Comparative efficacy and safety of 8 GLP-1RAs in patients with type 2 diabetes: A network meta-analysis

To inform clinical practice by comparing and ranking the lowing blood glucose and weight-loss abilities of 8 glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with type 2 diabetes (T2D).We searched PubMed, EMBASE, and CENTRAL from database inception to April 13, 2021. The outcomes were Δ HbA1c, Δ weight, adverse events [AE] withdrawals, and incidence of hypoglycemia. We estimated standardized mean differences [SMD] and summary odds ratios (ORs) using frequentist network meta-analysis with random effects.Retrieved trials included 11,126 patients, the overall mean age was 56.7 ± 10.36 years old. In terms of efficacy, all GLP-1RAs were more effective than the placebo except albiglutide-30 mg QW (Δ weight: SMD -0.26 kg [95 %CI: -1.10, 0.59 kg). When it came to safety, oral semaglutide-14mgQD, semaglutide-1mgQW, Liraglutide-1.8mgQD, and Exenatide-2ugBID were associated with an increased risk of AE withdrawals. And GLP-1RAs were associated with a higher incidence of hypoglycemia than placebo except albiglutide-30mgQW and orally administered semaglutide-14mgQD.Overall GLP-1RAs were more efficacious than placebo in patients with T2D on efficacy. Unfortunately, differences between GLP1-RAs regarding safety were mostly not significant. We may realize the individualized GLP-1RAs administration based on blood glucose level and obesity degree.