Adverse event profiles of dipeptidyl peptidase-4 inhibitors: data mining of the public version of the FDA adverse event reporting system

Jing Huang,Shusen Sun,Long Meng,Yuntao Jia

doi:10.1186/s40360-020-00447-w

Abstract

BackgroundTo describe and analyze the patterns of adverse events associated with dipeptidyl peptidase-4 inhibitors (DPP-4is) (sitagliptin, saxagliptin, linagliptin, vildagliptin, and alogliptin) from the FDA Adverse Event Reporting System (FAERS) and to highlight areas of safety concerns.MethodsAdverse events spontaneously submitted to the FAERS between 2004 Q1 to 2019 Q2 were included. The online tool OpenVigil 2.1 was used to query the database. The research relied on definitions of preferred terms (PTs) specified by the Medical Dictionary for Regulatory Activities (MedDRA) and the standardized MedDRA Queries (SMQ). The reporting odds ratio (ROR), with 95% confidence intervals (CIs) was calculated for disproportionality analysis.ResultsOver 16 years, a total of 9706 adverse event reports were identified. Alogliptin was excluded from further analysis due to insufficient sample size. Compared with the non-insulin antidiabetic drugs, the four DPP-4is were all disproportionately associated with four SMQs: “gastrointestinal nonspecific inflammation and dysfunctional conditions,” “hypersensitivity,” “severe cutaneous adverse reactions,” and “noninfectious diarrhoea”. As for PT level analyses, DPP-4is are associated with higher reporting of the gastrointestinal tract, pancreas, malignancies, infection, musculoskeletal disorders, general disorders, hypersensitivity, and skin AEs.ConclusionsData mining of the FAERS is useful for examining DPP-4 inhibitors-associated adverse events. The findings of the present study are compatible with clinical experience, and it provides valuable information to decision-makers and healthcare providers in clinical practice.

Highlights

To describe and analyze the patterns of adverse events associated with dipeptidyl peptidase-4 inhibitors (DPP-4is) from the FDA Adverse Event Reporting System (FAERS) and to highlight areas of safety concerns
Because the total number of adverse events occurring with alogliptin was not large enough to compare the association with adverse events of the other four DPP-4is, alogliptin was excluded from further analysis [4]
Considering DPP-4is as a class, signals of disproportionate reporting (SDR) emerged in 13 standardized MedDRA Queries (SMQ): “gastrointestinal nonspecific inflammation and dysfunctional conditions”, “hypersensitivity”, “acute pancreatitis”, “haemodynamic oedema, effusions and fluid overload”, “malignancies”, “noninfectious diarrhoea”, “angioedema”, “hepatic disorders”, “arthritis”, “gastrointestinal perforation, ulceration, haemorrhage or obstruction”, “severe cutaneous adverse reactions”, “taste and smell disorders” and “anaphylactic reaction”

Summary

Introduction

To describe and analyze the patterns of adverse events associated with dipeptidyl peptidase-4 inhibitors (DPP-4is) (sitagliptin, saxagliptin, linagliptin, vildagliptin, and alogliptin) from the FDA Adverse Event Reporting System (FAERS) and to highlight areas of safety concerns. Oral agents are the mainstay of pharmacological treatment for T2DM. Dipeptidyl peptidase-4 inhibitors (DPP-4is) are a valuable addition to the antidiabetic treatment modalities and have been widely used [1]. DPP-4is, sitagliptin, saxagliptin, linagliptin, vildagliptin, and alogliptin, have significantly different chemical structures, leading to differences in their pharmacokinetic and pharmacodynamic properties. It is not entirely clear if these differences may result in differing safety profiles [2]. It is necessary to explore adverse events (AEs) induced by DPP-4is in a real-world environment

Methods

Results

Discussion

Conclusion