia (38.2%) and hypertension. (36.1%). Patients assigned to semaglutide showed weight loss after week 4, and by the end of the study, 69.1% of participants assigned to the drug achieved weight loss of 10-15% of their initial body weight. , 32% lost more weight. over 20. This was compared to 12% and 1.7% of patients who received placebo, respectively. The overall average weight loss of those taking semaglutide was -14.9% (p <0.001), compared to -2.4% when taking placebo. The semaglutide group also saw a significant improvement in cardiovascular risk factors compared to placebo. The most common side effects are the gastrointestinal tract (usually nausea, diarrhea, vomiting), which was more common in patients receiving semaglutide, but these are generally mild to moderate severity and continuous treatment. It was solved with. However, more patients taking semaglutide discontinued due to side effects (4.5% vs 0.8%).

In their conclusion, the authors reported that semaglutide resulted in substantial and sustained weight loss in people without type 2 diabetes.

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Wilding JPH et al. Weekly semaglutide in overweight or obese adults. New Eng J Med 2021 https://www.nejm.org/doi/full/10.1056/NEJMoa2032183

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