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Avandia and Metformin have Synergistic Effects for Improved Gly

Adding Avandia® Increased Insulin Sensitivity, Improved Certain Lipid Parameters Without Hypoglycemia Results from a study published recently in Diabetes/Metabolism: Research and Reviews showed that adding the insulin sensitizing agent Avandia® (rosiglitazone maleate) to metformin significantly helped improve blood sugar levels in Mexican patients whose type 2 diabetes was inadequately controlled by metformin alone. Type 2 diabetes is the third leading cause of death in Mexico and is also a serious and growing problem among Mexican immigrants to the United States. Indeed, in the United States, diabetes currently affects more than one million Mexican- Americans, resulting in an increased incidence of diabetes-related complications compared to non-Hispanic Caucasians. This is largely attributed to a higher incidence of insulin resistance, an underlying cause of the disease.

In this controlled trial, researchers found that adding Avandia to metformin therapy had a positive effect on several metabolic deficiencies of type 2 diabetes, including insulin resistance and certain lipid parameters. Specifically, Avandia increased high density lipoprotein (HDL or "good") cholesterol, reduced triglycerides and significantly decreased free fatty acid levels. Elevated levels of free fatty acids have been associated with insulin resistance, and with possible damage to the insulin-producing beta cells in the pancreas. In addition, this study reported a low incidence of hypoglycemia (or low blood sugar) in all treatment groups.

"With complementary mechanisms of action, Avandia and metformin seem to be working in an additive fashion to achieve improved blood sugar levels, with a low risk of hypoglycemia." said Martin Freed, M.D., Global Vice President, Metabolism Therapeutic Area, Clinical Development and Medical Affairs, GlaxoSmithKline.

Avandia directly targets insulin resistance by increasing insulin sensitivity in the muscle and adipose tissue, while metformin primarily works by decreasing the output of glucose (or sugar) by the liver. Due to the limitations of traditional monotherapy, most patients require combination treatment in the long term. In fact, the United Kingdom Prospective Diabetes Study (UKPDS) showed that the majority of patients on metformin alone required combination therapy after three years.

Importance of Aggressive Diabetes Management
In the long term, untreated or poorly managed type 2 diabetes can lead to serious and life-threatening complications, including heart disease, heart attack, stroke, kidney disease, nerve damage and blindness. Importantly, this study in Mexican patients showed that A1C levels — the most effective measure of long-term diabetes control — were reduced significantly in more patients who received Avandia therapy added to metformin than in patients taking the highest dose of metformin alone. In contrast, A1C levels actually increased in the metformin treatment group.

Increases in A1C levels are directly linked to increases in a patient’s risk for cardiovascular disease, a serious diabetes-related complication. To help minimize complications, American Diabetes Association guidelines advocate A1C levels of less than seven percent as the target for diabetes control.

"It is clear from the results of our study, that adding Avandia to metformin significantly lowers A1C levels, improving blood sugar levels while minimizing the risk of hypoglycemia," said Francisco Gomez-Perez, M.D., Head, Endocrinology and Metabolism Department, Instituto Nacional de Ciencias Medicas y Nutricion "

Investigators found that compared with baseline levels and with metformin therapy alone, combination treatment significantly reduced levels of fasting plasma glucose and A1C in a dose-dependent manner. In addition, results of the study showed a decrease in insulin resistance as measured by the reduction of immunoreactive insulin and C-peptide levels in the Avandia groups.

Avandia-treated patients experienced increases in HDL cholesterol, reductions in triglyceride levels, and statistically significant reductions in concentrations of free fatty acids. Elevated levels of free fatty acids have been linked to insulin resistance; toxic effects on pancreatic beta cells; and possibly vascular abnormalities.

Overall, the Avandia regimens were well tolerated. The incidence of adverse events was similar in all three treatment groups, and patients in the Avandia treatment groups generally experienced minimal weight gain (<3 kg). There were no reports of significant hypoglycemia across treatment groups.
SOURCE: GlaxoSmithKline