Statin Therapy Initiation and Diabetes Progression

Quick Takes

  • Statin initiation was associated with the progression of diabetes in a large retrospective study of US Veterans who had a diagnosis of diabetes.
  • Statin initiation was associated with the initiation of insulin or increase in the number of glucose-lowering medication prescriptions compared to an active comparator group.
  • Greater episodes of hyperglycemia were identified in the statin group.

Study Questions:

Is statin initiation associated with progression of diabetes among Veterans with diabetes?

Methods:

This was a retrospective matched control study, using data from a large national cohort of Veterans Affairs (VA) patients between 2003 and 2015. Patients who were 30 years or older, diagnosed with diabetes (during the study period), and regular users of the VA health system were included. Patients who initiated statins (during the study period) were matched to an active comparator group, comprising those who initiated H2-blockers or proton pump inhibitors (PPIs) also during the study period. Patients who had filled medications from these classes (statins, H2-blocker, or PPI) in the prior 12 months were excluded. For any patient in the active comparator group who filled a statin prescription during the follow-up period, their follow-up ended as a nonuser (on the date of statin initiation), and they were crossed over to the statin user group (the date of statin initiation became their new index date). The primary outcome of interest was the progression of diabetes defined by a composite outcome of new insulin use, increase in the number of glucose-lowering medication classes, the incidence of ≥5 measurements of blood glucose of ≥200 mg/dl, or a new diagnosis of ketoacidosis or uncontrolled diabetes.

Results:

A total of 83,022 pairs of statin users and matched comparators were identified (mean age 60.1 years, 78,712 [94.9%] were men). The racial/ethnic composition included 1,715 (2.1%) American Indian/Pacific Islander/Alaska Native, 570 (0.8%) Asian, 17,890 (21.5%) Black, and 56,633 (68.2%) white individuals. Diabetes progression outcome occurred in 55.9% of statin users versus 48.0% of active comparators (odds ratio, 1.37; 95% confidence interval, 1.35-1.40; p < 0.001). Each individual component of the composite outcome was significantly higher among statin users. Secondary analysis demonstrated a dose-response relationship with a higher intensity of low-density lipoprotein cholesterol lowering associated with greater diabetes progression.

Conclusions:

The investigators concluded that statin use was associated with diabetes progression, including a greater likelihood of insulin treatment initiation, significant hyperglycemia, acute glycemic complications, and an increased number of prescriptions for glucose-lowering medication classes.

Perspective:

This large retrospective study observed the progression of diabetes, including greater use of insulin and antiglycemic medications among Veterans who initiated statin therapy. Such data, although not from a randomized controlled trial, do support the discussion between a provider and patient as to the risks and benefits for statin use.

Keywords: Blood Glucose, Cholesterol, LDL, Diabetes Mellitus, Dyslipidemias, Glucose, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperglycemia, Insulin, Ketosis, Primary Prevention, Proton Pump Inhibitors, Risk Assessment, Veterans


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