Can HMG-CoA reductase inhibitors (statins) contribute to the development of insulin resistance in postmenopausal women?

From the Guidelines

Statins may increase the risk of insulin resistance in postmenopausal women, particularly with high-intensity statin therapy, as evidenced by the JUPITER trial which showed a small but significant increase in HbA1c in women taking rosuvastatin compared to placebo 1. The relationship between statins and insulin resistance is complex, and the risk appears to be dose-dependent, with higher doses carrying greater risk. Postmenopausal women may be particularly vulnerable due to already experiencing metabolic changes associated with estrogen decline. Some key points to consider include:

• The Women's Health Initiative found an increased risk of self-reported new-onset diabetes in postmenopausal women taking statins, with a hazard ratio of 1.48 and an absolute risk rate of one case of incident diabetes for every 1000 women taking statins per year 1.
• The guidelines recommend screening for new-onset diabetes in patients on statin therapy, but also note that the ASCVD risk reduction benefit outweighs the excess potential risk of diabetes 1.
• Lifestyle modifications, including regular exercise and a healthy diet, can help mitigate potential insulin resistance effects, and should be part of the therapeutic plan for postmenopausal women on statin therapy 1.
• The choice of statin and dosage should be individualized, taking into account the patient's cardiovascular risk factors and potential risk of insulin resistance, and the healthcare provider may consider adjusting the statin type or dosage if insulin resistance develops. It's essential to weigh the potential benefits of statin therapy against the risks and to monitor patients closely for signs of insulin resistance or diabetes. Regular monitoring of blood glucose levels and lifestyle modifications can help mitigate potential insulin resistance effects.

From the FDA Drug Label

Increases in HbA1c and fasting serum glucose levels have been reported with statins, including atorvastatin. The FDA drug label does not specifically address whether statins can cause insulin resistance in postmenopausal women. However, it does mention that increases in HbA1c and fasting serum glucose levels have been reported with statins, including atorvastatin 2. This suggests that statins may have an effect on glucose metabolism, but it does not provide direct evidence of insulin resistance in postmenopausal women.

• Key points:
  • Increases in HbA1c and fasting serum glucose levels have been reported with statins.
  • The FDA drug label does not specifically address insulin resistance in postmenopausal women.
  • Optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices, as mentioned in the label 2.

From the Research

Statins and Insulin Resistance in Postmenopausal Women

• The relationship between statin use and insulin resistance in postmenopausal women has been investigated in several studies 3, 4.
• A narrative review found that statin use is associated with an increased risk of new-onset type 2 diabetes in postmenopausal women, with factors such as the type and dose of statin and baseline metabolic status influencing this association 3.
• A clinical trial found that atorvastatin increased insulin resistance and insulin secretion in adults without known atherosclerotic cardiovascular disease or type 2 diabetes at baseline 4.
• Another study found that insulin resistance measures, such as fasting serum insulin and HOMA-IR, were associated with increased cardiovascular disease risk in postmenopausal women, but this association was no longer significant after adjusting for high-density lipoprotein-cholesterol 5.

Mechanisms and Factors Influencing Insulin Resistance

• The physiological mechanism for the increased type 2 diabetes risk associated with statin use is thought to involve increased insulin resistance and secretion 4.
• Factors such as body mass index, age, and blood pressure may influence insulin resistance in postmenopausal women, with hypertensive women having a slightly higher body mass index but the same degree of insulin resistance as normotensive women 6.
• Hormone replacement therapy (HRT) and coffee consumption may also have concurrent effects on insulin resistance in postmenopausal women, with HRT associated with lower insulin resistance and coffee use associated with a decrease in insulin resistance in non-obese women receiving HRT 6.

Clinical Implications

• The findings of these studies suggest that statin use may be associated with an increased risk of insulin resistance and type 2 diabetes in postmenopausal women, particularly in those with pre-existing insulin resistance or prediabetes 3, 4.
• Clinicians should consider the potential benefits and risks of statin therapy in postmenopausal women, taking into account individual factors such as metabolic status and cardiovascular risk 3.
• Further research is needed to fully understand the relationship between statin use and insulin resistance in postmenopausal women, and to inform clinical decision-making in this population 7, 3.