Incretin-based drugs not associated with any increase in risk for pancreatic diseases

The findings may reassure prescribers of dipeptidyl peptidase-4 inhibitors that the drug class does not significantly increase the risk of adverse pancreatic outcomes compared with other second-line therapies, study authors said.


No significant differences were found in the risk of pancreatic diseases among patients taking any of the second-line antihyperglycemic drug classes, according to a recent study.

Researchers used a dataset of ambulatory and primary care medical practices generally representative of the U.S. population to study people with type 2 diabetes diagnosed after 2004 who received metformin plus a dipeptidyl peptidase-4 inhibitor (DPP-4) (n=50,095), glucagon-like peptide-1 (GLP-1) receptor agonist (n=12,654), sulfonylurea (n=110,747), thiazolidinedione (n=17,597), or insulin (n=34,805) for at least three months. The researchers estimated time to developing acute pancreatitis and other diseases of the pancreas and pancreatic cancer while balancing and adjusting antihyperglycemic drug groups for confounders. The study results were published Oct. 10 by Diabetic Medicine.

There were 1,049 (0.46%) people who developed acute pancreatitis during the mean 3.2 years of follow-up. The rates of acute pancreatitis per 1,000 person-years were similar with DPP-4 inhibitors (1.31; 95% CI, 1.21 to 1.59), GLP-1 receptor agonists (1.49; 95% CI, 1.16 to 1.92), and sulfonylureas (1.45; 95% CI, 1.33 to 1.58). Patients treated with insulin had a significantly higher rate of acute pancreatitis (2.01; 95% CI, 1.75 to 2.31) compared with the DPP-4 inhibitor group, while those treated with a thiazolidinedione had a significantly lower rate (0.89; 95% CI, 0.70 to 1.12). The adjusted mean time to acute pancreatitis in people treated with a DPP-4 inhibitor was 2.63 years (95% CI, 2.38 to 2.88 years).

Compared with the DPP-4 inhibitor group, patients in the insulin group developed acute pancreatitis 0.48 year earlier (P<0.01), and the GLP-1 receptor agonist group developed pancreatic cancer three years later (P<0.01). However, the time to acute pancreatitis was no longer significantly different between the insulin and DPP-4 inhibitor groups after patients who developed acute pancreatitis or other diseases of the pancreas or any cancer within six months of the index date were excluded.

The study authors noted that previous research had indicated a potential relationship between the use of incretin-based antidiabetic drugs, particularly the DPP-4 inhibitor class, and adverse pancreatic outcomes. Limitations of this study include that complete longitudinal data related to medication adherence and tobacco and alcohol exposure were not available and that the study couldn't adjust for other conditions known to be linked with pancreatitis and pancreatic cancer, according the authors. “The findings of this analysis provide reassurance to prescribers and users of [DPP-4 inhibitors] that these medications do not significantly increase the risk of adverse pancreatic outcomes compared with other commonly prescribed second-line therapies,” they said.