Saxagliptin-induced Recurrent Acute Pancreatitis

Abstract

Although dipeptidyl peptidase-4 (DPP-4) inhibitors have been implicated in the development of acute pancreatitis, the causality of this phenomenon is not well established. We herein report the case of an 85-yearold woman who presented with epigastric pain after taking saxagliptin for five months. A high serum lipase level with characteristic computed tomography findings confirmed the diagnosis of acute pancreatitis. The patient's symptoms rapidly resolved after admission, although they recurred when she resumed treatment with saxagliptin for 18 days after discharge. In the absence of any identifiable causes of pancreatitis and considering the temporal sequence of events, the saxagliptin therapy was highly suspected to be the triggering factor. Although drug-induced pancreatitis is rare, treatment with DPP-4 inhibitors should be included as a potential etiology of acute pancreatitis.

Efficacy and safety of DBPR108 (prusogliptin) as an add‐on to metformin therapy in patients with type 2 diabetes: A 24‐week, multi‐centre, randomized, double‐blind, placebo‐controlled, superiority, phase III clinical trial

“…Although causality has yet to be established, acute pancreatitis has been associated with DPP‐4 inhibitor therapy, including saxagliptin, sitagliptin, alogliptin and vildagliptin. 20 , 21 , 22 , 23 , 24 , 25 In this study, no cases of acute pancreatitis were reported. However, only one case of mildly increased pancreatic enzymes was reported in the DBPR108 + metformin group, which recovered at the end of treatment (serum amylase level raised to 132 U/L at week 12 and decreased to 80 U/L at week 24, normal range: 30‐110 U/L).…”

“…Although causality has yet to be established, acute pancreatitis has been associated with DPP-4 inhibitor therapy, including saxagliptin, sitagliptin, alogliptin and vildagliptin. [20][21][22][23][24][25] In this study, no cases of acute pancreatitis were reported.…”

Drug induced pancreatitis: A systematic review of case reports to determine potential drug associations

“…Thus, the risk of AP due to the suspected drug is more easily discerned through the confounding factors and often is different from that gleaned from case report data. For example, an association between oral hypoglycemics and AP has been speculated based upon numerous published case reports [73][74][75]126,159,[287][288][289][290][427][428][429][430][431]491,506,604]; however, systematic review and/or meta-analysis of trial data have demonstrated no association with AP for vildagliptin alone [612] or for dipeptidyl peptidase-4 inhibitors (DPP4i) as a group (i.e., vildagliptin, sitagliptin, saxagliptin, alogliptin, linagliptin, and dutogliptin) [613]. Another systematic review of various study designs concluded that AP during oral hypoglycemic therapy was a rare event and that if an association exists, it is not as strong as originally thought [614].…”

Sixty Years of Drug Discovery for Type 2 Diabetes: Where Are We Now?

“…Animal studies, where -cell mass can be measured directly, show that DPP-IV inhibition preserves (perhaps increases) -cell mass (180). Also not surprising is that acute pancreatitis, and the same associated issues, has also been reported with the DPP-IV inhibitors in some (181,182) but not all (183) studies. While there are no reports of improved cardiovascular outcomes, DPP-IV inhibitors as a class, with perhaps the exception of sitagliptin, appear to be relatively free from major adverse cardiovascular events (184).…”