Incretin-Based Therapy and Risk of Pancreatic Cancer in Patients with Type 2 Diabetes Mellitus: A Meta-analysis of Randomized Controlled Trials

Introduction The present study aims to evaluate the risk of pancreatic cancer with incretin-based therapy among patients with type 2 diabetes mellitus (T2DM). Methods We searched EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for eligible studies published up to March 06 2016. This meta-analysis includes all studies reporting adverse events of pancreatic cancer with use of incretin-based therapies compared with placebo or non-incretin anti-diabetic drugs in patients with T2DM. We used fixed-effect model to compare pooled relative risk (RR) with related 95% confidence intervals (CI). Results A total of 159 randomized trials were identified. Out of these, 135 studies were excluded as pancreatic cancer occurrence had not been included as an end point. The remaining 24 trials enrolling 47,904 participants were further assessed. Overall, no increased risk of pancreatic cancer were detected in association with incretin-based treatment (RR = 0.7, 95% CI 0.37–1.05). The incidence of pancreatic neoplasm was even lower among incretin-based groups than controls (RR = 0.50, 95% CI 0.29–0.87) in trials with duration more than 104 weeks. There was even decreased risk of pancreatic cancer within groups paralleled by incretin-matched placebos (RR = 0.55, 95% CI 0.32–0.93) than by non-incretin anti-diabetic drugs. Neither monotherapy (RR = 0.62, 95% CI 0.38–1.01) nor combination regimen (RR = 0.92, 95% CI 0.45–1.90) of incretin mimetics increased the risk of pancreatic cancer. Conclusion This meta-analysis shows that incretin-based therapies are not associated with increase in the risk of pancreatic cancer. Interestingly, subgroup analyses suggested lower risk of pancreatic cancer in incretin groups than placebo in long-term studies (>104 weeks). Considering the inconsistent results among randomized trials and previous epidemiological investigations, more such studies should be conducted to clarify the existence or non-existence of this association. Funding This work was supported by grants from the National Natural Science Foundation of China (Nos. 81270476 and 81470830).