Use of dipeptidyl peptidase-4 inhibitors (DPP-4is) is associated with an increased risk for pancreatitis and pancreatic cancer in patients with newly diagnosed type 2 diabetes, according to study results published in Diabetes Care.

DPP-4is are incretin-based agents known to have effects on pancreatic function. Researchers aimed to investigate the risk for pancreatitis and pancreatic cancer associated with the use of DPP-4is in patients newly diagnosed with type 2 diabetes from the Korean National Health Insurance Service–Health Screening Cohort database.

Data were obtained from a total of 33,208 patients (42.2% women), including 10,218 DPP-4i users and 22,990 individuals treated with other antidiabetic drugs (DPP-4i nonusers). The DPP-4is prescribed included sitagliptin, vildagliptin, linagliptin, saxagliptin, and gemigliptin. Primary outcomes were the incidence of pancreatitis and pancreatic cancer. Additional data including age, sex, body mass index, smoking status, alcohol intake, and medical history were also obtained for use in subgroup analyses.

A total of 1084 cases of pancreatitis were observed, with an incidence rate of 1073 per 100,000 person-years for DPP-4i users and 935 per 100,000 person-years for DPP-4i nonusers. After adjusting for confounding factors, the use of DPP-4is was associated with a significantly higher risk for pancreatitis (adjusted hazard ratio, 1.27; P =.007). A Cox proportional hazards model analysis found no significant effect on the risk for pancreatitis based on the duration of DPP-4i exposure. Subgroup analyses also indicated that potential confounding factors did not significantly affect the association between DPP-4is and pancreatitis.

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Pancreatic cancer was diagnosed in 237 patients at an incidence rate of 236 and 200 per 100,000 person years for DPP-4i users and nonusers, respectively. After adjusting for confounding factors, use of DPP-4is was associated with a significantly higher risk for pancreatic cancer (adjusted hazard ratio, 1.50; P =.04). The risk for pancreatic cancer was similar across groups regardless of the time since prescription. Subgroup analyses also found that potential confounding factors did not have an impact on the risk for pancreatic cancer associated with DPP-4i use.

The researchers noted that reverse causation could not be excluded, as the duration of exposure to DPP-4is was not associated with an increased risk for pancreatitis or pancreatic cancer. DPP-4is are preferentially used in patients with severe hyperglycemia, which may preclude pancreatitis or pancreatic cancer. Further studies with an extended duration of treatment are warranted to clarify the relationship between DPP-4i use and pancreatic safety.

“Collectively, the results of the current study demonstrated that DPP-4i use was associated with increased risks of pancreatitis and pancreatic cancer in patients with newly diagnosed type 2 diabetes,” the researchers concluded. “[L]ong-term pancreatic safety of DPP-4i has to be further investigated and physicians should develop better strategies to monitor the DPP-4i use in clinical settings, particularly in patients with newly diagnosed type 2 diabetes.”

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Reference

Lee M, Sun J, Han M, et al. Nationwide trends in pancreatitis and pancreatic cancer risk among patients with newly diagnosed type 2 diabetes receiving dipeptidyl peptidase-4 inhibitors [published online August 20, 2019]. Diabetes Care. doi:10.2337/dc18-2195