OBJECTIVES: The aim of this systematic review is to determine the long-term efficacy, safety, and cost-effectiveness of Glucagon-like peptide-1 (GLP-1) agonist for weight loss and prevention/delay of type 2 diabetes.

METHODS: A thorough search of literature was conducted using specific search terms in the OVID SP platform for Medline, Embase, Cochrane DSR, DARE, CCA, CCTR, CMR, HTA, NHSEED and Econlit. All abstracts and full papers were reviewed according to the eligibility criteria by two reviewers. Data was extracted and risk-of-bias assessed using the Cochrane risk-of-bias tool for randomized trials.

RESULTS: 1550 abstracts and 94 full texts were screened in duplicate. A total of 38 articles were included of which six studies reported cost-effectiveness data and thirty-two RCTs reported long term efficacy and safety outcomes. 32 studies reported that GLP-1 receptor agonists led to weight reduction. Weight reduction for those on liraglutide ranged from 0.7 kg in 52 weeks to 8.4 kg in 68 weeks, and reduction in BMI ranged from 1.0 to 4.2 kg/m² in 52 weeks. Whereas for semaglutide, weight reduction ranged from 3.5 kg to 15.3 kg in 68 weeks and reduction in BMI ranged from 2.9 to 6.6 kg/m² in 68 weeks. Other GLP-1 agonists (efpeglenatide, tirzepatide, and exenatide) also reported consistent weight reductions ranging from 1.7 to 7.3 kg and a reduction in BMI ranging from 2.3 to 2.6 kg/m². Overall GLP-1 receptor agonists improved glycaemic control, blood pressure, and plasma levels of LDL, HDL, and triglycerides. The studies also reported that GLP-1 receptor agonists were safe to use in patients with comorbid conditions. However, GLP-1 receptor agonists were reported to be less cost-effective in treating obesity compared with other class of anti-obesity medications.

CONCLUSIONS: GLP-1 receptor agonists promoted weight reduction, improved metabolic parameters and were considered safe, even though they were less cost effective compared with alternative anti-obesity medications.