Pancreatitis and pancreatic cancer in patientes treated with Dipeptidyl Peptidase-4 inhibitors: An extensive and updated meta-analysis of randomized controlled trials

Abstract Aim Observational studies and metanalyses of randomized trials on Dipeptidyl Peptidase-4 inhibitors (DPP4i) reported discordant results on the risk of pancreatitis and pancreatic cancer with this class of drugs. Aim of the present meta-analysis is the assessment of the effect of DPP4i treatment on the incidence of pancreatitis and pancreatic cancer, collecting all available evidence from randomized controlled trials. Methods Data Sources: an extensive Medline, Embase and Cochrane Database search for sitagliptin or vildagliptin or omarigliptin or saxagliptin or alogliptin or trelagliptin or anagliptin or linagliptin or gemigliptin or evogliptin or teneligliptin was performed up to up to September 30th, 2019. All trials performed on type 2 diabetes, with duration ≥24 weeks, and comparing of DPP4i with placebo or active drugs were collected. The study has been registered on PROSPERO (#153344). Mantel-Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for all outcomes defined above. Results A total of 165 eligible trials were identified. DPP-4 inhibitors were not associated with an increased risk of pancreatitis (MH-OR 1.13 [0.86, 1.47]) or pancreatic cancer (MH-OR 0.86 [0.60, 1.24]) with no significant differences across individual molecules of the class. Conclusions: available data do not support the hypothesis of an association of DPP4i treatment with pancreatitis. Present data do not suggest any association of DPP4i with pancreatic cancer, although they are insufficient to draw definitive conclusions.