Statin Use Associated with Increased Odds of Worsening Diabetes, Study Finds

Using data from more than 80k matched pairs of statin users and comparators, investigators from UT Southwestern Medical Center found initiation of statin therapy was associated with an increased likelihood of diabetes progression, including risk of hyperglycemia and ketoacidosis.

Data from a matched-cohort study indicates statin use was associated increased odds of worsening diabetes in a national cohort of patients with type 2 diabetes.

Results of the study, which included data from 83,022 matched pairs of statin users and comparators, indicate statin initiation was associated with increased risk of diabetes progression, including an increase in the likelihood of initiating new therapies and experiencing glycemic events.

“The higher risk of diabetes progression associated with statin use may seem less consequential, at least in the short and intermediate term, than the cardiovascular benefits of statin use, especially when used for secondary prevention,” wrote investigators. “However, diabetes progression has long-term effects on quality of life and treatment burden, which warrant consideration when discussing the overall risk-benefit profile, especially when used for primary prevention.”

To further investigate potential links between statin therapy and increased insulin resistance, a team of investigators from the University of Texas Southwestern Medical Center conducted the current study with the intent of using data from the national Veterans Affairs Corporate DataWarehouse from 2003-2015. Using a validated algorithm, investigators sought to identify all patients with VA medical encounters and a diagnosis of diabetes from the aforementioned period and assess whether initiation of statin therapy was associated with progression of diabetes, which was defined as a composite of new insulin initiation, increase in the number of glucose-lowering medication classes, incidence of 5 or more measurements of blood glucose of 200 mg/dL or greater, or a new diagnosis of ketoacidosis or uncontrolled diabetes.

For inclusion in the study, patients needed to be at least 30 years of age or older, have at least 1 VA encounter, blood pressure and weight measurements, VA pharmacy dispensing data, and laboratory data, including g blood or serum glucose, creatinine, and LDL-C measurements. Investigators planned a total of 6 primary and secondary analyses, including analyses stratifying patients by presence of comorbidities and intensity of statin therapy. Of note, the exposure of interest for the study was treatment initiation with statins for those classified as statin users and treatment initiation with H2-blockers or portion pump inhibitors for those classified as comparators.

The investigators identified a cohort of 705,774 VA patients considered eligible for inclusion in the study, including 595,579 statin users. From this cohort, investigators identified 83,022 matched pairs of statin users and active comparators. This cohort had a mean age of 60.1 (SD, 11.6) years, 94.9% were men, and 68.2% were White.

Results of the investigators' analyses suggested statin users had significantly greater odds of diabetes progression compared with nonusers, with increased odds observed for increases in the number of glucose-lowering medication classes (OR, 1.41; 95% CI, 1.38- 1.43), new insulin starts (OR, 1.16; 95% CI, 1.12-1.19), presence of persistent hyperglycemia (OR, 1.13; 95% CI, 1.10-1.16), and new diagnosis of ketoacidosis or uncontrolled diabetes (OR, 1.24; 95% CI, 1.19-1.30).

Secondary analyses provided further insight into the potential effects of statin therapy on diabetes progression, with all secondary and sensitivity analyses indicating the odds of diabetes progression were consistently greater among statin users compared to nonusers. Investigators highlighted analyses demonstrating odds of diabetes progression were greater among statin users with no other comorbidities compared to the overall cohort and demonstrating more intensive cholesterol-lowering therapy was associated with the greatest odds of diabetes progression among statin users compared with nonusers.

“This metabolic cost was not considered in RCTs of statins. Further research is needed to form a risk-tailored approach to balancing the cardiovascular benefits of statin therapy with its risk of diabetes progression,” wrote investigators.

This study, “Association of Statin Therapy Initiation With Diabetes Progression,” was published in JAMA Internal Medicine.