Can statins (HMG-CoA reductase inhibitors) increase blood sugar levels?

From the Guidelines

Yes, statins can increase blood sugar levels in some people, as evidenced by a moderate dose-dependent increase in new diagnoses of diabetes and worsening glycaemia, particularly in individuals already at high risk of diabetes. This is supported by a recent individual participant data meta-analysis published in The Lancet Diabetes and Endocrinology 1, which found that statin therapy causes a small increase in glycaemia, translating into a moderate increase in the rate of new-onset diabetes diagnoses. The study also noted that the relative effects on worsening glycaemic control in people with known diabetes largely mirrored those for new-onset diabetes.

Key points to consider:

• The increase in blood sugar levels appears to be dose-dependent, with higher doses carrying greater risk 1.
• Statins interfere with insulin secretion and insulin sensitivity, particularly by affecting glucose transporters in muscle and fat cells.
• Despite this side effect, the cardiovascular benefits of statins typically outweigh the diabetes risk for most patients who need them for cholesterol management 1.
• Regular monitoring of blood glucose levels is recommended, especially if you have prediabetes or other diabetes risk factors.
• Lifestyle modifications like regular exercise and a healthy diet can help counteract potential blood sugar elevations while on statin therapy.
• Patients should not discontinue their statin medication without consulting their healthcare provider, as the overall benefit-risk profile remains favorable for those with appropriate indications 1.

It is essential to weigh the benefits of statin therapy against the potential risks, including the increased risk of developing type 2 diabetes, and to closely monitor patients who are at high risk of diabetes or have already developed it.

From the FDA Drug Label

Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including atorvastatin calcium. Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including simvastatin.

Statins and Blood Sugar Levels:

• Key Finding: Statins, including atorvastatin and simvastatin, have been associated with increases in HbA1c and fasting serum glucose levels.
• Clinical Implication: This suggests that statins may increase blood sugar levels in some patients.
• Precaution: Patients taking statins should be monitored for changes in blood sugar levels, especially those with diabetes or at risk of developing diabetes 2, 3.

From the Research

Statins and Blood Sugar Levels

• Statins, also known as HMG-CoA reductase inhibitors, have been found to increase the risk of diabetes mellitus and worsen glycemic control in patients who already have diabetes 4.
• The association between statin use and increased blood sugar levels is clear, but the mechanisms of action are not fully understood, and causality cannot be established 4.
• Studies have shown that the annual risk of developing new-onset diabetes with statin treatment is approximately 0.1%, while the absolute risk reduction of major coronary events with statin use is approximately 0.42% annually 5.

Mechanisms of Statin-Associated Diabetes Risk

• Multiple mechanisms have been proposed for statin-associated diabetes risk, including increased insulin resistance or impaired insulin secretion 6.
• High-intensity statins, such as atorvastatin 80mg and rosuvastatin 20mg, are associated with a higher excess risk of diabetes than moderate-intensity statins 6.
• Genetic polymorphisms with reduced HMG CoA reductase function are associated with weight gain, insulin resistance, and diabetes 6.

Effects of Statins on Fasting Glucose

• A nationwide population-based health examination in Korea found that high adherence and intensive use of statins were significantly associated with an increase in fasting glucose of non-diabetic individuals 7.
• The use of atorvastatin, rosuvastatin, pitavastatin, and simvastatin were significantly associated with an increase in fasting glucose, while pravastatin, lovastatin, and fluvastatin had a non-significant trend toward an increased fasting glucose 7.

Physiological Mechanism for Increased Type 2 Diabetes Risk

• A clinical trial found that atorvastatin 40mg daily increased insulin resistance and insulin secretion in adults without known atherosclerotic cardiovascular disease or type 2 diabetes at baseline 8.
• The study suggested that the risk of new-onset diabetes with statin use may increase in individuals who become more insulin resistant but are unable to maintain compensatory increases in insulin secretion 8.