Gastrointestinal adverse events with insulin glargine/lixisenatide fixed‐ratio combination versus glucagon‐like peptide‐1 receptor agonists in people with type 2 diabetes mellitus: A network meta‐analysis. Issue 1 (22nd October 2020)

• Record Type: Journal Article
• Authors: Rayner, Christopher K.; Wu, Tongzhi; Aroda, Vanita R.; Whittington, Craig; Kanters, Steve; Guyot, Patricia; Shaunik, Alka; Horowitz, Michael
• Is Part Of: Diabetes, obesity & metabolism. Volume 23:Issue 1(2021)
• Page Start: 136
• Page End: 146
• Publication Date: 2020-10-22
• Subjects: Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.14202
• Languages: English
• ISSNs: 1462-8902

Abstract

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.