Rosiglitazone shows no benefit for lipoatrophy
Simon Collins, HIV i-Base
Several research groups have already reported that rosiglitazone (RSG) is not an effective agent to treat lipoatrophy, [2, 3] and this was confirmed in an oral presentation of a new study from Andrew Carr. 
This study randomised 108 patients with lipoatrophy to either 4mg rosiglitazone twice-daily (n=53) or placebo (n=55) for 48 weeks. The study was powered to detect a 0.5kg difference in limb fat by DEXA scan.
Limb fat increased by 0.14 kg in the RSG group and 0.18 kg in the placebo group (mean difference, -0.04 [95%CI, -0.29, 0.21] kg; p= 0.74 by rank-sum test). There was no benefit of RSG on: subcutaneous thigh or abdominal fat, or visceral fat or objective or subjective assessment of lipodystrophy severity (p= 0.99 and p= 0.42 respectively).
There were significant increases in plasma adiponectin (4.1 mmol/L [101%]; p<0.0001), which was the theoretical rationale behind the study, but not leptin (0.2 mmol/L [6%]; p= 0.33), and significant (p= 0.01 – 0.02) decreases in three markers of insulin resistance with RSG. No subgroup, defined by PI use, thymidine NRTI use, limb fat mass, or insulin resistance at baseline, derived benefit for limb fat with RSG.
The key adverse effects of RSG were asymptomatic hypertriglyceridaemia (mean peak increase, 1.5 mmol/L [58 mg/dL; 40%] at week 8; +0.9 mmol/L [35 mg/dL] at week 48; p=0.007) and hypercholesterolaemia (mean peak increase 1.9 mmol/L [170 mg/dL] at week 8; +1.5 mmol/L [132 mg/dL; 16%] at week 48; p= 0.0001). There was no significant effect on viral load or CD4 counts.
Previous studies showing that rosiglitazone does not improve lipoatrophy, even at higher doses than used in this study, were presented at the 5th International Workshop on Lipodystrophy in Paris last year, and at the Retrovirus Conference in 2002. [2, 3]
These results are in contrast to data reported from non-HIV associated lipodystrophy and NIDDM type-2 patients from glitazones. These patients showed a partial reversal of central fat accumulation and in the first group a trend for an increase in subcutaneous fat. Dyslipidemia in this study seems to be the same as reported from patients with diabetes mellitus type-2.
In March 2003, a study published in AIDS showed some return of fat with pioglitazone, which also did not increase cholesterol or triglycerides. However this was an uncontrolled case study in 11 patients which limits the conclusions to be drawn from this study. Takeda, the manufacturer of pioglitazone, apparently has no interest in HIV and because of this the data are limited. 
- Carr A, Workman C, Rogers G et al. Rosiglitazone for the treatment of HIV lipoatrophy: a double-blind, placebo-controlled, 48-week trial. 11th CROI 2004, Oral abstract 79.
- Hadigan C, Yawetz S, Thomas A et al – A randomised, double-blind, placebo-controlled study of rosiglitazone for patients with HIV lipodystrophy. 9th CROI 2002. Abstract 12.
- Sutinen J et al. Rosiglitazone in the treatment of HAART-associated lipodystrophy – a randomised double-blind placebo-controlled study. Antiviral Therapy 8(3): 199-207. June 2003.
- Calmy A, Hirschel B, Didier H et al. Glitazones in lipodystrophy syndrome induced by highly active antiretroviral therapy. AIDS. 17(5):770-772, March 28, 2003.