Sodium-glucose cotransporter-2 inhibitors and cardiovascular safety profile: a pharmacovigilance analysis of the US food and drug administration adverse event reporting system

ABSTRACT

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are effective in reducing the risk of heart failure (HF) in type 2 diabetic patients. We systematically examined the association between cardiac adverse events (CAEs) and SGLT2i.

Research design and methods

We analyzed CAEs in the FDA Adverse Event Reporting System between January 2013 and March 2021. The CAEs were classified into four major groups according to their preferred terms. Disproportionality and Bayesian analyses were performed to detect signals using reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayesian geometric mean (EBGM). Case seriousness was also described.

Results

There were 2,330 CAEs associated with SGLT2i, and 81 were used for HFs. The SGLT2i were not associated with over-reporting frequencies of CAE based on ROR (ROR = 0.97, 95% confidence interval [CI]: 0.93, 1.01), PRR (PRR = 0.97, 95% CI: 0.94, 1.01), Bayesian confidence propagation neural network (IC = −0.04, IC025: N.A.), and multi-item gamma Poisson shrinker (EBGM = 0.97, EBGM05:0.94), unless further restricted to myocardial infarction (ROR = 2.03, 95% CI = 1.89, 2.17). Additionally, SGLT2i-associated CAEs are associated with 11.33% fatality and 51.25% hospitalization.

Conclusions

SGLT2i present a favorable cardiac safety profile; however, concerns should be raised regarding their potential association with specific events.

KEYWORDS:

• SGLT2 inhibitors
• epidemiology
• observational
• pharmacovigilance
• type 2 diabetes mellitus

Declaration of interests

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 this manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, and royalties.

Reviewer disclosures

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

Author contributions statement

M Cao and D Jiang conceived the study and designed the manuscript. L Zhang and C Pan participated in the data collection process and performed statistical analyses. L Zhang wrote the first draft of the manuscript, and X Yang and M Cao reviewed and modified it. All the authors have read and approved the submitted manuscript.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2023.2216453

Additional information

Funding

This paper was funded by Research Foundation of Beijing Shijitan Hospital Affiliated to Capital Medical University (2022-C03) and the National Natural Science Foundation of China (82004011).