No increase in pancreatitis risk with DPP-4 inhibitors, Australian review finds

People with type 2 diabetes treated with a DPP-4 inhibitor are not at higher risk of pancreatic disease than those treated with other anti-hyperglycaemic drugs, a review by Queensland researchers has found.

While some previous studies have suggested a small increased risk of acute pancreatitis in patients using DPP-4 inhibitors, a new review by researchers from the QIMR Berghofer Medical Research Institute in Brisbane has found no difference in rates of any pancreatic diseases between incretins, including GLP-1 receptor agonists and sulfonylureas when used as second line therapy in type 2 diabetes.

The retrospective review evaluated data from 226,000 patients with T2D who were treated with metformin plus DPP-4 inhibitor (50,095 patients), GLP-1 receptor agonist (12,654), sulfonylurea (110,747), thiazolidinedione (17,597) or insulin (34,805) for at least three months.

During an average of 3.2 years of follow up the rates of pancreatic disease were very low, and not significantly different between DPP-4 inhibitors (1.31 per 1000 person years) vs GLP-1 receptor agonist (1.49) and sulfonylureas (1.45).

Rates were lower for thiazolidinediones (0.89/1000 person years) whereas those treated with insulin had higher rates of acute pancreatitis (2.01).

Similar trends were seen in the average time to onset acute pancreatitis, which was 2.63 years for DPP-4 inhibitors and 0.48 years for insulin.

Rates of pancreatic cancer were also very low (0.16%) and there was no difference between treatment groups except for GLP-1 receptor agonists, which had a three-year later time to development of pancreatic cancer than other treatments.

Writing in Diabetic Medicine, the study investigators said the higher rates of pancreatitis seen in insulin users were not surprising, given that these patients were likely to have a greater burden of co-morbidities. The increased risk was no longer significant after adjusting for patients who developed disease within the first six month, they noted.

They said their review was unique in that it included a larger number of “real world” T2D patients than previous reviews and it compared adverse pancreatic outcomes for all treatments rather than a one drug vs all approach

“Our finding that people treated with a DPP-4i are not at higher risk of pancreatic diseases is robust, supported by the sensitivity analyses in a large number of people with Type 2 diabetes.

“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,” they concluded.

The trial was independently funded and the authors declared interests in grants and speaker fees from several pharma companies including Merck Sharp & Dohme and Takeda, which market DPP-4 inhibitors.

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