Gastrointestinal Adverse Events of Dipeptidyl Peptidase 4 Inhibitors in Type 2 Diabetes: A Systematic Review and Network Meta-analysis

Publication date: Available online 18 August 2017
Source:Clinical Therapeutics
Author(s): Shanshan Wu, Sanbao Chai, Jun Yang, Ting Cai, Yang Xu, Zhirong Yang, Yuan Zhang, Linong Ji, Feng Sun, Siyan Zhan
PurposeThe purpose of this study was to systematically evaluate the effect of dipeptidyl peptidase 4 inhibitors on gastrointestinal adverse events in patients with type 2 diabetes.MethodsMEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from inception through April 28, 2016. Randomized controlled trials that compared dipeptidyl peptidase 4 inhibitor–based therapies with placebo and other hypoglycemic agents in type 2 diabetes were included. The duration of studies was at least 4 weeks.FindingsA total of 165 randomized controlled trials and 122,072 patients were included in the study. Dipeptidyl peptidase 4 inhibitors did not increase the incidence of gastrointestinal adverse events after the treatment with alogliptin (odds ratio [OR] = 0.83; 95% CI, 0.59–1.15), linagliptin (OR = 1.11; 95% CI, 0.92–1.35), saxagliptin (OR = 0.96; 95% CI, 0.80–1.15), sitagliptin (OR = 0.95; 95% CI, 0.64–1.14), teneligliptin (OR = 1.50; 95% CI, 0.81–2.77), and vildagliptin (OR = 0.80; 95% CI, 0.63–1.01) compared with placebo. Compared with glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors significantly decreased the incidence of gastrointestinal adverse events with alogliptin (OR = 0.26; 95% CI, 0.15–0.44), linagliptin (OR = 0.43; 95% CI, 0.25–0.74), saxagliptin (OR = 0.28; 95% CI, 0.17–0.46), sitagliptin (OR = 0.24; 95% CI, 0.17–0.35), and vildagliptin (OR = 0.27; 95% CI, 0.18–0.41). Dipeptidyl peptidase 4 inhibitors were not associated with an increased risk of gastrointestinal adverse events relative to metformin and α-glucosidase inhibitors, respectively.ImplicationsThe network meta-analysis found that compared with glucagon-like peptide 1 receptor agonists, metformin, and α-glucosidase inhibitor, dipeptidyl peptidase 4 inhibitors are associated with a lower incidence of gastrointestinal adverse events.



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