How do HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, also known as statins, influence glycemic control?

From the Guidelines

Statins can negatively impact glycemic control by increasing insulin resistance and reducing insulin secretion, as evidenced by a small increase in glycaemia, which translates into a moderate increase in the rate at which individuals are diagnosed with new-onset diabetes or worsening glycaemic control among those with diabetes 1. The mechanism involves interference with glucose transporters, impaired insulin signaling pathways, and reduced pancreatic beta-cell function. Higher-potency statins like atorvastatin and rosuvastatin typically have more pronounced effects on glucose metabolism than lower-potency options like pravastatin. Some key points to consider:

• The mean changes in glycaemia are small, with a moderate dose-dependent increase in new diagnoses of diabetes, particularly among individuals who are already at high risk of diabetes 1.
• The relative effects on worsening glycaemic control in people with known diabetes largely mirrored those for new-onset diabetes, with a small increase in blood glycaemia within a few months of starting treatment.
• Despite these effects, the cardiovascular benefits of statins generally outweigh the modest impact on glycemic control for most patients with diabetes or cardiovascular risk factors.
• Patients taking statins should have their blood glucose monitored regularly, particularly when initiating therapy or changing doses, and those with prediabetes or at high risk for developing diabetes may need more frequent monitoring 1.
• Lifestyle modifications, including regular physical activity and a healthy diet, remain important for mitigating potential glycemic effects while on statin therapy. Key considerations for clinical practice:
• Regular monitoring of blood glucose levels, especially in high-risk patients
• Lifestyle modifications to mitigate potential glycemic effects
• Weighing the cardiovascular benefits of statins against the potential impact on glycemic control.

From the Research

Statins and Glycemic Control

• Statins are known to have varying effects on glucose metabolism, with some studies suggesting that certain statins may impair glycemic control, while others may have a neutral or even beneficial effect 2, 3, 4, 5, 6.
• The diabetogenic effect of statins may be influenced by factors such as lipophilicity, with lipophilic statins like atorvastatin and simvastatin potentially having a greater adverse impact on glucose metabolism compared to hydrophilic statins like pravastatin and pitavastatin 3.
• Studies have shown that pitavastatin may have a more favorable effect on glycemic control compared to other statins, with moderate-intensity pitavastatin lowering HbA1c levels and improving fasting plasma glucose (FPG) compared to atorvastatin, rosuvastatin, and simvastatin 4, 5.
• High-intensity atorvastatin, on the other hand, has been associated with worsening glycemic control, with increased HbA1c and FPG levels compared to placebo and other statins 4, 6.
• The mechanisms by which statins influence glucose metabolism are complex and may involve effects on pancreatic islet blood flow, adipokine levels, and insulin sensitivity, among other factors 3, 5.

Comparison of Statins

• Pravastatin has been shown to have a beneficial effect on glucose metabolism, with improved glycemic control and reduced risk of diabetes 3.
• Rosuvastatin has been associated with a neutral or slightly adverse effect on glycemic control, although the evidence is mixed 3, 4, 5.
• Simvastatin has been linked to impaired glucose metabolism, particularly at high doses, although some studies suggest that it may have a neutral effect on glycemic control 2, 3, 4.
• Pitavastatin has been shown to have a favorable effect on glycemic control, with improved HbA1c and FPG levels compared to other statins 4, 5.

Clinical Implications

• The choice of statin may be important in patients with diabetes or prediabetes, with consideration given to the potential impact on glycemic control 2, 3, 4, 5, 6.
• Clinicians should be aware of the potential for statins to influence glucose metabolism and monitor patients accordingly, particularly when initiating or adjusting statin therapy 2, 3, 4, 5, 6.