#23–Tom Dayspring Part IV of V: statins, Zetia, PCSK9 inhibitors, niacin, cholesterol & the brain
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Mechanism
Fibrates, including phenofibrate and gemfibrozil, are lipid-modifying agents primarily used to manage triglyceride levels. explains that gemfibrozil, a prodrug, requires conversion to its active form, while phenofibrate is immediately active, offering better bioavailability 1. Despite their potential, fibrates are underutilized, often overshadowed by statins due to historical trial designs and statin prevalence. Dayspring notes, "Fibrates reduce amputations, neuropathic ulcers, improve renal disease. Save your eyes. Why the hell are you not on a fibrate if you're a diabetic?" 2.
Trial Insights
Clinical trials have shown fibrates' unique benefits, particularly in diabetic patients with elevated triglycerides and low HDL cholesterol. highlights that fibrates can reduce microvascular complications like retinopathy and neuropathy, outcomes not typically achieved by other lipid drugs 2. Despite these promising results, the trials were often compromised by concurrent statin use, which muddled the data. Dayspring remarks, "That's where the outcome reduction was very interesting, which no other lipid drug has ever done" 3.
Interactions
Fibrates are generally well-tolerated, but they do have notable drug interactions. warns that phenofibrate can interact with anticoagulants like warfarin, enhancing their effects, while gemfibrozil can significantly increase statin levels, raising the risk of muscle-related side effects 4. Despite these interactions, phenofibrate is often preferred due to its compatibility with statins. Dayspring advises, "If you want to use a fibrate, I strongly encourage you...to use phenofibrate, because you're going to be using it with a statin in the vast majority of cases" 5.