Women Report Higher Rates of Statin-Associated Diabetes, FDA Data Reveals

The findings suggest that biological or social factors may contribute to this disparity, emphasizing the need for future research to explore mechanisms that may explain the sex differences in statin-associated DM risk. Understanding these factors could improve prevention strategies and personalized care for patients taking statins.

"This study provides the first real-world evidence showing a significantly higher rate of statin-associated diabetes mellitus in women compared to men, based on 26 years of reports to the U.S. Food and Drug Administration's national adverse drug event reporting system," the researchers wrote.

Statins have long been recognized as an effective way to lower cholesterol levels and reduce the risk of cardiovascular complications. However, their potential to contribute to the onset of diabetes remains a growing area of research. Secondary analyses of randomized clinical trials and some observational cohort studies have indicated that women may have a higher likelihood than men of developing statin-associated diabetes mellitus. However, no studies using real-world drug safety data to investigate this relationship have been published to date.

Against the above background, David P Kao, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA, and colleagues hypothesized that that statin-associated diabetes mellitus is reported more frequently in women than in men in post-marketing ADE surveillance, highlighting a significant sex difference in the safety profile of this widely prescribed class of medications.

For this purpose, the researchers conducted a retrospective pharmacovigilance analysis of spontaneously reported adverse drug events (ADEs) submitted to the FDA Adverse Event Reporting System from January 1997 through December 2023. They analyzed reports mentioning statins, including atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin collectively, as well as reports for atorvastatin, pravastatin, rosuvastatin, and simvastatin individually.

DM events were identified using the Medical Dictionary for Regulatory Activities (MedDRA). The researchers employed the proportional reporting ratio to determine if statin-associated DM events occurred at higher rates in women and men than other medications. The reporting odds ratio (OR) compared the likelihood of reporting statin-associated DM in women versus men.

The following were the key findings of the study:

• A total of 18,294,814 adverse drug events were reported during the study period.
• Among statin-associated ADEs, 14,874 out of 519,209 (2.9%) reports mentioned diabetes mellitus (DM) in women compared to 7,411 out of 489,453 (1.5%) in men, with both figures significantly higher than the background rate of 0.6%.
• Statins were identified as the primary-suspected or secondary-suspected cause of ADE significantly more often in women (60%) than men (30%).
• Reporting rates for statin-associated DM were disproportionately higher in women than men across all statin types, with a reporting odds ratio (OR) of 1.9.
• The largest gender difference in reporting statin-associated DM was observed with atorvastatin.

The authors found that analysis of post-marketing spontaneous ADE reports showed a higher reporting rate of diabetes mellitus associated with statin use compared to other medications, with women reporting a significantly higher rate than men. They suggest that future research should explore the mechanisms through which statin-associated DM risk may be influenced by sex.

Reference:

David P Kao, James L Martin, Christina L Aquilante, Elise L Shalowitz, Katarina Leyba, Elizabeth Kudron, Jane E B Reusch, Judith G Regensteiner - Sex-differences in reporting of statin-associated diabetes mellitus to the US Food and Drug Administration: BMJ Open Diabetes Research & Care 2024;12:e004343.