TOPLINE: 

Incretin-based medications — GLP‑1 receptor agonists and DPP‑4 inhibitors — were not associated with an increased risk for acute pancreatitis among patients with type 2 diabetes (T2D) compared to SGLT2 inhibitors; however, their use was associated with a small increase in risk for biliary disease.

METHODOLOGY: 

• Patients with T2D have higher risks for acute pancreatitis and biliary events, and evidence is mixed on whether incretin-based therapies affect these risks.
• Researchers analyzed three major US claims databases to assess the risk for acute pancreatitis and biliary events among adult patients with T2D who initiated treatment with GLP‑1 receptor agonists, DPP‑4 inhibitors, or SGLT2 inhibitors; those with prior pancreatitis, pancreatic or biliary cancer, biliary disease, or bariatric surgery were excluded.
• They compared data from 591,423 patients who received GLP-1 receptor agonists with data from 675,991 who received SGLT2 inhibitors; 436,800 who received SGLT2 inhibitors vs 844,366 who received DPP-4 inhibitors; and 538,196 who received GLP-1 receptor agonists vs 927,298 who received DPP-4 inhibitors.
• The outcome of interest was hospitalization for acute pancreatitis or a biliary event.

TAKEAWAY:

• Compared with the use of SGLT2 inhibitors, the use of GLP-1 receptor agonists and DPP-4 inhibitors was associated with a similar risk for acute pancreatitis (hazard ratio [HR], 1.01; 95% CI, 0.90-1.13 and HR, 1.00; 95% CI, 0.85-1.15, respectively).
• The use of both GLP-1 receptor agonists and DPP-4 inhibitors vs SGLT2 inhibitors was associated with a modestly increased risk for biliary disease (HR, 1.15; 95% CI, 1.05-1.26 and HR, 1.22; 95% CI, 1.03-1.46, respectively); however, this risk corresponded to fewer than one additional biliary event per 1000 person-years.
• No significant difference in the risk for acute pancreatitis or biliary disease was found between the use of GLP-1 receptor agonists and DPP-4 inhibitors.

IN PRACTICE:

"Our finding of an increased risk of biliary disease with incretin-based therapies, which is consistent with previous evidence, highlights a need for cautionary clinical benefit–risk evaluation when prescribing GLP-1RAs [GLP-1 receptor agonists] or DPP-4is [DPP-4 inhibitors] in patients with T2D at risk of biliary disease," the authors wrote.

SOURCE: 

The study was led by Yichen E. Fang, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School in Boston. It was published online in Diabetes Care.

LIMITATIONS: 

Despite adjusting for more than 90 potential confounders and confounder proxies, residual confounding from unmeasured or incompletely measured factors such as BMI, diet, alcohol consumption, or socioeconomic factors remained unavoidable. Potential misclassification of outcomes may have occurred due to the use of administrative claims data. The exclusion of patients with a history of pancreatitis or biliary events limited the generalizability of the findings. 

DISCLOSURES: 

This study received funding through a grant from the Patient-Centered Outcomes Research Institute. One author received research grants from the National Institute of Diabetes and Digestive and Kidney Diseases and FDA. Some authors disclosed receiving personal fees, grants, and royalties and having other ties with various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.