Dataset Information

A Network Meta-analysis Comparing Exenatide Once Weekly with Other GLP-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus.

ABSTRACT:

Introduction

Exenatide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA), approved for treatment of type 2 diabetes mellitus (T2DM). There is limited direct evidence comparing the efficacy and tolerability of exenatide 2 mg once weekly (QW) to other GLP-1 RAs. A network meta-analysis (NMA) was conducted to estimate the relative efficacy and tolerability of exenatide QW versus other GLP-1 RAs for the treatment of adults with T2DM inadequately controlled on metformin monotherapy.

Methods

A systematic literature review was conducted to identify randomized controlled trials (RCTs) that investigated GLP-1 RAs (albiglutide, dulaglutide, exenatide, liraglutide, and lixisenatide) at approved doses in the United States/Europe, added on to metformin only and of 24 ± 6 weeks treatment duration. A Bayesian NMA was conducted.

Results

Fourteen RCTs were included in the NMA. Exenatide QW obtained a statistically significant reduction in glycated hemoglobin (HbA1c) relative to lixisenatide 20 µg once daily. No other comparisons of exenatide QW to other GLP-1 RAs were statistically significant for change in HbA1c. No statistically significant differences in change in weight, systolic blood pressure, risk of nausea or discontinuation due to adverse events were observed for exenatide QW versus other GLP-1 RAs.

Conclusion

Exenatide QW demonstrated similar effectiveness and tolerability compared to other GLP-1 RAs, for the treatment of T2DM in adults inadequately controlled on metformin alone.

SUBMITTER: Kayaniyil S

PROVIDER: S-EPMC4801811 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionSemaglutide once-weekly (QW) is a novel glucagon-like peptide-1 (GLP-1) analogue administered at a 0.5 or 1.0 mg dose. In the absence of head-to-head trials between semaglutide QW and other GLP-1 receptor agonists (GLP-1 RAs) in a Japanese population, a network meta-analysis (NMA) was performed. The objective was to assess the relative efficacy and safety of semaglutide QW vs GLP-1 RAs in Japanese patients with type 2 diabetes (T2DM), with a specific focus on the comparison between semaglutide 0.5 mg QW and dulaglutide 0.75 mg QW.MethodsA systematic review (SR) and supplementary Japanese searches were conducted to identify trials of GLP-1 RAs in Japanese patients on diet and exercise, who have previously received 0-1 oral antidiabetic drugs (OADs). Data at 52-56 weeks were extracted for the following outcomes (feasible for analysis in an NMA): glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), weight, systolic blood pressure (SBP), and overall hypoglycemia. The data were synthesized using an NMA and a Bayesian framework.ResultsFour trials, identified from the SR and Japanese-specific searches, were relevant for inclusion in the NMA. When compared to dulaglutide 0.75 mg QW, semaglutide 0.5 mg QW was shown to provide significant reductions in HbA1c [- 0.61% (12.3 mmol/mol)], weight (- 1.45 kg), SBP (- 5.03 mmHg), and FPG (- 1.26 mmol/L). No significant differences in the proportion of patients achieving a HbA1c level < 7% (53 mmol/mol) or the risk of overall hypoglycemia were observed between semaglutide 0.5 mg QW and dulaglutide 0.75 mg QW.ConclusionOverall, semaglutide 0.5 mg QW was associated with significant reductions from baseline in HbA1c, weight, SBP, and FPG compared with dulaglutide 0.75 mg QW in Japanese patients with T2DM. These data may provide valuable evidence for clinical decision-making, cost-effectiveness analyses, and health technology appraisal (HTA) requirements.FundingNovo Nordisk Pharma Ltd.

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