The peroxisome proliferator-activated receptor (PPAR) agonists are medications that can be used to treat type 2 diabetes mellitus (DM) and hypercholesterolemia, a condition in which patients have high cholesterol levels in their blood. A PPAR agonist acts by stimulating the PPA receptors, causing changes in the body’s metabolism and growth. The thiazolidinediones bind to the gamma subtype of the PPA receptors and are used to treat type 2 DM, whereas the fibrates bind to the alpha subtype and help treat hypercholesterolemia.
A PPAR agonist works because it stimulates the peroxisome proliferator-activated (PPA) receptors, which are located inside the nuclei of many cells throughout the body. There are a number of different subtypes of these receptors, including the alpha receptor, beta receptor, and gamma receptor. These subtypes cause different cellular responses. In general, however, stimulation of the receptors activates different genes, and results in the regulation of the body’s metabolism and growth.
One type of PPAR agonist is the thiazolidinedione class, which binds to the gamma receptor subtype. By activating this subtype, these medications can increase the body’s sensitivity to insulin and decrease the appetite. Since DM type 2 develops due to insulin resistance, the thiazolidinediones can effectively treat this disease. The most commonly used members of this class of drugs are rosiglitazone, which goes by the trade name Avandia®, and pioglitazone, which has the brand name Actos®.
The thiazolidinediones can either be used alone or in combination with other medications to treat type 2 DM. They successfully lower patients’ average blood glucose levels. Common side effects of these drugs include weight gain and low blood glucose. Some doctors have questioned whether the thiazolidinediones are safe because they have been shown to worsen heart failure and cause liver damage in some patients. These drugs, however, are still commonly used to treat type 2 DM.
Unlike the thiazolidinediones, fibrates are a type of PPAR agonist that bind to the alpha receptor subtype. This medication class is used to treat hypercholesterolemia. Stimulation of the alpha receptors increases high density lipoprotein (HDL) levels and decreases low density lipoprotein (LDL) levels. This is beneficial because high LDL levels are associated with an increased risk of heart attack and stroke, whereas high HDL levels are protective against these diseases. The most commonly used fibrates include fenofibrate, gemfibrozil, ciprofibrate, and bezafibrate.
The fibrates are often used in conjunction with other medications to treat hypercholesterolemia. Common side effects of the fibrates include muscle pain and stomach pain. Rarely, these medications can cause a condition called rhabdomyolysis, which is a drug reaction that results in a massive breakdown of muscle tissue.