Why should patients with diabetes mellitus take statin (HMG-CoA reductase inhibitor)?

From the Guidelines

Diabetics should take statins because these medications significantly reduce their elevated risk of cardiovascular disease, as evidenced by the most recent and highest quality study 1. People with diabetes have a 2-4 times higher risk of heart attacks and strokes compared to those without diabetes, even when blood sugar is well-controlled. Common statins prescribed for diabetics include atorvastatin (10-80mg daily), rosuvastatin (5-40mg daily), and simvastatin (10-40mg daily). Most guidelines recommend statin therapy for diabetics aged 40-75, regardless of cholesterol levels, and especially for those with additional risk factors like high blood pressure or smoking. Statins work by blocking an enzyme in the liver that produces cholesterol, thereby lowering LDL ("bad") cholesterol levels by 20-60%. Beyond cholesterol reduction, statins also have anti-inflammatory effects that help stabilize arterial plaques. Side effects can include muscle pain, liver enzyme elevations, and slightly increased blood sugar levels, but the cardiovascular benefits typically outweigh these risks, as shown in a study published in Diabetes Care 1. Regular follow-up with healthcare providers is important to monitor for side effects and ensure the medication is working effectively. Some key points to consider when prescribing statins for diabetics include:

• High-intensity statin therapy is recommended for all people with diabetes and ASCVD to target an LDL cholesterol reduction of ≥50% from baseline and an LDL cholesterol goal of <55 mg/dL 1.
• The decision to add a nonstatin agent should be made following a clinician-patient discussion about the net benefit, safety, and cost of combination therapy 1.
• Statins are the agents of choice for lipid-lowering therapy in patients with diabetes, with moderate doses being the minimum recommended 1.
• The primary prevention trials do not provide adequate evidence to guide drug choice because most of the diabetes subgroups were too small 1.
• No clinical trials inform the use of one statin over another, and more aggressive titration of statins or use of combination lipid-lowering treatment titrated on the basis of LDL cholesterol levels should be a shared decision between the physician and the patient 1.

From the FDA Drug Label

To reduce the risk of: ... MI and stroke in adults with type 2 diabetes mellitus with multiple risk factors for CHD but without clinically evident CHD. Patients with diabetes mellitus should take statin (HMG-CoA reductase inhibitor) to reduce the risk of myocardial infarction (MI) and stroke.

• The primary reason is that statins have been shown to reduce the risk of MI and stroke in adults with type 2 diabetes mellitus who have multiple risk factors for coronary heart disease (CHD) but do not have clinically evident CHD 2.

From the Research

Benefits of Statin Therapy in Diabetes Mellitus

• 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 3.
• The benefit of statins in patients with coronary heart disease and diabetes is significant, with an absolute risk reduction twice as much as compared to the risk in patients with coronary heart disease but no diabetes 3.
• Statins have been shown to reduce cardiovascular mortality, with multiple clinical trials finding evidence for statin use in patients with diabetes for both primary and secondary prevention 3, 4.

Mechanisms and Risks Associated with Statin Therapy

• While statins have been associated with an increased risk of new-onset diabetes mellitus, the incidence of this adverse effect is not negligible, especially for specific subsets of patients 5, 6, 7.
• The mechanisms proposed for statin-associated diabetes risk include increased insulin resistance, impaired insulin secretion, and genetic polymorphisms with reduced HMG CoA reductase function 7.
• However, the excess risk of diabetes appears to be confined to those who are already at risk for developing diabetes, and the clinical impact of statin-associated diabetes is likely unimportant compared to the cardiovascular risk reduction benefit 7.

Clinical Recommendations and Guidelines

• Statins remain the cornerstone for primary and secondary cardiovascular prevention, but specific attention to glucose metabolism and metabolic syndrome features should be given before and during statin treatment, especially in cohorts at greater risk 6.
• A potential tailored statin treatment based on the patient's cardiovascular and metabolic risk profile might emerge as the safest therapeutic approach 6.
• Newer agents for add-on therapies to statins are now available for additional cardiovascular risk reduction, and individualized treatment selection is necessary to mitigate cardiovascular risk 4.