DPP-4 Inhibitors: Should We Worry About Risk of Pancreatitis?
Although not well recognized until the advent of DDP-4 inhibitors (e.g., alogliptin, linagliptin, saxagliptin, sitagliptin) and GLP-1 agonists (e.g., albiglutide, dulaglutide, exenatide, liraglutide), diabetes is associated with pancreatitis. The mechanisms by which diabetes might lead to pancreatitis are not well understood, although comorbid hypertriglyceridemia and hypertension (which is often treated with thiazides, leading to triglyceride elevation) might be contributing factors.
In the last 2-3 years, case reports of pancreatitis in patients taking GLP-1 agonists and DPP-4 inhibitors have prompted closer scrutiny of the potential relationship between these two classes of agents. Indeed, FDA labeling for some agents from both classes includes warning/caution comments on pancreatitis. Do DPP-4 inhibitors or GLP-1 agonists increase risk for pancreatitis? Recent trial data on saxagliptin provides reassuring commentary that likely merits consideration in reference to other members of the DPP-4 group as well.
Raz et al report data from the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction (SAVOR-TIMI) 53 trial. Among the 16,492 patients randomized to DPP-4 treatment (saxagliptin) or placebo, the risk for pancreatitis was both small (< 0.5%) and not different between saxagliptin and placebo.
Current recommendations suggest that incident pancreatitis in patients taking DPP-4 inhibitors or GLP-1 agonists merits at least temporary discontinuation of such treatment. The SAVOR-TIMI 53 data provide reassurance that DPP-4 inhibitors, specifically saxagliptin, do not increase risk for pancreatitis.
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