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Abstract   Aims  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.

diabetes, obesity and metabolism

Gastrointestinal adverse events with insulin glargine/lixisenatide fixed‐ratio combination versus glucagon‐like peptide‐1 receptor agonist s  in people with type 2 diabetes mellitus: A network meta‐analysis