Gastrointestinal adverse events with insulin glargine/lixisenatide fixed-ratio combination versus GLP-1 RAs in people with type 2 diabetes mellitus: a network meta-analysis.

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dc.contributor.authorRayner, C.K.
dc.contributor.authorWu, T.
dc.contributor.authorAroda, V.R.
dc.contributor.authorWhittington, C.
dc.contributor.authorKanters, S.
dc.contributor.authorGuyot, P.
dc.contributor.authorShaunik, A.
dc.contributor.authorHorowitz, M.
dc.date.issued2021
dc.description.abstractAims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are the recommended first injectable therapy in type 2 diabetes. However, long-term persistence is suboptimal and partly attributable to gastrointestinal tolerability, particularly during initiation/ escalation. Gradual titration of fixed-ratio combination GLP-1 RA/insulin therapies may improve GLP-1 RA gastrointestinal tolerability. We compared gastrointestinal adverse event (AE) rates for iGlarLixi versus GLP-1 RAs during the first 12 weeks of therapy, including a sensitivity analysis with IDegLira. Materials and methods: The PICO framework was used to identify studies from MEDLINE, EMBASE and CENTRAL searches using a proprietary, web-based, standardized tool with single data extraction. Gastrointestinal AEs were modelled using a Bayesian network meta-analysis (NMA), using fixed and random effects for each recommended dose (treatment-specific NMA) and class (drug-class NMA). Results: Treatment-specific NMA included 17 trials (n = 9030; 3665 event-weeks). Nausea rates were significantly lower with iGlarLixi versus exenatide 10 μg twice daily (rate ratio: 0.32; 95% credible interval: 0.15, 0.66), once-daily lixisenatide 20 μg (0.35; 0.24, 0.50) and liraglutide 1.8 mg once daily (0.48; 0.23, 0.98). Rates were numerically, but not statistically, lower versus once-weekly semaglutide 1 mg (0.60; 0.30, 1.23) and dulaglutide 1.5 mg (0.60; 0.29, 1.26), and numerically, but not statistically, higher versus once-weekly exenatide (1.91; 0.91, 4.03). Sensitivity analysis results were similar. In a naïve, pooled analysis, vomiting was lower with iGlarLixi versus other GLP-1 RAs. Conclusions: During the first 12 weeks of treatment, iGlarLixi was generally associated with less nausea and vomiting than single-agent GLP-1 RAs. Enhanced gastrointestinal tolerability with fixed-ratio combinations may favour treatment persistence.
dc.description.statementofresponsibilityChristopher K. Rayner, Tongzhi Wu, Vanita R. Aroda, Craig Whittington, Steve Kanters, Patricia Guyot, Alka Shaunik, Michael Horowitz
dc.identifier.citationDiabetes, Obesity and Metabolism, 2021; 23(1):136-146
dc.identifier.doi10.1111/dom.14202
dc.identifier.issn1462-8902
dc.identifier.issn1463-1326
dc.identifier.orcidRayner, C.K. [0000-0002-5527-256X]
dc.identifier.orcidWu, T. [0000-0003-1656-9210]
dc.identifier.orcidHorowitz, M. [0000-0002-0942-0306]
dc.identifier.urihttps://hdl.handle.net/2440/145891
dc.language.isoen
dc.publisherWiley
dc.rights© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
dc.source.urihttps://doi.org/10.1111/dom.14202
dc.subjectGlucagon-like peptide-1 receptor agonists (GLP-1 RAs); type 2 diabetes; injectable therapy
dc.subject.meshHumans
dc.subject.meshDiabetes Mellitus, Type 2
dc.subject.meshPeptides
dc.subject.meshHypoglycemic Agents
dc.subject.meshBayes Theorem
dc.subject.meshGlucagon-Like Peptide-1 Receptor
dc.subject.meshInsulin Glargine
dc.subject.meshNetwork Meta-Analysis
dc.subject.meshGlycated Hemoglobin
dc.titleGastrointestinal adverse events with insulin glargine/lixisenatide fixed-ratio combination versus GLP-1 RAs in people with type 2 diabetes mellitus: a network meta-analysis.
dc.typeJournal article
pubs.publication-statusPublished

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