Using electronic medical record data from Veterans Affairs, the researchers found that statin use was associated with a greater risk of diabetes progression.
Results of a retrospective study linking statin use to diabetes progression; In particular, the researchers explained that the odds of starting insulin therapy are higher for significant hyperglycemia, acute glycemic complications, and an increasing number of prescriptions for the glucose-lowering drug classes. Findings published JAMA Internal Medicine.
While guidelines recommend statin therapy for all patients with type 2 diabetes aged 40 to 75 years with low-density lipoprotein (LDL) cholesterol levels of 70 mg/dL or higher, research has shown that use of the drug class is associated with increased insulin resistance, and the authors further high blood sugar levels, he said.
Statins are primarily prescribed to help prevent cardiovascular disease (CVD) in this population. However, increased insulin resistance can accelerate the progression of diabetes and subsequently increase the risk of CVD.
To better understand how statin use affects glycemic control, the researchers compared diabetes progression in patients following statin initiation with that in patients not using statins. The retrospective matched cohort study included patients under the U.S. Department of Veterans Affairs (VA) between fiscal years 2003 and 2015.
While medical record data was collected from the national VA Corporate Data Warehouse, only individuals 30 years of age and older at the date of the index were included in the analysis. Non-statin users included in the analysis started either H2-blockers (H2) or proton pump inhibitors (PPI) (these were active comparators) during the study window.
The matched cohort comprised a total of 83,022 pairs of statin users and active comparators. 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 onset of insulin, increase in the number of glucose-lowering drug classes, 5 or more incidences of blood glucose readings of 200 mg/dL or higher, or a new ketoacidosis or uncontrolled diagnosis.” diabetes.”
Their analysis revealed that:
- Diabetes progression outcome occurred in 55.9% of statin users and 48% of active comparators (odds ratio). [OR], 1.37; 95% CI, 1.35-1.40; P < .001)
- A significantly higher proportion of each component of diabetes progression outcome was found in statin users compared to nonusers:
- Increase in the number of glucose-lowering drug 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, the authors wrote, “There was a dose-response relationship between the intensity of lowering LDL cholesterol and the risk of study outcomes, associated with higher LDL cholesterol density and a higher probability of diabetes progression.” “For example, the odds of diabetes progression among statin users and nonusers were 1.83, 1.55, and 1.45 for high, moderate- and low-intensity cholesterol lowering, respectively.”
In the short and near term, the high risk of diabetes progression associated with statin use may outweigh the cardiovascular benefits of statin use. However, the researchers explained that the long-term effects of diabetes progression on quality of life and treatment burden need to be considered when providers weigh the risk-benefit profile of statins.
From the available data, the researchers were unable to determine whether 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 pointed to a limitation for the current study.
The results showed, overall, that “statin use is associated with a higher risk of escalation and increased risk of hyperglycemic complications of diabetes treatment,” the authors concluded, a metabolic cost that was not considered in randomized controlled trials of statins. “More research is needed to establish a risk-adapted approach to balance the cardiovascular benefits of statin therapy with the risk of diabetes progression,” they said.
Mansi IA, Chansard M, Lingvay I, Zhang S, Halm EA, Alvarez CA. Association of starting statin therapy with diabetes progression: a retrospective matched cohort study. JAMA Intern Med.Released online on October 4, 2021. doi:10.1001/jamainternmed.2021.5714