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. 2024 Dec 5;12(6):e004343.
doi: 10.1136/bmjdrc-2024-004343.

Sex-differences in reporting of statin-associated diabetes mellitus to the US Food and Drug Administration

David P Kao  1   2   3 , James L Martin  4   5 , Christina L Aquilante  4   5 , Elise L Shalowitz  4 , Katarina Leyba  3 , Elizabeth Kudron  4   6 , Jane E B Reusch  2   3 , Judith G Regensteiner  2   3   6
Affiliations

Sex-differences in reporting of statin-associated diabetes mellitus to the US Food and Drug Administration

David P Kao et al. BMJ Open Diabetes Res Care. .

Abstract

Introduction: Diabetes mellitus (DM) is increasingly recognized as a possible consequence of statin therapy. Secondary analysis of randomized clinical trials and limited observational cohort analyses have suggested that women may be more likely than men to experience statin-associated DM. No analyses of real-world drug safety data addressing this question have been published.

Research design and methods: This was a retrospective pharmacovigilance analysis of spontaneously reported adverse drug events (ADEs) submitted to the Food and Drug Administration Adverse Event Reporting System between January 1997 through December 2023. We analyzed cases that mentioned atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin in aggregate as well as cases reporting atorvastatin, pravastatin, rosuvastatin, simvastatin individually. DM events were identified using the Medical Dictionary for Regulatory Activities. We used the proportional reporting ratio to identify increased rates of statin-associated DM events in women and men compared with all other medications, and the reporting OR to compare reporting rates in women versus men.

Results: A total of 18,294,814 ADEs were reported during the study period. Among statin-associated ADEs, 14,874/519,209 (2.9%) reports mentioned DM in women compared with 7,411/489,453 (1.5%) in men, which were both significantly higher than background (0.6%). Statins were the primary-suspected or secondary-suspected cause of the ADE significantly more often in women than men (60 vs 30%), and reporting rates were disproportionately higher in women than in men for all statins. (reporting OR 1.9 (95% CI 1.9 to 2.0)). The largest difference in reporting of statin-associated DM between women and women was observed with atorvastatin.

Conclusions: Analysis of post-marketing spontaneous ADE reports demonstrated a higher reporting rate of DM-associated with statin use compared with other medications with a significantly higher reporting rate in women compared with men. Future studies should consider mechanisms of statin-associated DM moderated by sex.

Keywords: Drug-Related Side Effects and Adverse Reactions; Hypercholesterolemia; Medical Informatics Computing; Women's Health.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1. Total unique statin cases in Food and Drug Administration’s Adverse Event Reporting System, January 1, 1997, to December 31, 2023.
Figure 2
Figure 2. (a) Sex-specific proportional reporting ratio for statin-associated DM. (b) Statin-specific proportional reporting ratio for DM by sex. DM, diabetes mellitus.
Figure 3
Figure 3. Countries with published evidence of statin underutilization in women compared with men (see online supplement for references).
See this image and copyright information in PMC

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