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Using the Glitazones to Manage Diabetes
Am Fam Physician. 2001 Jan 15;63(2):369.
Type 2 diabetes mellitus (formerly known as non–insulin-dependent diabetes) features early onset of insulin resistance. This leads to hyperinsulinemia with resultant elevation of blood glucose when the pancreas can no longer keep up with increased insulin requirements. Often, patients with hyperinsulinemia and diabetes also have hypertension, obesity and dyslipidemia, all occurring in a disorder constellation often referred to as “syndrome X” or “metabolic syndrome.” The glitazones act on liver and skeletal muscle, sensitizing them to insulin action, resulting in increased glucose uptake and decreased hepatic output. Krische reviewed the current uses for glitazones.
The oldest and best-studied preparation is troglitazone. Although this agent decreased concentrations of fasting blood glucose and glycosylated hemoglobin (HbA1c), it was removed from the market by the U.S. Food and Drug Administration on March 21, 2000, because of safety concerns. Rosiglitazone also decreases fasting plasma glucose levels and HbA1c levels. Efficacy is enhanced with twice-daily dosing. When used with insulin, daily insulin requirements decreased by 4.8 to 9.4 percent. However, more symptoms of hypoglycemia occurred in patients using the combination rather than insulin alone. Side effects are mild to moderate, with the most frequent adverse effect being edema. Pioglitazone is the third agent in the glitazone family and works similarly to rosiglitazone.
The two glitazones still on the market, pioglitazone and rosiglitazone, have similar efficacy and are more effective than placebo in reducing fasting plasma glucose and HbA1c concentrations. These effects are dose related. Because serious side effects have occurred with these agents, notably edema, hepatotoxicity and weight gain, use should be discontinued if no clinical improvement occurs within eight to 12 weeks.
Although the link between hepatotoxicity and troglitazone is clear, the connection with the two other agents is less certain. A few cases of hepatotoxicity have been reported with rosiglitazone use. Following the guidelines for monitoring liver aminotransferase levels in patients taking glitazones is essential to safe prescribing. Because edema and weight gain have been reported with all of the glitazone agents, use of these medications in patients with New York Heart Association class III or IV status should be avoided unless the benefits outweigh the risks. Weight gain is thought to occur because of fluid retention and, possibly, enhanced fat accumulation. Body weights should be measured in all patients receiving any glitazone.
The author concludes that the glitazones may be useful in carefully selected patients to achieve better glycemic control by selectively decreasing insulin resistance. Fasting plasma glucose and HbA1c levels may be reduced in some patients. Monitoring for adverse effects must include repeated body weight measurements and periodic liver function tests. Monotherapy may be useful in a few patients, but the high cost of therapy and the reports of hepatotoxicity, edema and weight gain suggest that other agents should be used first for monotherapy of hyperglycemia in patients with diabetes. Glitazones are best saved for combination therapy with other oral diabetic drugs to control glucose metabolism.
Krische D. The glitazones: proceed with caution. West J Med. July 2000;173:54–57.
Copyright © 2001 by the American Academy of Family Physicians.
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