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Diabetes drug improves metabolic changes
associated with HIV combination therapy
Positive results seen in patients
with insulin resistance, more reseach needed
BOSTON - May 17, 2004 - 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
Physician Referral Service: 1-800-388-4644
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