Comprehensive safety profile of dipeptidyl peptidase-4 inhibitors: a post-marketing study based on FAERS database using signal detection algorithms

ABSTRACT

Background

Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) have acquired a foothold in managing type 2 diabetes mellitus, but few concerns have arisen regarding their overall safety profile. The aim of this study is to assess the potential risk of DPP-4 inhibitors by analyzing data from the FDA Adverse Event Reporting System (FAERS) database.

Research design and methods

This is a retrospective study which explored the FAERS database till March 2023 for the collection of safety reports. The disproportionality analysis was performed using signal detection algorithms (SDAs) incorporating frequentist-based data mining approach such as relative reporting ratio (RRR), reporting odds ratio (ROR) and proportional reporting ratio (PRR) with 95% confidence interval (CI).

Results

A total of 14,573 adverse event reports were reported in the FAERS public dashboard associated with all the included DPP-4 inhibitors. The computed PRR, ROR, and RRR indicated positive signals for DPP-4 inhibitors with cardiac failure, pancreatitis, pemphigoid, hypoglycemia, acute kidney injury and lactic acidosis. Saxagliptin showed a higher signal score for cardiac failure, while sitagliptin was more associated with pancreatitis. Moreover, alogliptin exhibited an elevated signal score associated with pancreatic carcinoma.

Conclusion

Several significant disproportionality signals were observed with DPP-4 inhibitors. However, clinicians have to consider the comorbidities and concomitant drugs while prescribing these drugs.

KEYWORDS:

• Dipeptidyl peptidase-4 inhibitors
• signal detection
• signal detection algorithms
• type 2 diabetes mellitus
• pharmacovigilance

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

B.T. Yoosuf conceptualized the study framework, compilation of the data, and drafted the manuscript; M. Favas KT analyzed and interpreted the data, cross-checked the information; D, Bansal and P. Dutta critically evaluated the final draft of the review of manuscript. All authors participated in the manuscript review process and endorsed the final version.

Acknowledgments

We extend our gratitude to our colleagues at the National Institute of Pharmaceutical Education and Research (NIPER) S.A.S. Nagar for their valuable insights and expertise, which significantly contributed to our research.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2024.2343015

Additional information

Funding

This paper was funded by financial support received from Indian Council of Medical Research (ICMR) extramural grant.