Table 7.
Therapeutic agents affecting triglyceride levels.
| Class | Agent | Mechanism of Action | Dose | TG Reduction | Comments |
|---|---|---|---|---|---|
| Fibrates | Fenofibrate | Increases TRL catabolism via activation of PPARα and LPL and inhibition of ApoC3 and hepatic synthesis of VLDL | 160–267 mg OD | Up to 50% | No effect on gut-derived chylomicrons. Reduces VLDL particles. Minimal or no effect in FCS patients. |
| Gemfibrozil * | 600 mg BD | ||||
| Bezafibrate | 200 mg TDS | ||||
| Pemafibrate ** | 0.4 mg OD | ||||
| Vitamin B3 | Niacin | Inhibits HSL, reduces FFA delivery to the liver, inhibits DAGAT II, reduces VLDL production | 2 g daily | 15–30% | Less effective when TG is very high. Improves HDL function and reduces Lp(a). May worsen diabetes. Not available in Europe for clinical use. |
| Omega-3 Fatty acids | O3AEE, EPA+DHA (Omacor/Lovaza) | Inhibits VLDL production, Inhibits ApoC 3, increases chylomicron clearance by activating LPL | 4 g daily | 20–30% | Less effective in chylomicronaemia of monogenic origin. Epanova is not commercially available. Vazkepa is the only purified EPA derivative without DHA. |
| O3CA, EPA+DHA (Epanova) | |||||
| IPE (Vazkepa) | |||||
| Gut lipase inhibitor | Orlistat | Gastric and pancreatic lipase inhibitors. Reduces the absorption of fat and chylomicron production | 120 mg TDS | 30–50% | Phase II clinical trial for FCS is ongoing. |
| Leptin Analogue | Metreleptin | Leptin receptor activator | Weight- and Gender-dependent | 30–35% | Approved by NICE for lipodystrophies. |
* Increased risk of rhabdomyolysis when given with statins. ** on 8 April 2022, Kowa Research Institute, Inc., declares the decision not to continue the phase III PROMINENT study, after recommendations of the Data Safety Monitoring Board (DSMB). Based on the review of a planned interim analysis, the DSMB determined that the primary endpoint was unlikely to be met. No safety concerns were raised. DGAT II: diacylglycerol acyltransferase-2; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; FCS: familial chylomicronaemia syndrome; HSL: hormone-sensitive lipase; IPE: icosapent-ethyl; LPL: lipoprotein lipase; NICE: National Institute of Health and Care Excellence; O3AEE: omega-3 acid ethyl esters; O3CA: omega-3 carboxylic acid; PPAR: peroxisome proliferator-activated receptors; TRL: triglyceride-rich lipoproteins; VLDL: very-low-density lipoprotein.