Fibrates are the most important drugs for lowering triglycerides. They are especially high-yield for exams because of their PPAR-α mechanism, their role in preventing pancreatitis, and classic questions about myopathy when combined with statins.
What Are Fibrates?
Fibrates are lipid-lowering drugs primarily used to treat hypertriglyceridemia.
Key Lipid Effect (One-Line)
Fibrates ↓ triglycerides the most and ↑ HDL
Why Triglycerides Matter
Very high triglycerides (>500 mg/dL):
- Increase risk of acute pancreatitis
- Are poorly controlled by statins alone
Fibrates are the drugs of choice in severe hypertriglyceridemia.
Mechanism of Action (Very High-Yield)
Fibrates activate PPAR-α (Peroxisome Proliferator-Activated Receptor-alpha) in the liver.
Step-by-Step Mechanism
1. Activation of PPAR-αOne-Line Exam Answer
Fibrates lower triglycerides by activating PPAR-α and increasing lipoprotein lipase
Effects of Fibrates on Lipid Profile
| Lipid | Effect |
|---|---|
| Triglycerides | ↓↓↓ (major effect) |
| HDL | ↑ |
| LDL | ↓ (mild, variable) |
| VLDL | ↓↓↓ |
Main Drugs in This Class
1. Gemfibrozil
Prototype fibrate
Key Features
- Shorter acting
- Strong triglyceride reduction
Clinical Uses
- Severe hypertriglyceridemia
- Type III hyperlipoproteinemia
- Prevention of pancreatitis
Important Exam Point
High risk of myopathy when combined with statins
2. Fenofibrate
Preferred modern fibrate
Key Features
- Longer acting
- Better tolerated with statins
Clinical Uses
- Hypertriglyceridemia
- Mixed dyslipidemia
- Diabetic dyslipidemia
Exam Pearl
✔ Fenofibrate is safer than gemfibrozil with statins
Gemfibrozil vs Fenofibrate (High-Yield Table)
| Feature | Gemfibrozil | Fenofibrate |
|---|---|---|
| Duration | Short | Long |
| Statin combination | Risky | Safer |
| Triglyceride lowering | Strong | Strong |
| Current preference | Less | More |
Clinical Uses of Fibrates (Grouped)
Primary Indication
Severe hypertriglyceridemia (>500 mg/dL)Secondary Uses
- Mixed dyslipidemia
- Low HDL with high TG
- Diabetic dyslipidemia
Goal: prevent pancreatitis, not primarily ASCVD risk reduction.
Fibrates vs Statins (Exam Favorite)
| Feature | Fibrates | Statins |
|---|---|---|
| Main lipid ↓ | Triglycerides | LDL |
| Best for | Pancreatitis risk | CV risk |
| HDL effect | ↑ | Mild ↑ |
| Myopathy risk | Moderate | Moderate |
Adverse Effects (Very Important)
Muscle
- Myopathy
- Rhabdomyolysis (↑ risk with statins)
GI
- Dyspepsia
- Abdominal pain
Gallbladder
Gallstones (↑ cholesterol excretion in bile)Liver
Mild ↑ liver enzymesContraindications (Exam Gold)
❌ Severe renal disease
❌ Severe liver disease
❌ Gallbladder disease
❌ Caution with statins (especially gemfibrozil)
Drug Interactions (High-Yield)
- Fibrates + statins → ↑ myopathy risk
- Gemfibrozil + statins = highest risk
- Fenofibrate is the preferred fibrate if combination therapy is needed
Special Exam-Oriented Pearls
- Fibrates are not first-line for LDL reduction
- Best drugs to prevent hypertriglyceridemia-induced pancreatitis
- Act via nuclear receptor (PPAR-α)
- Fenofibrate preferred in diabetes
Easy Memory Tricks
- “FIBRates Fix Fatty TGs”
- “PPAR-α = Powerfully Processes lipids”
- “GEM + statin = Gym pain (myopathy)”
FAQs
1. What is the main use of fibrates?
To lower high triglyceride levels.
2. Which lipid is most reduced by fibrates?
Triglycerides.
3. How do fibrates work?
By activating PPAR-α and increasing lipoprotein lipase.
4. Which fibrate is safer with statins?
Fenofibrate.
5. Why are fibrates used in pancreatitis prevention?
They rapidly lower very high triglycerides.
6. Do fibrates increase HDL?
Yes, they moderately increase HDL.
7. What is a major adverse effect of fibrates?
Myopathy, especially with statins.
8. Can fibrates cause gallstones?
Yes.
9. Are fibrates first-line for cholesterol control?
No, statins are first-line for LDL reduction.
10. Which fibrate is older?
Gemfibrozil.
