Does statin (HMG-CoA reductase inhibitor) therapy cause insulin resistance in postmenopausal women?

From the Guidelines

Statin therapy may increase the risk of insulin resistance and type 2 diabetes in postmenopausal women, but the absolute risk is small and outweighed by the cardiovascular benefits of statins. Several studies suggest that commonly prescribed statins like atorvastatin, rosuvastatin, and simvastatin can modestly increase fasting blood glucose levels and hemoglobin A1c in postmenopausal women, who are already at higher diabetes risk due to age-related and estrogen-deficiency metabolic changes 1. The mechanism appears to involve statins reducing insulin sensitivity in muscle tissue and potentially impairing pancreatic beta-cell function.

Key points to consider:

• The JUPITER trial found that women taking rosuvastatin had a small but significant increase in HbA1c compared with placebo, and a greater risk of developing new diabetes 1.
• The Women's Health Initiative reported that statin use was associated with an increased risk of self-reported new-onset diabetes in postmenopausal women, but the absolute risk was small, with one case of incident diabetes for every 1000 women taking statins per year 1.
• The guidelines indicate that high-intensity statins are associated with an incidence of diabetes of 0.3 per 100 persons treated, compared to 0.1 per 100 in those without statin treatment 1.
• A recent analysis of the Dallas Heart Study demonstrated that statin-related CVD event reduction far outweighs the elevated diabetes risk 1.

In terms of management, postmenopausal women taking statins should have their blood glucose monitored regularly, particularly in the first year of treatment. Those with prediabetes or other diabetes risk factors should be especially vigilant. Lifestyle modifications including regular exercise, maintaining healthy weight, and following a balanced diet remain important for minimizing this risk while on statin therapy. The 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults also supports the use of statins in primary and secondary prevention, with a focus on individualized risk assessment and treatment goals 1.

From the Research

Statin Use and Insulin Resistance in Postmenopausal Women

• The relationship between statin use and insulin resistance in postmenopausal women is complex and has been studied in various research papers 2, 3, 4, 5, 6.
• A study published in 2012 found that postmenopausal women with type 2 diabetes who were on statin therapy had improved insulin sensitivity and reduced estimated 10-year cardiovascular disease risk after consuming flavan-3-ols and isoflavones for 1 year 2.
• However, another study published in 2013 suggested that statins may be associated with an increased risk of developing type 2 diabetes, possibly by accelerating progression to diabetes via molecular mechanisms that impact insulin resistance and cellular metabolism of carbohydrates 3.
• A 2015 cohort study found that insulin resistance measures did not improve cardiovascular disease risk discrimination and reclassification in postmenopausal women without diabetes mellitus, and that high-density lipoprotein-cholesterol was a stronger predictor of cardiovascular disease risk 4.
• A 2021 clinical trial found that atorvastatin increased insulin resistance and insulin secretion in adults without known atherosclerotic cardiovascular disease or type 2 diabetes at baseline, suggesting that statin treatment may increase the risk of type 2 diabetes in individuals who become more insulin resistant but are unable to maintain compensatory increases in insulin secretion 5.
• Another study published in 2008 found that hormone replacement therapy and coffee consumption may have concurrent effects on insulin resistance in postmenopausal women, with the combination of coffee consumption and hormone replacement therapy potentially lowering insulin resistance in postmenopausal women 6.

Key Findings

• Statin use may be associated with an increased risk of developing type 2 diabetes in postmenopausal women 3, 5.
• Insulin resistance measures may not improve cardiovascular disease risk discrimination and reclassification in postmenopausal women without diabetes mellitus 4.
• Hormone replacement therapy and coffee consumption may have concurrent effects on insulin resistance in postmenopausal women 6.
• Flavan-3-ols and isoflavones may improve insulin sensitivity and reduce estimated 10-year cardiovascular disease risk in postmenopausal women with type 2 diabetes who are on statin therapy 2.