Is statin therapy still indicated in a patient with type 2 diabetes (T2D) and a low-density lipoprotein (LDL) level already at target?

From the Guidelines

Statin therapy is still indicated in patients with type 2 diabetes (T2D) even if their LDL cholesterol is already at target levels, as the benefits of statin therapy extend beyond LDL lowering and are based on the patient's overall cardiovascular risk. The recommendation for statin use in T2D is based on the patient's overall cardiovascular risk rather than just their LDL level, as diabetes itself is considered a major risk factor for cardiovascular disease, conferring a 2-4 fold increased risk of cardiovascular events compared to those without diabetes 1. Statins provide benefits beyond LDL lowering, including anti-inflammatory effects, plaque stabilization, and improved endothelial function, and have demonstrated significant reduction in cardiovascular events and mortality in diabetic patients across various LDL levels 1. For optimal protection, moderate to high-intensity statin therapy is typically recommended for most T2D patients, with the specific agent and dose tailored to the individual's age, comorbidities, and potential drug interactions. Some key points to consider when prescribing statin therapy in T2D patients include:

• The cardiovascular benefit of statin therapy does not depend on baseline LDL cholesterol levels and is linearly related to the LDL cholesterol reduction without a low threshold beyond which there is no benefit observed 1
• Statins are the drugs of choice for LDL cholesterol lowering and cardioprotection in patients with T2D 1
• Regular monitoring of liver function and muscle symptoms remains important during ongoing statin therapy. Key considerations for statin dosing include:
• High-intensity statin therapy will achieve an approximately ≥50% reduction in LDL cholesterol, and moderate-intensity statin plans achieve 30–49% reductions in LDL cholesterol 1
• The maximum tolerated statin dose should be used for individuals who do not tolerate the intended intensity of statin 1. Overall, the use of statin therapy in patients with T2D, even those with LDL cholesterol at target levels, is supported by strong evidence and should be considered a standard part of cardiovascular risk management in these patients 1.

From the Research

Statin Therapy in Type 2 Diabetes with Low LDL Levels

• The use of statin therapy in patients with type 2 diabetes (T2D) and low-density lipoprotein (LDL) levels already at target is a topic of interest, given the potential benefits and risks associated with statin treatment 2, 3, 4, 5, 6.
• According to the American College of Cardiology and the American Heart Association guidelines, moderate-intensity or high-intensity statin therapy is recommended for primary prevention in individuals with diabetes mellitus, aged between 40 and 75 years, and with LDL-C from 70 to 189 mg/dL 2.
• A study published in 2020 found that switching from low-dose statin to high-intensity statin in T2D patients with achieved plasma LDL-C <100 mg/dl resulted in a significant reduction in plasma LDL-C levels, and was fairly well tolerated during a 12-week study period 3.
• Another study published in 2013 highlighted the importance of achieving LDL cholesterol targets in diabetic patients, and suggested that rosuvastatin, a potent statin, can effectively reduce LDL cholesterol to recommended targets in diabetics 4.
• A target trial emulation study published in 2024 found that initiating statin therapy in patients with T2D and baseline LDL-C levels of 1.8-2.5 mmol/L (i.e., 70-99 mg/dL) can further reduce the risks of cardiovascular disease and all-cause mortality without significantly increasing the risk of major adverse events 5.
• A population-based cohort study published in 2022 found that statin therapy duration is as important as or more crucial than statin intensity or achieved LDL-C level for the reduction of cardiovascular risk in T2D patients, suggesting that "longer is better" regarding statin therapy 6.

Risks and Benefits of Statin Therapy

• The benefits of statin therapy in patients with T2D and low LDL levels include a reduced risk of cardiovascular events and all-cause mortality 2, 3, 5, 6.
• However, statin therapy is also associated with potential risks, such as an increase in glycated hemoglobin A1C (HbA1C) and fasting plasma glucose (FPG) levels, as well as a higher risk of discontinuation due to adverse effects 2, 3.
• The choice of statin and its intensity can also impact the risk-benefit profile, with some statins, such as pitavastatin, showing a more favorable effect on glycemic control compared to others, such as atorvastatin 2.

Considerations for Statin Therapy in T2D Patients with Low LDL Levels

• When considering statin therapy in T2D patients with low LDL levels, healthcare providers should weigh the potential benefits and risks, taking into account the individual patient's characteristics, such as age, cardiovascular risk factors, and glycemic control 2, 3, 4, 5, 6.
• The use of moderate-intensity or high-intensity statin therapy may be considered in patients with T2D and low LDL levels, particularly if they have other cardiovascular risk factors or a high risk of cardiovascular events 2, 3, 5, 6.
• Regular monitoring of LDL levels, glycemic control, and potential adverse effects is essential to ensure the safe and effective use of statin therapy in T2D patients with low LDL levels 2, 3, 4, 5, 6.