Jin-Liern Hong, Ph.D., from the University of North Carolina at Chapel Hill, and colleagues examined the risks of acute pancreatitis among U.S. Medicare beneficiaries, aged 66+ years, initiating DDP-4Is versus thiazolidinediones or sulfonylureas.

To examine whether dipeptidyl peptidase four inhibitors (DPP-4I) increase acute pancreatitis risk in older patients and whether the association varies by age, sex, and history of cardiovascular disease (CVD).

A cohort study of DPP-4I initiators versus thiazolidinedione (TZD) or sulfonylurea initiators using U.S. Medicare beneficiaries was conducted, 2007–2014. Eligible initiators were aged 66+ years without a history of a pancreatic disease or alcohol-related diseases.

Patients were followed up for hospitalization due to acute pancreatitis and censored at 90 days after treatment changes. Weighted Cox models were used to estimate the hazard ratio (HR) for acute pancreatitis. Analyses were performed overall as well as within subgroups defined by age, sex, and CVD history.

They found no increased risk of acute pancreatitis comparing 49,374 DPP-4I initiators to 132,223 sulfonylurea initiators (weighted HR 1.01; 95% CI 0.83–1.24) and comparing 57,301 DPP-4I initiators to 32,612 TZD initiators (weighted HR 1.11; 95% CI 0.76–1.62).

Age and sex did not modify the association. Among patients with CVD, acute pancreatitis incidence was elevated in initiators of DPP-4I and sulfonylurea (2.3 and 2.4 per 1,000 person-years, respectively) but not in TZD initiators.

Among patients with CVD, higher risk of acute pancreatitis was observed with DPP-4I compared with TZD (weighted HR 1.84; 95% CI 1.02–3.35) but not compared with the sulfonylurea. Participants had no history of a pancreatic disease or alcohol-related diseases.

The researchers found that the risk of acute pancreatitis was not increased comparing DPP-4I initiators with sulfonylurea initiators (weighted hazard ratio, 1.01; 95% confidence interval, 0.83 to 1.24) and comparing DPP-4I initiators with thiazolidinedione initiators (weighted hazard ratio, 1.11; 95% confidence interval, 0.76 to 1.62). 

The association was not modified by age and sex. Acute pancreatitis incidence was increased for DDP-4I and sulfonylurea initiators but not for thiazolidinedione initiators (2.3 and 2.4 versus 1.5 per 1,000 person-years, respectively), among patients with cardiovascular disease (CVD).

The risk of acute pancreatitis was increased among patients with CVD taking DPP-4Is versus thiazolidinediones (weighted hazard ratio, 1.84; 95 percent confidence interval, 1.02 to 3.35), but not compared to sulfonylureas.

"Our study provides evidence that DPP-4I is not associated with an increased risk of acute pancreatitis in older adults overall," the authors wrote. Several authors disclosed financial ties to the pharmaceutical industry. The positive association observed in patients with CVD could be due to chance or bias but merits further investigation.