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 - PubMed (original) (raw)

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

Michelle E Orme et al. Diabetes Metab Syndr Obes. 2017.

Abstract

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 A1C target of <7% were analyzed with a binomial model and change in A1C from baseline with a normal model. A covariate analysis assessed the impact of baseline A1C and treatment background on outcomes.

Results: The base-case NMA used 23 trials reporting A1C outcomes at ~6 month follow-up. The results, unadjusted and adjusted for baseline A1C, indicated that all GLP-1 RAs resulted in statistically significantly lower A1C 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 A1C 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% A1C target within 6 months of commencing GLP-1 RAs.

Conclusion: This was a comprehensive assessment of the comparative effectiveness of GLP-1 RAs and A1C outcome. GLP-1 RAs are a viable addition to oral antidiabetes therapy, and dulaglutide, exenatide once weekly, and liraglutide are the most effective.

Keywords: GLP-1 RAs; comparative effectiveness; glucagon-like peptide-1-receptor agonists; network meta-analysis; type 2 diabetes.

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Conflict of interest statement

Disclosure MEO received funding from AstraZeneca US, and HN, JL, and SAT are paid employees of AstraZeneca US. The authors report no other conflicts of interest in this work.

Figures

Figure 1

Figure 1

Network diagram for meta-analysis of A1C outcomes. Notes: Network 2 includes all 29 studies, network 1 (the base case) excludes LEAD-3 and HARMONY 1–5– (23 studies); line thickness corresponds to number of study arms contributing to analysis. Abbreviations: EBID, exenatide bis in die (twice daily); EQW, exenatide quaque week (once weekly); Dula, dulaglutide; Ins, insulin; Albi, albiglutide; Lira, liraglutide; Met, metformin; Tzd, thiazolidinedione; Pla, placebo; Su, sulfonylurea; DPP4i, DPP4 inhibitor; Sita, sitagliptin.

Figure 2

Figure 2

Summary of network meta-analysis results: absolute change in A1C and probability of reaching <7% treatment target. Notes: RE, random effect; CrI, credible interval; Pla, placebo; Albi, albiglutide; Dula, dulaglutide; EBID, exenatide bis in die (twice daily); EQW, exenatide quaque week (once weekly); Lira, liraglutide; Su, sulfonylurea; Ins, insulin; Met, metformin; Tzd, thiazolidinedione; DPP4i, dipeptidyl peptidase-4 inhibitor.

Figure 3

Figure 3

Direct meta-analysis results: odds of reaching <7% treatment target for exenatide 10 μg twice daily versus placebo. Abbreviations: OR, odds ratio; CI, confidence interval; DL, DerSimonian–Laird (random-effect model); MH, Mantel–Haenszel (fixed-effect model).

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