December 16, 2005
The use of highly active antiretroviral therapy (HAART), despite its many benefits, has been associated with a number of long-term side effects, including changes in body fat distribution, insulin resistance and dyslipidemia. These remain ongoing complications with few solutions.
On a purely mechanistic basis, it has been postulated that medications used for the treatment of adult-onset diabetes mellitus may be useful in reversing the insulin resistance, and perhaps the other complications of treatment. With this in mind, Van Wijk and colleagues from the Netherlands conducted a randomized study of rosiglitazone (Avandia) (n = 19) versus metformin (Glucophage, Fortamet) (n = 20) in patients who were on antiretroviral therapy with self-defined lipodystrophy. Study participants (median age 47 to 48 years, depending on the treatment group) had been HIV infected for a median of 7.5 to 8.4 years.
Both interventions led to a decrease in insulin resistance, as would be expected based on their main therapeutic indication. In the rosiglitazone group, there was an increase in adiponectin levels over 26 weeks of observation (44 to 95 mg/L). Lowered adiponectin levels have been associated with lipodystrophy, but an increase in adiponectin levels has not been clearly associated with a reversal in lipodystrophy, so it is difficult to interpret the clinical relevance of this finding, other than to say that the medication is having its predicted mechanistic effect.
The rosiglitazone led to an increase of 0.5 kg/m2 in body mass index (BMI) and a 3 kg increase in body fat, mainly in subcutaneous areas. In contrast the metformin led to a decrease of 0.4 kg/m2 in BMI and a 1.4 kg decrease in body fat.
As has been shown in previous studies, rosiglitazone led to a potentially detrimental increase in triglyceride levels (0.4 mmol/L), a fact that was not observed in trial participants who were receiving metformin. This study has now been published in the Annals of Internal Medicine (2005;143:337-346).
This study is very difficult to translate into clinical practice guidelines. For one thing, the study included only a small number of participants, and neither their antiretroviral treatment history nor their lipodystrophy or metabolic alterations were systematically defined. In addition, the results must be interpreted in the context of placebo-controlled trials of rosiglitazone that have shown it to be ineffective in this context.
This being said, data on individual patients enrolled in this study showed that a minority benefited greatly from the intervention and it may be that we will be able to identify baseline characteristics that will help predict such a response. In the meantime, the findings of this study cannot be used to generate guidelines for the use of either rosiglitazone or metformin in clinical practice.
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