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

The 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.MEDLINE, 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.A 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.The 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.