Why should patients with diabetes mellitus be on a HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor, commonly referred to as a statin?

From the Guidelines

Diabetics should be on a statin medication because they have a significantly higher risk of cardiovascular disease compared to non-diabetics, and statins have been shown to reduce this risk by lowering cholesterol levels, particularly LDL ("bad") cholesterol, as recommended by the American Diabetes Association standards of medical care in diabetes 2018 1. The use of statins in diabetic patients is supported by several studies, including a review of the American Diabetes Association standards of medical care in diabetes 2018, which recommends statin therapy for most persons with diabetes aged 40 years or older 1.

• The intensity of statin therapy depends on individual risk factors, with higher doses recommended for those with additional risk factors like hypertension, smoking, or family history of heart disease.
• Statins work by inhibiting an enzyme called HMG-CoA reductase, which plays a key role in cholesterol production in the liver.
• Beyond cholesterol reduction, statins also provide anti-inflammatory effects and help stabilize arterial plaques, further protecting against heart attacks and strokes.
• Side effects can include muscle pain, liver enzyme elevations, and slightly increased risk of diabetes, but the cardiovascular benefits typically outweigh these risks for diabetic patients, as shown in a study published in the Annals of Internal Medicine in 2018 1. Some key points to consider when prescribing statins to diabetic patients include:
• For primary prevention in patients aged 40 to 75 years without clinical ASCVD, moderate-dose statin therapy is recommended, although high-intensity therapy may be considered for certain patients with additional ASCVD risk factors 1.
• For secondary prevention in patients with ASCVD, high-intensity statin therapy is recommended, and recent randomized trials have shown reduced risk for ASCVD events with the addition of nonstatin agents such as ezetimibe or PCSK9 inhibitors to statin therapy 1.
• The American College of Cardiology/American Heart Association ASCVD risk calculator has limited use for assessing cardiovascular risk in persons with diabetes, and clinical judgment is necessary for patients with diabetes who are younger than 50 years and have several other risk factors 1.

From the Research

Benefits of Statins for Diabetics

• Statins are the mainstay of therapy for cardiovascular risk reduction in patients with diabetes mellitus, reducing the risk of mortality and morbidity by lowering blood low-density cholesterol 2.
• Multiple clinical trials have found evidence for statin use in patients with diabetes, for both primary prevention and secondary prevention, with the benefit of statins in patients with coronary heart disease and diabetes being twice as much as compared to the risk in patients with coronary heart disease but no diabetes 2.
• The proportion of patients with diabetes treated with statins has increased steadily over the past few decades, with a concurrent decrease in cardiovascular deaths in this high-risk population 2.

Risk of Diabetes with Statin Use

• Statins have been associated with an increased risk of new-onset diabetes, particularly with high-intensity statin treatment, and in patients at risk for the development of diabetes 3, 4.
• The mechanisms explaining statin diabetogenicity include impaired insulin secretion by pancreatic β cells together with increased insulin resistance of various tissues, with lipophilic statins being more diabetogenic than hydrophilic ones 3.
• However, the cardiovascular outcome benefits from statin use outweigh the diabetes risk, and patients at risk for the development of diabetes should be prescribed statins with caution 3, 4.

Alternative Treatment Options

• The combination of rosuvastatin and ezetimibe has been shown to be safe and effective in patients with hypercholesterolemia or dyslipidemia, with or without diabetes, and with or without cardiovascular disease, enabling higher proportions of patients to achieve recommended LDL-C goals 5.
• Switching to an ezetimibe/simvastatin combination has been found to provide significantly greater reductions in LDL-C and achievement of LDL-C targets compared to statin doubling or switching to rosuvastatin in diabetic patients with symptomatic cardiovascular disease 6.