Abstract

Background Glucose metabolism disorders encompass abnormalities in glucose digestion, absorption, transport, utilization, and regulation, leading to broad physiological and pathological consequences. Although drug-induced disturbances are increasingly documented, they remain under-recognized in clinical practice and drug labeling.

Methods This disproportionality analysis used publicly available data from the FDA Adverse Event Reporting System (FAERS), covering reports from Q4 2004 to Q1 2025. After data cleaning and standardization, four disproportionality methods (ROR, PRR, MGPS, BCPNN) were applied to detect signals. A signal was considered positive only if all method thresholds were met (ROR: n ≥ 3, lower 95% CI > 1; PRR: χ² ≥ 4, lower 95% CI > 1; MGPS: EBGM05 > 2; BCPNN: IC025 > 0). A descriptive analysis of clinical characteristics and a case-by-case assessment were also performed.

Results Among 22,775,812 reports, 204,236 were related to glucose metabolism disorders and involved 1,827 drugs. A total of 128 drugs showed positive signals. The most frequent classes were anti-diabetic drugs (38%), antineoplastic agents (9.3%), renin-angiotensin system drugs (8.6%), and systemic corticosteroids (4.7%). Notably, several drugs, including basiliximab, enfortumab vedotin, and mercaptopurine, lack explicit warnings regarding glucose metabolism disorders.

Conclusion This study identifies potential safety signals that require further clinical validation. These findings emphasize the need for improved monitoring and timely updates to drug labeling, particularly for high-risk populations. Disproportionality analysis is hypothesis-generating and should be interpreted with caution.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Yes

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study conducted a retrospective observational analysis utilizing the public database of the US FDA Adverse Event Reporting System. All data within this database have undergone rigorous anonymization processes and do not contain any personally identifiable information, making it a publicly accessible scientific resource. In accordance with the exemption clause for the secondary use of public databases as outlined in international ethical guidelines, this study did not involve individual intervention or harm therefore, it did not require review by an ethics review committee.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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AbbreviationsACTHAdrenocorticotropic HormoneAEsAdverse EventsAKTProtein Kinase BATCAnatomical Therapeutic ChemicalBCPNNBayesian Confidence Propagation Neural NetworkcAMPCyclic Adenosine MonophosphateEBGMEmpirical Bayes Geometric MeanFAERSFDA Adverse Event Reporting SystemGLP-1Glucagon-like Peptide-1HLTHigh-Level TermIC025Information Component 025ICIsImmune Checkpoint InhibitorsMGPSMulti-item Gamma Poisson ShrinkerMedDRAMedical Dictionary for Regulatory ActivitiesmTORMammalian Target of RapamycinPI3KPhosphatidylinositol 3-kinasePRRProportional Reporting RatioPSPrimary Suspected DrugPTPreferred TermRORReporting Odds RatioSSTR5Somatostatin Receptor 5T1DMType 1 Diabetes MellitusT2DMType 2 Diabetes Mellitus