Brief report
A low-grade increase of serum pancreatic exocrine enzyme levels by dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes

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Abstract

A potential adverse effect of dipeptidyl peptidase-4 inhibitors (DPP-4i) on the pancreas remains controversial. We evaluated the DPP-4i effects on pancreatic amylase and lipase activity in patients with type 2 diabetes. These enzymes were slightly but significantly increased, suggesting DPP-4i cause a low-grade inflammatory change in the exocrine pancreas.

Introduction

Dipeptidyl peptidase-4 inhibitors (DPP-4i) are a new class of therapeutic agent for the treatment of type 2 diabetes (T2DM). DPP-4i exert their action through potentiation of activity of incretin hormones such as glucagon-like peptide-1 (GLP-1) [1], [2]. However some adverse effects of DPP-4i have been reported and there has been concern about increased risk of pancreatitis and pancreatic cancer [3], [4], [5]. Although studies in a rat model of T2DM showed an adverse effect of DPP-4i on the exocrine pancreas such as ductal metaplasia and pancreatitis [6], more information is needed in humans. The purpose of this study was to determine possible adverse effects of DPP-4i on the exocrine pancreas in patients with T2DM.

Section snippets

Subjects

Twenty four Japanese patients (14 male and 10 female, mean age 61.9 years) with T2DM taking DPP-4i as a first or additional drug were enrolled to the study. HbA1c ranged from 7.0% (53 mmol/mol) – 9.0% (75 mmol/mol) and they had not start taking any new drugs or changed medication within the previous 2 months.

Twelve matched patients (6 male and 6 female, mean age 60.1 years) taking metformin were selected retrospectively as a historical control group. None had severe cardiac, renal, or hepatic

Results

DPP-4i treatment significantly decreased HbA1c from 7.5 ± 0.2% (59 ± 2 mmol/mol) at 0 week to 7.0 ± 0.2% (53 ± 2 mmol/mol) at 8 weeks (p < 0.01). HbA1c lowering was not significantly different between sitagliptin and alogliptin treated subjects (0.6 ± 0.1 and 0.6 ± 0.1%, p = 0.86 at 8 weeks; 0.5 ± 0.2 and 0.7 ± 0.2%, p = 0.50 at 24 weeks). In the metformin group HbA1c improved significantly and similar to the DPP-4i group (from 7.6 ± 0.1%, 60 ± 1 mmol/mol at 0 week to 7.1 ± 0.2%, 54 ± 2 mmol/mol at 8 weeks; p < 0.01). None of the

Discussion

In this study serum pancreatic exocrine enzyme activity increased slightly but significantly during treatment with DPP-4i. Furthermore the change of P-amylase activity related positively with leukocyte number and neutrophil number/percentage and negatively with lymphocyte percentage. These results suggest that DPP-4i potentially cause a low-grade subclinical asymptomatic inflammatory change with the pancreas.

Acute pancreatitis has been raised as a possible adverse effect of DPP-4i but there is

Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgments

We thank SRL Corporation (Tokyo, Japan) and Mr. Yuuta Eiraku for their support of sample analysis, Dr. Koutaro Yokote, Tatsuhiko Tokuyama, Toshitake Tokuyama, Takahiko Tokuyama and all member of B4 Laboratory for useful discussion, and Clinical Research Coordinators of Chiba Medical Center for management of the clinical study.

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