Comparative effectiveness of glycemic control in patients with type 2 diabetes treated with GLP-1 receptor agonists: a network meta-analysis of placebo-controlled and active-comparator trials

BACKGROUND: Clinical studies of patients with type 2 diabetes show that GLP-1 receptor agonists (GLP-1 RAs) improve glycemic control and promote weight loss. We conducted a Bayesian network meta-analysis (NMA) of placebo- and active-controlled randomized trials to assess the comparative effectiveness of liraglutide, albiglutide, dulaglutide, and exenatide twice daily and once weekly, with a focus on glycemic control. MATERIALS AND METHODS: We searched Medline, Embase, and the Cochrane Library (up to December 2014) for core registration programs for US-approved GLP-1 RAs. Patients reaching an A(1C) target of <7% were analyzed with a binomial model and change in A(1C) from baseline with a normal model. A covariate analysis assessed the impact of baseline A(1C) and treatment background on outcomes. RESULTS: The base-case NMA used 23 trials reporting A(1C) outcomes at ~6 month follow-up. The results, unadjusted and adjusted for baseline A(1C), indicated that all GLP-1 RAs resulted in statistically significantly lower A(1C) at follow-up compared with placebo. The odds of reaching the <7% target were also significantly better compared with placebo. With dulaglutide, exenatide once weekly, and liraglutide, the absolute reduction in A(1C) at 6 months was 0.9%–1.4%, and was significantly better than exenatide twice daily. Albiglutide was not significantly different from exenatide twice daily. We estimate that ~50% of patients will meet the <7% A(1C) target within 6 months of commencing GLP-1 RAs. CONCLUSION: This was a comprehensive assessment of the comparative effectiveness of GLP-1 RAs and A(1C) outcome. GLP-1 RAs are a viable addition to oral antidiabetes therapy, and dulaglutide, exenatide once weekly, and liraglutide are the most effective.