Study Finds Statin Use Associated With Diabetes Progression

Results of a retrospective study linked statin use to diabetes progression; specifically, a greater likelihood of insulin treatment initiation, significant hyperglycemia, acute glycemic complications, and an increased number of prescriptions for glucose-lowering medication classes, researchers explained. Findings were published in JAMA Internal Medicine.

Although guidelines recommend statin therapy for all patients with type 2 diabetes aged 40 to 75 who have low-density lipoprotein (LDL) cholesterol levels of 70 mg/dL or greater, research shows the medication class' use has been associated with increased insulin resistance and higher blood glucose levels, the authors said.

Statins are primarily prescribed in this population to help prevent cardiovascular diseases (CVD). However, increased insulin resistance could fuel diabetes progression and subsequently increase the risk of CVD.

To better understand how statin use affects glycemic control, the investigators compared diabetes progression in patients following statin initiation to that of patients who did not use statins. The retrospective matched-cohort study included patients covered by the US Department of Veterans Affairs (VA) between fiscal years 2003 and 2015.

Medical record data were gleaned from the national VA Corporate Data Warehouse, while only individuals aged 30 or over at the index date were included in the analysis. Nonstatin users included in the analysis initiated H2-blockers (H2) or proton pump inhibitors (PPI)—these were the active comparators—throughout the study window.

A total of 83,022 pairs of statin users and active comparators made up the matched cohort. The mean (SD) patient age was 60.1 (11.6) years and the majority (94.9%) were male.

The researchers defined the diabetes progression composite outcome as “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.”

Their analyses revealed:

• Diabetes progression outcome occurred in 55.9% of statin users vs 48% of active comparators (odds ratio [OR], 1.37; 95% CI, 1.35-1.40; P < .001)
• A significantly higher rate of each component of the diabetes progression outcome in statin users compared with nonusers was found:
  • Increase 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)
  • New diagnosis of ketoacidosis or uncontrolled diabetes (OR, 1.24; 95% CI, 1.19-1.30)

In addition, “there was a dose-response association between intensity of lowering LDL cholesterol and risk of the study outcomes, with higher intensity of LDL cholesterol–lowering associated with higher odds of diabetes progression,” the authors wrote. “For example, the odds of diabetes progression among statin users vs nonusers were 1.83, 1.55, and 1.45 for high-, moderate-, and low-intensity cholesterol lowering, respectively.”

In the short and immediate term, the higher risk of diabetes progression linked with statin use may be less consequential than the cardiovascular benefits of statin use. However, the long-term effects of diabetes progression on quality of life and treatment burden warrant consideration when providers weigh the risk-benefit profile of statins, the researchers explained.

From the available data, the investigators could not determine if the association of statin use with diabetes progression was due to statin use or lower LDL cholesterol, as statins are inseparable from their cholesterol-lowering effects. This marked a limitation to the current study.

Overall, the results showed, “statin use was associated with a higher risk of diabetes treatment escalation and an increased risk of hyperglycemic complications,” the authors concluded, a metabolic cost not considered in randomized controlled trials 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,” they said.

Reference:

Mansi IA, Chansard M, Lingvay I, Zhang S, Halm EA, Alvarez CA. Association of statin therapy initiation with diabetes progression: a retrospective matched-cohort study. JAMA Intern Med. Published online October 4, 2021. doi:10.1001/jamainternmed.2021.5714