What is the most suitable initial medication for a patient with Diabetes Mellitus (DM), hypercholesterolemia, marginally reduced High-Density Lipoprotein (HDL), and markedly elevated hypertriglyceridemia?

From the Guidelines

For a patient with Diabetes Mellitus, hypercholesterolemia, marginally reduced HDL, and markedly elevated hypertriglyceridemia, the most suitable initial medication would be a fibrate, specifically fenofibrate, as it primarily targets elevated triglycerides while also modestly improving HDL levels and reducing LDL cholesterol, as recommended by the most recent guidelines 1. The typical starting dose is 145 mg once daily with food. Fenofibrate works by activating peroxisome proliferator-activated receptor alpha (PPAR-α), which increases lipoprotein lipase activity and reduces apolipoprotein C-III production, enhancing triglyceride clearance from the bloodstream. Some key points to consider when treating this patient include:

• Before starting treatment, baseline liver function tests and creatinine should be checked, with follow-up labs in 4-6 weeks to assess efficacy and monitor for side effects, as suggested by various studies 1.
• Patients should be advised that maximum triglyceride reduction may take 2-4 weeks to achieve.
• For diabetic patients specifically, controlling hypertriglyceridemia is important as it can reduce the risk of pancreatitis and may help improve overall cardiovascular risk, though the patient should continue appropriate diabetes management and statin therapy may still be needed to address LDL cholesterol goals, as noted in several guidelines and studies 1.
• The combination of statins with nicotinic acid and especially with gemfibrozil or fenofibrate may carry an increased risk of myositis, although the risk of clinical myositis appears to be low, as mentioned in some studies 1.
• Improved glycemic control can be very effective for reducing triglyceride levels and should be aggressively pursued, as recommended by several studies and guidelines 1.

From the FDA Drug Label

For the treatment of adult patients with primary hypercholesterolemia or mixed hyperlipidemia, the initial dose of fenofibrate tablets is 160 mg per day. For adult patients with hypertriglyceridemia, the initial dose is 54 to 160 mg per day The effects of fenofibrate at a dose equivalent to 160 mg fenofibrate tablet per day were assessed from four randomized, placebo-controlled, double-blind, parallel-group studies including patients with the following mean baseline lipid values: total-C 306. 9 mg/dL; LDL-C 213.8 mg/dL; HDL-C 52.3 mg/dL; and triglycerides 191. 0 mg/dL. Fenofibrate tablets therapy lowered LDL-C, Total-C, and the LDL-C/HDL-C ratio. Fenofibrate tablets therapy also lowered triglycerides and raised HDL-C In a subset of the subjects, measurements of apo B were conducted. Fenofibrate tablets treatment significantly reduced apo B from baseline to endpoint as compared with placebo (-25. 1% vs. 2.4%, p<0. 0001, n=213 and 143 respectively). The most suitable initial medication for a patient with Diabetes Mellitus (DM), hypercholesterolemia, marginally reduced High-Density Lipoprotein (HDL), and markedly elevated hypertriglyceridemia is Fenofibrate.

• Key benefits of fenofibrate include:
  • Lowering of LDL-C, Total-C, and the LDL-C/HDL-C ratio
  • Reduction of triglycerides and increase of HDL-C
  • Significant reduction of apo B 2 2

From the Research

Clinical Scenario

The patient has Diabetes Mellitus (DM), elevated cholesterol, marginally reduced High-Density Lipoprotein (HDL), and markedly elevated triglyceride levels.

Suitable Medication Options

• Statins: Statins are the first choice for treating increased cardiovascular disease (CVD) risk due to raised non-HDL-C 3. They are effective in reducing CVD events in all patients, including those with DM.
• Fibrates: Fibrates may continue to have a role in the treatment of extreme hypertriglyceridaemia and in mixed hyperlipidaemia as they reduce CVD events and have additional benefits in improving diabetes and microvascular outcomes 3. They are also recommended for add-on therapy to treat elevated triglyceride or low HDL-C levels in high-risk patients with T2D and dyslipidaemia 4.
• Omega-3 fatty acids: Omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin for reducing triglyceride levels in patients with hypertriglyceridemia 5. However, further large-scale clinical studies are required to evaluate their effects on cardiovascular outcomes and CVD risk reduction.
• Niacin: Niacin will have little role in the treatment of hyperlipidaemia 3.

Treatment Approach

The treatment approach should focus on achieving the patient's low-density lipoprotein cholesterol goal, followed by their non-high-density lipoprotein cholesterol goal 6. Statins should be considered as the first line of therapy, with fibrates or omega-3 fatty acids added as needed to reduce triglyceride levels and improve HDL-C levels.

Key Considerations

• The patient's DM and hypertriglyceridemia increase their risk of CVD, and treatment should aim to reduce this risk 5, 4.
• The choice of medication should be based on the patient's individual risk factors and lipid profile 3, 6.
• Regular monitoring of lipid levels and cardiovascular risk factors is essential to adjust treatment as needed 4.