The Risk for Acute Pancreatitis and Cancer Associated with GLP-1 Agonists, Exenatide and Liraglutide: a Meta-analysis of Published Evidence

C Alves1,2, F Batel-Marques1,3, AF Macedo2. 1University of Coimbra, School of Pharmacy, 3000-548 Coimbra, Portugal, 2University of Beira Interior, Health Sciences Research Centre, 6201-506 Covilhã, Portugal, 3AIBILI, Health Technology Assessment (HTA) Centre, 3000-548 Coimbra, Portugal

Background: The association between GLP-1 receptor agonists, acute pancreatitis, overall and thyroid cancer has been a matter of discussion. Post-marketing cases of acute pancreatitis associated with exenatide twice-daily were reported to FDA, which recommended a product labelling change in 2009. Medullary thyroid neoplasms were observed in rats during pre-clinical studies for both exenatide once-weekly and liraglutide.

Objective: This meta-analysis was conducted in order to evaluate the risk for acute pancreatitis, overall and thyroid cancer associated with both GLP-1 receptor agonists in type 2 diabetic patients.

Methods: Medline, Cochrane Library and clinicaltrials.gov were searched in order to identify RCTs or observational studies evaluating exenatide or liraglutide and reporting data on acute pancreatitis and cancer. Odds ratios (ORs) with 95% CIs were calculated using a random-effects model. Between-study heterogeneity was assessed using I2 statistics.

Results: Of the 178 possible eligible articles, 19 studies met the inclusion criteria. Of these, 3 were retrospective cohort studies which evaluated the risk for acute pancreatitis associated with exenatide and the remaining randomized controlled clinical trials. Neither exenatide (OR 0.66 [95%CI 0.53 - 1.23], I2=42%) or liraglutide (OR 1.31, [95% CI 0.24 - 7.24], I2=0%) were associated with an increased risk for acute pancreatitis. The pooled OR for cancer associated with exenatide was 0.86 (95% CI 0.29, 2.60, I2=0%). Liraglutide was associated with a non-significant increased risk for cancer (OR 1.35 [95% CI 0.70, 2.59], I2=0%). Liraglutide was not associated with thyroid cancer (OR 1.54 [95%CI 0.40-6.02], I2=0%). For exenatide, no thyroid malignancies were reported.

Conclusion: We found no association between GLP-1 receptor agonists use and AP. A non-significant increase in risk for cancer was seen in patients treated with liraglutide, although the short duration of studies evaluated precludes any definitive conclusion.