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Can Glitazones Reverse Lipoatrophy?

November 2004

A recently published study found that an anti-diabetes drug, called rosiglitazone (Avandia), is able to reverse the loss of fat under the skin (lipoatrophy) that some people with HIV experience. While these results are encouraging, they are just the latest in a series of conflicting study results involving two different glitazone drugs.

What Are Glitazone Drugs?

Rosiglitazone and pioglitazone (Actos) are both approved to treat insulin resistance and are frequently a part of type 2 diabetes treatment. Both showed promise in small studies initiated in 2001 in people with HIV who had lipoatrophy. Unfortunately, both have side effects and may not be safe for people with active liver disease. They may also be difficult to use in people with heart disease and high cholesterol as they can interact with common cholesterol-lowering drugs, and can cause fluid retention.

Some researchers considered rosiglitazone dead in the water after a large controlled study reported in early 2004 found no improvements in body fat among those using the drug. Though this latest study was much smaller, its results are compelling enough to warrant further research. The only other treatments for lipoatrophy involve avoiding or replacing anti-HIV drugs that contribute to fat loss -- a strategy that's not proven wonderfully effective in managing lipoatrophy -- or investigating purely cosmetic approaches (such as facial implants).

In the study published earlier in 2004, 108 people with lipodystrophy received 4 mg of rosiglitazone twice daily or a placebo for 48 weeks. Despite improvements in insulin resistance and another marker connected to fat accumulation, the investigators found no statistically significant increase in limb fat in the group receiving rosiglitazone compared to the group receiving the placebo.

In the more recent study, 28 people with lipodystrophy received either 4 mg of rosiglitazone once daily or placebo for three months. This study found dramatic increases in overall body fat and limb fat among those receiving rosiglitazone vs. the placebo group.

Which Study Is True?

Granted, the second study was so small that some percentage of the improvement in the rosiglitazone group could have occurred by chance. There were, however, several important differences between the people who participated in the second study compared to those in the larger study.

First, having a high level of insulin resistance was a requirement to enter the small study. This was not true in the large study. Therefore, it is possible that insulin resistance was more of a factor in the lipodystrophy among those in the smaller study. When insulin resistance improved, so too did the lipodystrophy. Also, the use of stavudine, which is strongly associated with lipoatrophy, was higher among those receiving rosiglitazone compared to those in the placebo arm of the larger study. Lastly, 25% of those in the small study were women, compared to only 2% of those in the larger study. Each of these factors could have played a role in the differing results.

Avoiding the use of anti-HIV drugs associated with lipoatrophy, like stavudine, can help prevent it and lead to at least some improvements in those who've already lost fat. However, anti-HIV drugs are only one factor with lipoatrophy and much is still unknown. Other than the glitazone drugs, there are few promising treatments being researched for lipoatrophy. Thus, despite the mixed results of studies so far, and the side effects and drug interactions associated with both rosiglitazone and pioglitazone, further research must continue.

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