Diabetes Treatment (cont.)
Robert Ferry Jr., MD
Robert Ferry Jr., MD
Robert Ferry Jr., MD, is a U.S. board-certified Pediatric Endocrinologist. After taking his baccalaureate degree from Yale College, receiving his doctoral degree and residency training in pediatrics at University of Texas Health Science Center at San Antonio (UTHSCSA), he completed fellowship training in pediatric endocrinology at The Children's Hospital of Philadelphia.
Melissa Conrad Stöppler, MD
Melissa Conrad Stöppler, MD
Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.
In this Article
Thiazolidinediones: pioglitazone (Actos) and rosiglitazone (Avandia)
Thiazolidinedione drugs lower blood glucose by increasing the sensitivity of the cells to insulin (improving target cell response to insulin). Troglitazone (Rezulin) was the first of this class in the US; however it was taken off the market by the FDA IN 2000 because of severely toxic liver effects. Sister compounds with better safety profiles, pioglitazone (Actos) and rosiglitazone (Avandia), remain approved for use in the U.S.
Although similar to troglitazone, extensive studies have failed to associate pioglitazone and rosiglitazone with any liver problems. Both pioglitazone and rosiglitazone act by increasing the sensitivity (responsiveness) of cells to insulin. They improve the sensitivity of muscle and fat cells to insulin. These drugs effectively lower blood sugars in patients with type 2 diabetes.
Side effects, warnings, contraindications, and precautions of pioglitazone (Actos) and rosiglitazone (Avandia)
Rosiglitazone (Avandia) has been associated with an increased risk of heart attack and stroke, and experts have debated the severity of these concerns. On September 23, 2010, the U.S. FDA announced significant restrictions on rosiglitazone (Avandia) for those with type 2 diabetes. These new restrictions responded to data suggesting elevated risk of cardiovascular events (for example, heart attack and stroke) in patients treated with rosiglitazone. GlaxoSmithKline (the manufacturer of rosiglitazone) was required to establish a Risk Evaluation and Mitigation Strategy (REMS) program, with mandatory participation by patients, their health-care providers and pharmacists in order to receive, prescribe, or sell rosiglitazone.
While liver problems reported with these agents have been mild (and reversible with discontinuation of the drug), most health-care professionals follow the earlier recommendation monitor blood tests for potential liver injury (every two months or so) during the first year of therapy. This recommendation has recently been removed. If at any point the liver tests increase to three times the normal upper limit, the drug should be stopped.
The most important contraindications to thiazolidinediones include any type of liver disease or heart failure. Fluid retention can be of particular concern in patients with signs or symptoms of heart failure and in those with ejection fractions of less than 40% (poor heart function). While reports of weight gain usually range three to eight pounds, up to 12-15 pounds of weight gain can occur. Usually the majority of this gain is fluid, but absolute body weight gain can occur. Weight gain is usually dose-dependent, with greater weight gain at higher drug doses. Weight gain is more pronounced for patients taking insulin.
Generally, ankle swelling (edema) and puffiness due to the accumulation of fluid can be controlled by either reducing the drug dose or addition of a diuretic such as spironolactone (Aldactone); note that furosemide (Lasix) does not work as well. On occasion, patients may be symptomatic enough from fluid retention to warrant drug withdrawal. Some recent studies have suggested an association between untoward cardiac events and pioglitazone and rosiglitazone (for example, heart attacks), but this association is controversial. The controversy notwithstanding, it has been well established that pioglitazone and rosiglitazone should be avoided in patients with symptomatic heart failure or heart failure.
Another newer concern is an association of treatment with a small increase in the frequency of fractures of the distal long bones of the arms and legs. At present, this observation does not translate into fractures of the hip and spine, which would be more worrisome. More data is still needed to make a definitive statement about cause and effect.
As an aside, pioglitazone and rosiglitazone provide the added benefit of improving cholesterol patterns in people with diabetes. HDL (or desirable cholesterol) increases with these medications, and triglycerides often decrease. Despite some controversy about effect on undesirable cholesterol (LDL) levels, pioglitazone may be superior for changing lipid profiles than rosiglitazone. In type 2 diabetes patients who are already at increased risk for heart disease, improving the cholesterol profile benefits.
As more data become available, evidence is mounting that thiazolidinediones may provide direct benefits to the heart and large blood vessels. They may prevent progression to diabetes in prediabetic individuals at high risk by reducing inflammation and by decreasing clotting factors.
Medically Reviewed by a Doctor on 5/7/2015
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