August 27, 2019
2 min read

DPP-IV inhibitors may increase risk for pancreatic cancer

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Adults with type 2 diabetes who are treated with DPP-IV inhibitors are more likely to develop pancreatitis and pancreatic cancer compared with those treated with other medications, according to findings published in Diabetes Care.

“DPP-IV inhibitors are widely used, well-tolerated antidiabetic agents that offer several advantages in clinical settings, especially for medically fragile populations, owing to their favorable efficacy and safety profile,” the researchers told Endocrine Today. “However, there is a concern that DPP-IV inhibitors may adversely impact the exocrine pancreas, owing to their pleiotropic effects. Thus, the pancreatic safety of incretin-based therapies is an important clinical issue to more safely prescribe this useful antidiabetic medication.”

Chung Mo Nam, PhD, of the department of preventive medicine and Eun Seok Kang, MD, PhD, and Minyoung Lee, MD, of the department of internal medicine at Yonsei University College of Medicine in Seoul, South Korea and Jiyu Sun, MSc, biostatistics and computing, at Yonsei University College of Graduate in Seoul, South Korea, assessed the risk for developing pancreatitis and pancreatic cancer in a group of 33,208 adults with type 2 diabetes (mean age, 62.1 years; 42.2% women) in the Korean National Health Insurance Service-Health Screening Cohort database. If an individual had a prescription for at least one of the DPP-IV inhibitors sitagliptin (Januvia, Merck), vildagliptin, linagliptin (Tradjenta, Boehringer Ingelheim/Eli Lilly), saxagliptin (Onglyza, AstraZeneca) or gemigliptin between 2007 and 2013, they were considered to be using this medication class (n = 10,218). DPP-IVs were not used by the remaining 22,990 individuals in the study population. 

The researchers then used the database to confirm instances of pancreatitis and pancreatic cancer over more than 3 years. They found that pancreatitis was diagnosed 1,084 times in the cohort, including 215 instances of chronic pancreatitis and 869 instances of acute pancreatitis. Those using DPP-IV inhibitors experienced pancreatitis 1,073 times per 100,000 person-years, and those on other medications experienced the condition 935 times per 100,000 person-years. DPP-IV inhibitor users were 27% more likely to develop pancreatitis compared with nonusers (adjusted HR = 1.27; 95% CI, 1.07-1.52) and 24% more likely to develop the condition when the researchers considered a 6-month exposure lag period (aHR = 1.24; 95% CI, 1.01-1.52).

anatomy of a pancreas 
Adults with type 2 diabetes who are treated with DPP-IV inhibitors are more likely to develop pancreatitis and pancreatic cancer compared with those treated with other medications.
Source: Shutterstock

DPP-IV inhibitor users experienced pancreatic cancer 236 times per 100,000 person-years and those who used other medications experienced the condition 200 times per 100,000 person-years, with total actual instances of 35 and 202 in the two groups, respectively. The disease was 50% more likely to develop in DPP-IV inhibitor users compared with those using other medications (aHR = 1.5; 95% CI, 1.02-2.2) and 81% more likely when the researchers incorporated a 6-month exposure lag period (aHR = 1.81; 95% CI, 1.16-2.82).

“Based on our data, physicians would develop better strategies to monitor DPP-IV inhibitor use in clinical settings, particularly in patients with newly diagnosed type 2 diabetes,” the researchers said.

The researchers noted that time did not seem to play a role in influencing the risk profiles for pancreatitis and pancreatic cancer, and this could lead to additional interpretations of the results.

“The absence of increasing trend according to exposure duration suggests the chances of reverse causality, and long-term pancreatic safety of DPP-IV inhibitors has to be further investigated,” the researchers said. – by Phil Neuffer

Disclosures: The authors report no relevant financial disclosures.