Do 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, commonly referred to as statins, increase the risk of developing diabetes mellitus?

From the Guidelines

Yes, statins can increase the risk of developing type 2 diabetes, though the risk is relatively small compared to their cardiovascular benefits. The most recent and highest quality study, published in 2023 1, reports a modestly increased risk of incident diabetes with statin use, which may be limited to those with diabetes risk factors. This study found that the absolute risk increase was small, with 1.2% of participants on placebo developing diabetes and 1.5% on rosuvastatin developing diabetes over 5 years of follow-up.

Key Points

• The risk of developing type 2 diabetes with statin use is more pronounced in people who already have risk factors for diabetes, such as obesity, elevated fasting blood glucose, or metabolic syndrome.
• Statins may contribute to diabetes development by decreasing insulin sensitivity and reducing insulin secretion from pancreatic beta cells.
• Despite this risk, for most patients with cardiovascular disease or at high risk for it, the benefits of statins in preventing heart attacks and strokes substantially outweigh the small increased diabetes risk.
• Patients taking statins should have their blood glucose monitored periodically, especially those with pre-existing risk factors for diabetes, as recommended by the 2024 standards of care in diabetes 1.

Recommendations

• Statin therapy may increase the risk of type 2 diabetes in people at high risk of developing type 2 diabetes, and glucose status should be monitored regularly in such individuals 1.
• Diabetes prevention approaches should be reinforced in individuals taking statins, especially those with prediabetes or other cardiovascular risk factors.
• The benefits of statins in preventing cardiovascular events should be weighed against the potential risk of developing type 2 diabetes, and treatment decisions should be made on a case-by-case basis.

From the FDA Drug Label

1. 4 Increases in HbA1c and Fasting Serum Glucose Levels Increases in HbA1c and fasting serum glucose levels have been reported with statins, including atorvastatin.

Statins, including atorvastatin, may increase the risk of developing diabetes due to reported increases in HbA1c and fasting serum glucose levels.

• It is recommended to optimize lifestyle measures to minimize this risk, including regular exercise, maintaining a healthy body weight, and making healthy food choices 2.

From the Research

Statin Use and Risk of Type 2 Diabetes

• Statins are associated with an increased risk of type 2 diabetes, particularly with the use of high-intensity statins that reduce low-density lipoprotein cholesterol (LDL-C) by 50% or more 3, 4.
• The increase in type 2 diabetes risk with statin therapy appears to be attributable mainly to those with major type 2 diabetes risk factors, with an approximate 25% increase in incidence compared to placebo or moderate-intensity statin therapy 3.
• However, the number of cardiovascular disease events prevented for each excess case of type 2 diabetes is close to or greater than one, indicating that the risk-benefit ratio still strongly favors the use of statin therapy or intensive statin therapy for patients with sufficient cardiovascular disease risk 3.

Mechanisms and Clinical Implications

• Statins have been shown to increase insulin resistance and insulin secretion, which may contribute to the increased risk of type 2 diabetes 5.
• The mechanisms by which statins increase the risk of type 2 diabetes are not fully understood, but may involve changes in glucose and insulin metabolism 4, 5.
• Clinical implications of statin use and type 2 diabetes risk include the need for careful evaluation of the type 2 diabetes risk factor profile before initiation of and during statin therapy, as well as emphasis on lifestyle management and other preventive measures to manage risks for both type 2 diabetes and cardiovascular disease events 3, 6.

Efficacy and Safety of Statin Therapy

• Switching from low-dose statins to high-intensity statins has been shown to result in a significant reduction in plasma LDL-C levels, but may be associated with an increased risk of adverse effects, such as discontinuation of statin due to adverse effects 7.
• The efficacy and safety of statin therapy for primary prevention in type 2 diabetes patients who have achieved plasma LDL-C targets with low-dose statin treatment are still being studied, with some evidence suggesting that high-intensity statin therapy may be beneficial in reducing cardiovascular disease risk, but may also increase the risk of type 2 diabetes 7.