Pioglitazone reduces peripheral lipoatrophy and improves adipokines without reducing visceral fat
9 October 2006. Related: Conference reports, Side effects, Lipodystrophy and metabolic complications, Lipodystrophy Workshop (IWADRW) 8th San Francisco 2006.
Simon Collins, HIV i-Base
Jacqueline Capeau from Pierre and Marie Curie University and colleagues presented additional results from a French study showing benefits of pioglitazone, a thiazolidinedione, on peripheral fat loss and circulating adipokines. [1] The main results from this study were presented at the Retrovirus conference in February 2006. [2]
Although previous studies with rosiglitazone were widely reported for lack of benefit [3], these were largely confounded by continued use of thymidine analogues, which blocked the likely mechanism of action. [4]
In this study, 130 HIV-positive patients with lipodystrophy were randomised to 30mg pioglitazone once-daily or matching placebo. At 48 weeks, patients uusing pioglitazone (who were not using d4T) showed a mean increase of +0.45kg limb fat by DEXA compared to no change in the placebo arm.
Subcutaneous (SAT) and visceral adipose tissue (VAT) increased significantly but there was no significant differences between the two groups. Anthropometry measurements showed the increase in weight in pioglitazone patients (+1.7kg) was distributed mainly in increased thigh and arm circumference: thigh +1.4cm (vs 0.2cm, p=0.017), and tripcepal skin fold =0.9cm (vs 0.4cm, p=0.047).
No change occurred in glycemic parameters, triglycerides, total cholesterol or LDL cholesterol. However, HDL significantly increased (+0.09, SD 0.18 vs -0.08 mmol/L, SD 0.66 , p=0.0005). New data from this study presented at the workshop related to changes in adipokine expression. Plasma adiponectin increased from 3.9 (SD 3.3) to 8.7 (SD 7.7) in the pioglitazone arm compared to no change in placebo (P<0.0001). However, no changes were seen in plasma leptin, resistin and soluble TNF-alpha receptor.
The change in limb fat correlated with both pioglitazone concentration (r=0.476, P<0.001) and leptin variation (r=0.365, P<0.01).
These results support the use of pioglitazone in the treatment of lipoatrophy in patients with HIV-related lipoatrophy who are no longer using thymidine analogues in their regimen.
References:
- Maachi M, Slama L, Capeau J et al. Effect of pioglitazone on limb fat and circulating adipokines in HIV-related lipodystrophy (ANRS113:Lipiot). 8th IWADRLH, September 2006, San Francisco. Abstract 23.
- Slama L, Lanoy E, Valentin MA et al. Effect of Pioglitazone on HIV-1 Related Lipoatrophy: a Randomized Double-Blind Placebo-Controlled Trial (ANRS 113) with 130 patients. 13th CROI, 2006. Late breaker abstract 151LB. See HTB March 2006.
http://www.i-base.info/htb/3011 - Carr A, Workman C, Carey D, et al. No effect of rosiglitazone for treatment of HIV-1 lipoatrophy: randomised, double-blind, placebo-controlled trial. Lancet. 2004 Feb 7;363(9407):4 29-38.
- Mallon P, Unemori P, Bowen M, et al. Nucleoside reverse transcriptase inhibitors decrease mitochondrial and PPAR-gamma gene expression in adipose tissue after only 2 weeks in HIV-uninfected healthy adults. 11th CROI, 2004. Abstract 76.