Efficacy and Safety of Glucagon-Like Peptide 1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Network Meta-analysis.

INTRODUCTION: The present study aimed to evaluate the effects of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on clinical and safety outcomes including glycemic control and cardiometabolic indicators using network meta-analysis. METHODS: MEDLINE, Embase, and Cochrane Library Central Register of Controlled Trials were searched from inception through June 30, 2019. Randomized clinical trials comparing one or more of six eligible GLP-1RAs with placebo or another eligible GLP-1RA were identified. We further screened studies that had 24-30 week follow-up periods and target endpoints. The primary outcome was change in hemoglobin A (HbA). Secondary outcomes included additional glycemic control indicators, cardiometabolic measures, and adverse events. Frequentist random-effect network meta-analyses were conducted for effect comparison. RESULTS: The NMA synthesized evidence from 54 studies covering 23,209 patients and 18 GLP-1RA regimens. All included GLP-1RA regimens except liraglutide 0.3 mg once weekly (QW) significantly lowered HbA after 24-30 weeks compared with placebo. The pairwise comparison of HbA-lowering effect showed that dulaglutide 0.75 mg QW, dulaglutide 1.5 mg QW, exenatide 2 mg QW, liraglutide 0.9 mg QW, liraglutide 1.2 mg QW, liraglutide 1.8 mg QW, loxenatide 100 µg QW, and loxenatide 200 µg QW were not significantly outperformed by any of the other regimens. The effects on blood pressure, weight, and lipids were relatively mixed. The GLP-1RA regimens had comparable safety profiles with regard to hypoglycemia and adverse events. CONCLUSION: Regimens of GLP-1RAs had differential glycemic control and cardiometabolic effectiveness. Policymaking and patient-centric clinical decisions should take into consideration the comparative effectiveness profiles.