Background: as a class of antidiabetic drugs, incretin-based therapies, including dipeptidyl peptidase-4 inhibitors (DPP-4Is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have aroused concerns because of the problems of abdominal pain that may cause withdrawal in people with type 2 diabetes mellitus (T2DM).
Objectives: our research is to systematically review the effects of incretin-based therapies, including dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), on abdominal pain in people with type 2 diabetes (T2DM).
Methods: we searched MEDLINE, Embase, ClinicalTrials.gov and the Cochrane Library from inception through 23 June 2017 to indentify randomized clinical trials (RCTs) assessed safety of incretin-based therapies in T2DM. We used stata and R software for network meta-analysis.
Results: we included 57 RCTs (40,809 participants) in this review, including seven treatments: DPP-4i, GLP-1RAs, four traditional antidiabetic drugs (insulin, metformin, sulfonylureas (SUs) and thiazolidinediones (TZDs)) and placebo. Compared to insulin, DPP-4i and GLP-1RAs increased the risk of abdominal pain with odds ratio (OR) of 2.30 (95% confidence interval (CI) 1.24 to 4.30) and 2.95 (95% CI 1.86 to 4.68). As for SUs, GLP-1RAs increased the risk with OR of 2.20 (95% CI 1.23 to 3.94). Ranking probability analysis showed that insulin and SUs decreased the risk of abdominal pain most with probabilities of 93.4%, 78.3%. On the contrary, DPP-4i and GLP-1RAs indicated a poor performance with probability of 39.6%, 11.9%.
Conclusions: DPP-4i and GLP-1RAs seem to show a higher risk of abdominal pain compared with insulin. Similarly, GLP-1RAs increases the risk versus SUs. Abdominal pain may reduce patients’ compliance with treatment. This study suggests that the clinician should pay attention to the urgency of the corresponding symptoms and treat in time.
This study is supported by the fund from National Natural Science Foundation of China (71673003), but the funder had no role in the whole research process.
Patient or healthcare consumer involvement: none