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Incretins do not increase risk for pancreatic diseases

Treatment with incretins did not elevate the risk for pancreatitis, pancreatic cancer and other pancreatic diseases among patients with type 2 diabetes treated with metformin, according to research published in Diabetic Medicine.

Treating type 2 diabetes “with glucagon-like peptide-1 receptor agonists (GLP-1RAs) is associated with favorable changes in metabolic measurements such as body weight, and some agents in the class have been shown to reduce the risk of cardiovascular events,” Olga Montvida, PhD student at QIMR Berghofer Medical Research Institute, Brisbane, Australia, and colleagues wrote.

“However, some recent clinical observational studies have raised questions as to the possible association of treatment with incretin-based therapies, particularly with dipeptidyl peptidase-4 inhibitors (DPP-4i), and the risk of acute pancreatitis or pancreatic cancer,” they added.

Montvida and colleagues conducted a study to determine whether initiating second-line anti-hyperglycemic therapy increases the rates and risks of pancreatic cancer, acute pancreatitis or other diseases of the pancreas among patients with type 2 diabetes.

The researchers used the Centricity Electronic Medical Record to identify patients with type 2 diabetes treated with metformin (n = 225,898; mean age, 59 years; 49% men; 69% white) along with a DPP-4i (n = 50,095; 22% of total population), GLP-1RA (n = 12,654; 6%), sulfonylurea (n = 110,747; 49%), thiazolidinedione (n = 17,597; 8%) or insulin (n = 34,805; 15%). They estimated the time to developing the diseases of the pancreas.

Overall, 0.46% of participants (n = 1,049) developed acute pancreatitis during follow-up (mean, 3.2 years). There were similar rates per 1,000 person-years of acute pancreatitis among the DPP-4i (1.31; 95% CI, 1.21-1.59), GLP-1RA (1.49; 95% CI, 1.16-1.92) and sulfonylurea (1.45; 95% CI, 1.33-1.58) groups. However, compared with participants in the DPP-4i group, those in the insulin group demonstrated significantly higher rates of acute pancreatitis (2.01; 95% CI, 1.75-2.31) and those treated with thiazolidinedione demonstrated significantly lower rates (0.89; 95% CI, 0.7-1.12).

The adjusted mean time to acute pancreatitis was 2.63 (95% CI, 2.38-2.88) years, to pancreatic cancer was 2.7 (95% CI, 2.19-3.21) years and to other diseases of the pancreas was 2.73 (95% CI, 2.33-3.12) years among patients receiving DPP-4i. Participants receiving insulin developed acute pancreatitis 0.48 years before those receiving DDP-4i, but this result was insignificant due to no event occurring within 6 months of insulin initiation.

A total of 357 participants (0.16%) developed pancreatic cancer. The groups did not significantly differ in the rate of pancreatic cancer per 1,000 person-years.

Participants receiving GLP-1RA developed pancreatic cancer 3 years later than those receiving DDP-4i. There were no other significant differences in time to event among the other treatment groups.

Other diseases of the pancreas occurred in only 0.33% of participants (n = 752).

“The findings of this analysis provide reassurance to prescribers and users of DPP-4i that these medications do not significantly increase the risk of adverse pancreatic outcomes compared with other commonly prescribed second-line therapies,” Montvida and colleagues concluded. – by Alaina Tedesco

Disclosures: Montvida reports no relevant financial disclosures. The authors report no relevant financial disclosures. Please see study for all other authors’ relevant financial disclosures.