Pancreatic Cancer Not Associated with Incretin Drugs

Study results indicate that risk increased similarly for all glucose lowering agents.

Previous observational studies have linked incretin-based drugs such as GLP-1 mimetics and DPP4-inhibitors to an increased risk of pancreatic cancer. However, large trials such as SAVOR-TIMI and EXAMINE found no difference between DPP4-inhibitor treatment and placebo with regards to pancreatic cancer. Therefore, researchers conducted a study to examine the risk of pancreatic cancer with incretin-based drugs when compared with other glucose lowering agents.

The study was a case-control study from 2005-2012 using population-based medical databases, which consisted of 6,036 pancreatic cancer cases and 60,360 controls. Odds ratios (OR) for pancreatic cancer associated with the use of incretin-based drugs and other glucose lowering agents were calculated using conditional logistic regression adjusting for other pancreatic cancer risk factors.

A total of 122 patients with pancreatic cancer (2%) vs. 400 controls (0.7%) had used incretin-based drugs at least once, whereas 20.8% cases vs. 8.6% controls had used any glucose lowering agent. Compared with non-users of any glucose lowering agents, the adjusted risk of pancreatic cancer was increased for DPP4-inhibitor users (adjusted OR = 3.87, 95% CI 3.06-4.89) and GLP-1 mimetic users (adjusted OR=2.70, 95% CI 1.82-4.00). Furthermore, the adjusted OR for metformin users was 2.65 (95% CI 2.44-2.88), 2.65 (95% CI 2.41-2.91) for sulfonylurea users, and 3.61 (95% CI 3.24-4.03) for insulin users.

Results indicate that the risk of pancreatic cancer was increased similarly for all glucose lowering agents, which suggests that diabetes is a risk factor for pancreatic cancer, independent of a specific drug effect.

Practice Pearls

• Compared with non-users of any glucose lowering agents, the adjusted risk of pancreatic cancer was increased for DPP4-inhibitor users (adjusted OR = 3.87, 95% CI 3.06-4.89) and GLP-1 mimetic users (adjusted OR=2.70, 95% CI 1.82-4.00).
• Furthermore, the adjusted OR for metformin users was 2.65 (95% CI 2.44-2.88), 2.65 (95% CI 2.41-2.91) for sulfonylurea users, and 3.61 (95% CI 3.24-4.03) for insulin users.
• Results indicate that the risk of pancreatic cancer was increased similarly for all glucose lowering agents, which suggests that diabetes is a risk factor for pancreatic cancer, independent of a specific drug effect.

European Association for the Study of Diabetes 2015 Meeting. Stockholm, Sweden. Abstract 17, presented September 15, 2015.