Rosiglitazone significantly increases triglyceride and cholesterol levels and does not improve HAART-associated lipoatrophy
HAART is associated with metabolic adverse events such as insulin resistance and lipodystrophy, that is, atrophy of subcutaneous fat and/or accumulation of intra-abdominal fat. Currently, there is no pharmacological treatment for lipoatrophy (fat loss).
Glitazones, a novel class of insulin-sensitising anti-diabetic agents, increase subcutaneous fat in patients with type 2 diabetes. There are no controlled studies of glitazones in patients with HAART-associated lipodystrophy (HAL).
In this randomised, double-blind, placebo-controlled study, conducted by researchers at the Helsinki University Central Hospital, Helsinki, Finland, 30 patients with HAL received either rosiglitazone (8 mg daily) or placebo for 24 weeks.
Baseline characteristics were compared to a group of 30 age-, sex- and weight-matched HIV-negative controls. At baseline, patients with HAL had 1.8-fold (P<0.001) more intra-abdominal and 2.4-fold (P<0.05) more liver fat than HIV-negative controls, who had 1.8-fold (P<0.001) more subcutaneous fat than the patients.
After 24 weeks of treatment, rosiglitazone had no effect on body weight, subcutaneous or intra-abdominal fat (magnetic resonance imaging), total body fat (bioimpedance analysis), anthropometric measurements or serum leptin concentrations (a circulating marker of adipose tissue mass).
However, rosiglitazone decreased % liver fat (spectroscopy) and serum insulin concentrations, and normalised liver function tests.
During the first 12 weeks of rosiglitazone treatment, serum triglycerides increased from 3.5 +/- 0.5 to 6.5 +/- 2.0 mmol/l (from 310 +/- 44 to 575 +/- 177 mg/dl) (P<0.05) and serum cholesterol from 6.0 +/- 0.4 to 7.8 +/- 0.7 mmol/l (from 232 +/- 15 to 301 +/- 27 mg/dl) (P<0.01).
The authors conclude: “Contrary to data in other patient groups, rosiglitazone did not increase subcutaneous fat in patients with HAL after 24 weeks of treatment. Rosiglitazone seemed to ameliorate insulin resistance judged by the decreased serum insulin concentrations and % liver fat.”
“Rosiglitazone unexpectedly caused significant increases in serum triglyceride and cholesterol concentrations, which must be carefully monitored if glitazones are used in these patients.”
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.
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