Statin treatment is associated with higher levels of insulin resistance, according to study results published in the Journal of the Endocrine Society.

Although statins may reduce the risk for atherosclerosis and cardiovascular disease, these medications may also decrease insulin secretion and worsen insulin resistance. The goals of the current study were to investigate the association between statin use and insulin resistance using the homeostatic model assessment of insulin resistance (HOMA-IR) in patients without diabetes who participated in the observational Canadian Multicenter Osteoporosis Study (CaMos) at year 10 as well as to explore the association between statin use and abdominal aortic calcification assessed on lateral spine radiographs.

The study cohort included 609 individuals (median age, 71 years; 74% women), of whom 152 were statin users and 457 were nonusers.

Statin users had significantly higher HOMA-IR levels (2.6 [95% CI, 1.9-4.4] vs 1.7 [95% CI, 1-2.9] in nonusers; P <.001). In addition, abdominal aortic calcification scores were also significantly higher in statin users compared with those in nonusers.


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Adjustment for propensity to be on a statin when comparing HOMA-IR and abdominal aortic calcification in statin users and nonstatin users supported the association between statin use and higher levels of HOMA-IR (β=1.52; 95% CI, 1.18-1.95; P <.01). Although HOMA-IR was higher in statin users with and without the propensity score included in the statistical analysis, the association between statin use and higher abdominal aortic calcification was no longer significant when stratified by propensity score.

When the researchers examined the effects of statins based on the hydrophilicity or lipophilicity of the particular drug, the results indicated that compared with nonstatin users, HOMA-IR was higher in patients receiving hydrophilic statins (β=2.29; 95% CI, 1.43-3.68; P <.001) as well as in patients receiving lipophilic statins (β=1.36; 95% CI, 1.04-1.78; P <.05).

The negative effect on insulin resistance has historically been linked to the lipophilicity of statins, but HOMA-IR was significantly higher in hydrophilic statin users compared with lipophilic statin users (β=1.79; 95% CI, 1.15-2.79; P <.05). However, the researchers noted that 73% of hydrophilic statin users in this cohort were receiving rosuvastatin, a high-potency hydrophilic statin that has been linked to the highest risk for type 2 diabetes compared with other statins, which may have explained the discrepancy.

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The researchers acknowledged several study limitations, including the cross-sectional design, potential unobserved or inaccurately measured confounders, missing data on cholesterol levels or statin doses, and a study population limited to community-living individuals.

Based on their results, the researchers concluded that statins “…may have unintended consequences related to glucose homeostasis that could be relevant in healthy aging. In those individuals with risk factors for diabetes, consideration for choosing non-lipophilic statins and avoidance of rosuvastatin and lipophilic statins may provide the intended cardiovascular protection without the increased incidence of insulin resistance.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures

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Reference

Rees-Milton KJ, Norman P, Babiolakis C, et al. Statin use is associated with insulin resistance in participants of the Canadian Multicentre Osteoporosis Study [published online May 15, 2020]. J Endocr Soc. doi:10.1210/jendso/bvaa057