A Case of Severe Acute Necrotizing Pancreatitis after Administration of Sitagliptin

Abstract

A 55-year-old Japanese man with a 3-year history of type 2 diabetes mellitus was admitted to our hospital for upper abdominal pain. Control of diabetes mellitus was good with voglibose and metformin, with sitagliptin added to this regimen 8 months prior. His pancreatic enzyme levels were elevated, and abdominal computed tomography (CT) showed diffuse pancreatic swelling with fluid accumulation and ascites of CT grade 3. The patient was diagnosed with severe acute pancreatitis. There were no obvious causes for pancreatitis except the recently administered sitagliptin. Since incretin-related drugs entered the market, the number of incretin-related drugs prescriptions rapidly increased and so did the incidence of pancreatitis. There are several reports suggesting the correlation between incretin-related drugs and pancreatitis, such as a report based on data obtained from the United States Food and Drug Administration (FDA) which revealed a significant correlation between the administration of exenatide or sitagliptin and pancreatitis. However, there also is a report that denied the evidence for such in a large cohort study. The relation between incretin based drugs and pancreatitis is still controversial.

Saxagliptin-induced Recurrent Acute Pancreatitis

“…The latency period in these seven cases ranged from three weeks to eight months. In the present case, the latency period was five months, which is similar to that observed in two Japanese cases and one Indian case (8)(9)(10). Although there is no confirmed mechanism to explain the induction of acute pancreatitis by DPP-4 inhibitors, a hypersensitivity reaction or the accumulation of toxic metabolite(s) has been supposed (13).…”

“…In the literature, there are seven previously reported cases of acute pancreatitis in patients receiving DPP-4 inhibitors (Table) (5)(6)(7)(8)(9)(10)(11). Although the DPP-4 inhibitors, sitagliptin and vildagliptin, were suspected by the authors to be the triggering factors for acute pancreatitis, common risk factors, such as gallstones or mild hypertriglyceridemia, were also present in some cases.…”

“…Thereafter, several large retrospective studies investigating the causal relationship between the administration of incretin-based therapy and acute pancreatitis showed conflicting results (2)(3)(4). However, cases of acute pancreatitis associated with treatment with glucagon-like peptide-1 (GLP-1) agonists or DPP-4 inhibitors continue to be reported worldwide (5)(6)(7)(8)(9)(10)(11). Among the DPP-4 inhibitors, the suspected offending drugs include sitagliptin and vildagliptin.…”

Incretin-based therapies in prediabetes: Current evidence and future perspectives

“…Moreover, discontinuation of therapy because of side effects was similar to placebo [91] . Small preclinical studies, as well as some postmarketing reports, raised the possibility of an increased risk of pancreatitis with incretin based therapies [92][93][94][95][96] . In a study that data were collected from the Food and Drug Administration (FDA) adverse event reporting system database, GLP-1 based therapies were associated with pancreatitis and pancreatic cancer [97] .…”

Pancreatic safety in Japanese patients with type 2 diabetes treated with once weekly dulaglutide 0.75 mg up to 52 weeks in phase 3 clinical trials

“…Some cases of pancreatitis have been reported in Japanese patients with T2D after administration of liraglutide or the DPP-4 inhibitors sitagliptin and vildagliptin [11,12].…”