Effect of semaglutide and liraglutide in individuals with obesity or overweight without diabetes: a systematic review

Background & Objective: Although data on the effects of liraglutide and semaglutide in patients with diabetes have been reviewed, their therapeutic outcomes in obese/overweight individuals without diabetes have not been summarized. We conducted a systematic review to evaluate their effects on the latter population. Methods: We searched the PubMed, EMBASE, Cochrane, CNKI, and Wanfang databases. Studies regarding obese/overweight adults without diabetes treated with liraglutide/semaglutide compared with other active agents or placebos were accessed. The primary outcomes were the proportions of adults with at least 5% and 10% weight reduction. The secondary outcomes included metabolic indicators and adverse events. Results: Eighteen studies with 10,938 obese/overweight adults without diabetes were included. When stratified by the categories of at least 5% and 10% weight loss, the pooled data showed medians 27.7% and 10.3% of control groups versus 65.3% and 30.7% of liraglutide 3 mg once daily, respectively; whereas medians 47.6% and 20.4% of control groups vs 86.6% and 75.3% of semaglutide 2.4 mg once weekly were found in the two categories, respectively. Both agents either improved or had no impact on lipid or glycemia. Liraglutide or semaglutide therapy had discontinuation rates of 2.4%-11.4% which overlapped with 0.7%-8.6% in control groups. The frequency of adverse events was comparable between the treatment groups and the control groups (66.5%-95.8% vs 46.9%-96.1%), which were mild to moderate graded by studies. Conclusion: Liraglutide and semaglutide therapy led to a clinically relevant (⩾5%) weight loss of 48.2%-88.7% among obese/overweight adults without diabetes. Both liraglutide and semaglutide are associated with weight loss and are well-tolerated.