GLP-1 receptor agonists and pancreatic safety concerns in type 2 diabetic patients: data from cardiovascular outcome trials

Purpose Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been suggested to be associated with an increased risk of pancreatitis and pancreatic cancer. The aim of this meta-analysis was to collect data from large-scale cardiovascular outcome trials (CVOTs) to assess the effect of GLP-1RAs on the incidence of acute pancreatitis and pancreatic cancer. Methods Database of Medline, Embase, and the Cochrane Central Register of Controlled Trials were extensively searched up to October 10, 2019. Randomized controlled trials were eligible if they compared GLP-RA with placebo as add-on therapy to standard care in T2DM patients, and reported outcomes required for cardiovascular safety studies and events of acute pancreatitis and/or pancreatic cancer. Peto odds ratio (OR) with 95% confidence interval (CI) was calculated for acute pancreatitis and pancreatic cancer. Results Seven CVOTs enrolling 56,004 patients with T2DM were identified, with a median follow-up time ranging from 1.3 to 5.4 years. A total of 180 cases of acute pancreatitis and 108 cases of pancreatic cancer were reported. The risk of either acute pancreatitis or pancreatic cancer with GLP-1-RA treatment was not significantly different from that observed in placebo arm (Peto OR [95% CI] 1.05 [0.78-1.40], P = 0.76, and 1.12 [0.77-1.63], P = 0.56, respectively), and the results remained robust to sensitivity analyses. Conclusion Pooled analysis of CVOTs did not suggest any increased risk of either acute pancreatitis or pancreatic cancer with GLP-1RA treatment in T2DM patients.