Diabetes drug improves metabolic changes associated with HIV combination therapy

Use of an oral antidiabetes medication produced significant improvement in a group of patients with HIV lipodsytrophy, a syndrome involving the redistribution of fat and other metabolic changes in those receiving combination drug therapy for HIV infection. In the May 18 Annals of Internal Medicine, researchers from Massachusetts General Hospital (MGH) report that daily doses of rosiglitazone (Avandia) improved insulin sensitivity and alleviated fat redistribution in patients with lipodystrophy and insulin resistance.

The drug combination strategy known as highly active antiretrovial therapy (HAART) can significantly reduce viral levels and help maintain health in HIV-infected individuals, but a significant number can develop lipodystrophy. Typical symptoms of the syndrome may include a loss of subcutaneous fat in the face, arms, and legs; increased fat deposits in the abdomen and upper back; changes in cholesterol and other blood lipids; and insulin resistance.

"The metabolic complications of this condition are becoming more significant as patients spend more time on HAART," says Colleen Hadigan, MD, MPH, of the MGH Neuroendocrine Unit and Program in Nutritional Metabolism, the report's lead author. "For example, we now know that 14 percent of men on this therapy may develop type 2 diabetes, which is four times the usual risk; and concerns are also increasing about the related risk of heart disease."

Although previous studies have examined the effect of rosiglitazone and similar medications on HIV lipodystrophy, the results have been inconclusive. Since patients with the syndrome may have a variety of associated symptoms, the current study was limited to participants who had developed insulin resistance. The 27 enrolled patients were randomized to receive daily doses of either rosiglitazone or a placebo, and neither participants nor the researchers knew who was receiving the active medication.

At the end of the three-month study period, participants who received rosiglitazone were found to have a 20 percent improvement in insulin sensitivity, based on a standard test called an insulin clamp. Both physical measurements and CT scans showed that those on the active medication had significant increases in total body fat, particularly in their extremities. Peripheral fat measurements increased by 24 percent in the treatment group but decreased by 2 percent in the placebo group.

"We were able to demonstrate that this class of agents can slow down or reverse fat loss in patients with fat atrophy," says Hadigan. "However there are still a lot of questions to be answered about safety before these results can be widely applied. For example, those taking rosiglitazone had increases in both total and LDL cholesterol, but there were changes in other metabolic markers which might protect against cardiovascular disease. Larger and longer trials of this drug and related medications are needed to determine the best therapeutic approaches for individual patients." Hadigan is an assistant professor of pediatrics at Harvard Medical School.

Other authors of the Annals report are senior author Steven Grinspoon, MD, and Fiona Havers of the MGH Neuroendocrine Unit and Program in Nutritional Metabolism; and Sigal Yawetz, MD, Abraham Thomas, MD, and Paul Sax, MD, of Brigham and Women's Hospital. The study was supported by grants from the National Institutes of Health.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $400 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.

Media Contact: Sue McGreevey, MGH Public Affairs

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