Studies suggest no elevated risk of pancreatitis with incretin-based drugs

A study and a meta-analysis suggest incretin-based drugs don't increase the risk of pancreatitis in patients with type 2 diabetes.

In a population-based cohort study in the U.K., researchers compared 20,748 new users of incretin-based drugs with 51,712 users of sulfonylureas. Incretin-based drugs included exenatide, liraglutide, sitagliptin, saxagliptin, vildagliptin, and linagliptin, alone or in combination. Sulfonylureas also were used alone or in combination. Patients had started the drugs sometime between Jan. 1, 2007, and March 31, 2012, and were followed until March 31, 2013, or until they were diagnosed with acute pancreatitis, died, or left the practice. The crude incidence rate for acute pancreatitis was 1.45 per 1,000 patients per year for incretin-based drug users and 1.47 for sulfonylurea users (adjusted hazard ratio, 1.00; 95% CI, 0.59 to 1.70), suggesting that incretin-based drugs are not associated with a higher risk of acute pancreatitis than sulfonylureas in type 2 diabetics. Results were published online April 24 by BMJ.

A systematic review and meta-analysis of 60 studies also didn't find an elevated risk of pancreatitis with incretin-based treatment. The researchers analyzed 55 randomized, controlled trials (RCTs) and 5 observational studies (n=353,639) that compared treatment with glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo, lifestyle modification, or other active antidiabetic drugs. Pooled estimates of the RCTs suggested no higher risk of pancreatitis with incretins versus control (odds ratio, 1.11; 95% CI, 0.57 to 2.17). In addition, 4 of the 5 observational studies also showed no increased risk, but one of the case-control studies (n=2,538) did indicate that taking exenatide or sitagliptin was associated with higher odds of acute pancreatitis (adjusted odds ratio, 2.07; 95% CI, 1.36 to 3.13). The authors warned the results “should be interpreted cautiously,” noting that many of the trials had fairly small sample sizes and short follow-up periods and that most patients had less comorbidity than is observed in actual practice. Results were published online by BMJ April 15.

An editorialist wrote that the results of these 2 studies suggest “with low to moderate confidence” that there is no significant increased risk of pancreatitis from incretin-based drugs. Clinicians should share this evidence with patients as part of their decision-making process on drug treatment but should not necessarily assume incretin-based drugs are the “next step” after metformin, he said. The editorial was published online April 24 by BMJ.