Gastrointestinal Adverse Events of Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis

Abstract

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a new class of drugs used in the treatment of type 2 diabetes mellitus (T2DM). Gastrointestinal (GI) adverse events (AEs) are the most frequently reported treatment-related AEs for GLP-1 RAs. We aim to evaluate the effect of GLP-1 RAs on the incidence of GI AEs of T2DM. Materials and Methods: The overview of the GI events of GLP-1 RAs has been performed on relevant publications through the literature search, such as MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov The manufacturer was contacted regarding unpublished data. We analyzed direct and indirect comparisons of different treatments using Bayesian network meta-analysis. Results: Taspoglutide 30 mg once weekly (TAS30QW) and lixisenatide 30 lg twice daily (LIX30BID) were ranked the top two drugs in terms of GI AEs versus placebo. The odds ratios of nausea and vomiting for TAS30QW were 11.8 (95% confidence interval [CI], 2.89, 46.9) and 51.7 (95% CI, 7.07, 415), respectively, and that of diarrhea was 4.93 (95% CI, 1.75, 14.7) for LIX30BID. Conclusions: Our study found all GLP-1 RA dose regimens significantly increased the incidence of GI AEs, compared with placebo or conventional treatment. The occurrence of GI AEs was different with diverse dose regimens of GLP-1 RAs. TAS30QW had the maximum probability to occur nausea and vomiting, whereas LIX30BID had the maximum probability to cause development of diarrhea versus other treatments.

Gut feelings about diabetes and GLP‐1 receptor agonists: lessons to be learnt from studies in functional gastrointestinal disorders

“…The observations of Bettge et al are consistent with those of other recent meta‐analyses of GLP‐1 RA trials, and inform clinical practice in regard to optimal selection within this drug class. The authors recognize the limitations of heterogeneous study populations and the lack of consistency in symptom data collection among studies.…”

“…The profile of GI adverse events, particularly nausea and vomiting, differs between members of the GLP‐1 RA class . A key distinction between GLP‐1 RAs is that some are “short‐acting,” exhibiting plasma concentrations that peak rapidly after subcutaneous administration before becoming undetectable after several hours (eg, exenatide BID and lixisenatide), while others are “longer‐acting” (eg, exenatide QW, liraglutide, albiglutide and dulaglutide) and have much more stable plasma concentrations over time, allowing administration once daily, once weekly or even less frequently.…”

Upper and/or lower gastrointestinal adverse events with glucagon‐like peptide‐1 receptor agonists: Incidence and consequences

“…In patients with type 2 diabetes (T2D), glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) lead to significant reductions in glycated haemoglobin (HbA1c) levels and body weight, and are now approved and used across the spectrum of T2D therapies, as an adjunct to diet and exercise, oral agents or insulin . GLP‐1RAs are associated with gastrointestinal adverse events (AEs), predominantly nausea, vomiting and diarrhoea.…”

Glucagon like peptide-1 receptor agonist (GLP-1RA) therapy in management of type 2 diabetes: choosing the right agent for individualised care

“…68 Longer-acting GLP-1RAs were associated with a lower risk of GI side effects (with an exception of albiglutide and once-weekly exenatide) compared to short acting GLP-1RAs (EBID, lixisenatide). 25,27,50 Of the two short acting GLP-1RAs, lixisenatide demonstrated a lower rate of GI side effects than EBID.…”