Research in context
Evidence before this study
Weight loss has been shown to improve glycaemic control and reverse disease progression in people with type 2 diabetes. GLP-1 receptor agonists have shown efficacy in lowering glycated haemoglobin (HbA1c) and decreasing weight in patients with type 2 diabetes. Once a week semaglutide 2·4 mg is currently being investigated as an obesity pharmacotherapy.
We searched PubMed on Nov 24, 2020, for articles published in the past 5 years, with no language restrictions, using the search terms “glucagon-like peptide-1 receptor agonist”, “obesity”, and “overweight”. The SCALE Diabetes trial of once a day liraglutide 3·0 mg as an adjunct to lifestyle intervention in patients with overweight or obesity, and type 2 diabetes (n=846) reported a reduction in bodyweight of 5·4% from baseline. In a phase 2, dose-finding trial (n=957), once a day subcutaneous semaglutide 0·4 mg showed effective weight loss and an acceptable safety profile.
Added value of this study
In adults with overweight or obesity and type 2 diabetes, once a week semaglutide 2·4 mg achieved a superior decrease in mean bodyweight (−9·6% [SE 0·4]) compared with semaglutide 1·0 mg (−7·0% [SE 0·4]) and placebo (−3·4% [SE 0·4]), with clinically meaningful reductions (at least 5%) reported in more than two-thirds of patients on semaglutide 2·4 mg. Furthermore, more than two-thirds of patients treated with semaglutide 2·4 mg achieved a target HbA1c of 6·5% or lower. Semaglutide 2·4 mg also resulted in improvement in cardiometabolic risk factors compared with placebo. The safety profile of semaglutide 2·4 mg was typical of a GLP-1 receptor agonist.
Implications of all the available evidence
This is the first trial to show that in adults with overweight or obesity and type 2 diabetes, once a week subcutaneous semaglutide 2·4 mg produces clinically meaningful reductions in bodyweight. The magnitude of weight loss achieved with semaglutide 2·4 mg in STEP 2 was greater than that seen with liraglutide and other approved anti-obesity medications in similar patient populations. Semaglutide 2·4 mg is a promising treatment option for weight management in patients with overweight or obesity and type 2 diabetes.