The diabetes drug rosiglitazone does not significantly improve fat loss or blood lipids in antiretroviral-treated individuals with lipodystrophy, according to a Canadian study published in the June 15th edition of the Journal of Infectious Diseases.
However, the author of an editorial accompanying the study noted that use of rosiglitazone did lead to a modest improvement in body fat in the lower limbs in some patients and that rosiglitazone and other drugs from the thiazolidinediones class of diabetes drugs could have a role in the treatment of patients with fat loss who also have diabetes.
A recently published meta-analysis of studies involving rosiglitazone found that its use was associated with an increased risk of heart disease. Interestingly, the editorial accompanying the Canadian study, which went to press months before the meta-analysis was published, notes that use of rosiglitazone should be avoided by patients who are overweight or who have heart problems.
Rosiglitazone is widely used for the treatment of diabetes, but its use has also been studied as a treatment for body fat changes in HIV-positive individuals taking antiretroviral therapy.
Between 2002 and 2004 Canadian investigators conducted a randomised, placebo-controlled trial involving 78 HIV-positive individuals taking a protease inhibitor-based antiretroviral regimen who had body fat changes. The patients were randomised to receive a 4mg daily dose of rosiglitazone or a placebo. The primary outcome was changes in upper limb fat assessed using DEXA scans after 24 weeks of treatment. Secondary outcomes of the study were changes in levels of blood fats and sugars, and changes in other body measurements.
It was originally intended to recruit over 252 patients to the study in order to ensure that there was enough statistical power to detect meaningful changes in body fat between the two arms of the study. However, a number of factors made it difficult to enrol patients to the trial and recruitment was stopped early. One of the issues affecting recruitment was an outbreak of SARS in Toronto. Another was the recognition that d4T (stavudine, Zerit) and to a less extent, AZT (zidovudine), are causes of fat loss, and a consequent reduction in the prescription of these drugs.
The patients had a median age of 47 years, 97% were men, the median duration of antiretroviral therapy was eight years, and 54% were taking d4T or AZT.
After 24 weeks of treatment, arm fat, the primary outcome of the study, was not significantly different between the two arms of the study. Nor were there any significant differences between the two treatment groups regarding leg fat, limb fat, trunk fat, or total body fat.
Furthermore, there were no significant differences in total cholesterol, triglycerides, HDL cholesterol, serum glucose levels, or indicators of insulin resistance between the two arms of the study.
There was further confirmation that d4T and AZT are implicated in fat loss as rosiglitazone-treated patients who were not taking these drugs experienced fat gain, but these gains were not statistically significant.
Adverse events were experienced by 33 (85%) of the patients in the rosiglitazone arm, but only eleven (14%) of these were thought to be related to the drug.
“Our study failed to demonstrate an impact of 24 weeks of rosiglitazone on lipoatrophy, when compared with placebo”, write the investigators.
However, the author of an accompanying editorial notes that patients in the study who took rosiglitazone were protected from further fat loss from the limbs compared to patients in the placebo arm. The author also notes that the study was statistically under-powered.
The author sees a possible role for the use of rosiglitazone, and other drugs from the thiazolidinediones class for the treatment of HIV-positive individuals, who are taking antiretroviral therapy and who have type two diabetes and fat loss. The author also writes that thiazolidinediones are “best avoided” in patients who are overweight and who have heart failure.”
Cavalcanti RB et al. A randomized, placebo-controlled trial of rosiglitazone for HIV-related lipoatrophy. J Infect Dis 195: 1754 – 1761, 2007.
Grinspoon S et al. Use of thiazolidinediones in HIV-infected patients: what have we learned. J Infect Dis 195: 1731 – 1733, 2007.