Pneumatosis intestinalis associated with α-glucosidase inhibitors: a pharmacovigilance study of the FDA adverse event reporting system from 2004 to 2022

ABSTRACT

Background

A-glucosidase inhibitors (AGIs) are suitable for type 2 diabetes mellitus patients with carbohydrate-rich diets while were reported associated with the rare but potentially life-threatening pneumatosis intestinalis (PI).

Research design and methods

Data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) were examined for AGIs, acarbose, voglibose, miglitol, or other anti-hyperglycemic drug classes. The reporting odds ratio (ROR), proportional reporting ratio, gamma poisson shrinker, and bayesian confidence propagation neural network were applied to determine the safety signals, which were performed under two other models to control for bias from type 2 diabetes mellitus and other anti-hyperglycemic drugs.

Results

We found a significantly higher reporting of PI in all AGIs group [ROR = 73.85 (61.56–88.58)]. When further subdivided, voglibose and miglitol had a larger ROR than acarbose whether models were adjusted or not. The safety signals of biguanides, sulfonylureas, thiazolidinediones, dipeptidyl peptidase 4 inhibitors inhibitors, glucagon-like peptide-1 receptor agonists, sodium-glucose co-transporter-2 inhibitors, and other drug classes were not detected in three models.

Conclusions

Our study identified the safety signals of the PI-AGIs pair, primarily based on disproportionality analysis while controlling for confounders such as the disease-associated risk of PI and concomitant drug exposure.

KEYWORDS:

• FAERS
• disproportionality analysis
• pharmacovigilance
• Pneumatosis intestinalis
• α-glucosidase inhibitors

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

Reviewer disclosures

One reviewer has received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Pharmaserve Lilly, and Novo Nordisk, for advisory boards from Novo Nordisk and Boehringer Ingelheim, and has participated in sponsored studies by Eli-Lilly and Novo Nordisk. The remaining reviewers have no other relevant financial relationships or otherwise to disclose.

Author contribution statement

All authors contributed to the writing and editing of this paper. Yiqian Chen, Jun Yi, and Xiaowei Liu designed the study. Yiqian Chen and Yao Xiao performed all analyses. Yiqian Chen write the manuscript. All authors read and approved the final version submitted for publication.

Data availability statement

The original data could be obtained from FAERS (https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html). This manuscript has data included as electronic supplementary materials.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2023.2278708

Additional information

Funding

This paper was funded by the National Natural Science Foundation of China (Grant number 82000502 and 82170599) and China Postdoctoral Science Foundation (Grant number 2021M693572).