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

• Published in: Diabetes, metabolic syndrome and obesity Vol. 10; pp. 111 - 122
• Main Authors: Orme, Michelle E, Nguyen, Hiep, Lu, Jackie Y, Thomas, Susan A
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2017; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Care and treatment; Clinical decision making; comparative effectiveness; Decision making; Diabetes; Drug dosages; FDA approval; GLP-1RAs; Glucagon; glucagon-like peptide-1 receptor agonists; Glucose; Glucose monitoring; Hypoglycemia; Insulin; Meta-analysis; network meta-analysis; Original Research; Patients; Risk factors; Type 2 diabetes; United Kingdom > UK; United States > US; comparative effectiveness; GLP-1 RAs; glucagon-like peptide-1-receptor agonists; type 2 diabetes; network meta-analysis
• ISSN: 1178-7007; 1178-7007
• DOI: 10.2147/DMSO.S116810

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. 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 target of <7% were analyzed with a binomial model and change in A from baseline with a normal model. A covariate analysis assessed the impact of baseline A and treatment background on outcomes. The base-case NMA used 23 trials reporting A outcomes at ~6 month follow-up. The results, unadjusted and adjusted for baseline A , indicated that all GLP-1 RAs resulted in statistically significantly lower A 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 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 target within 6 months of commencing GLP-1 RAs. This was a comprehensive assessment of the comparative effectiveness of GLP-1 RAs and A outcome. GLP-1 RAs are a viable addition to oral antidiabetes therapy, and dulaglutide, exenatide once weekly, and liraglutide are the most effective.