Effects of metformin and rosiglitazone in HIV-infected patients with hyperinsulinemia and elevated waist/hip ratio

AIDS. 2007 Jan 2;21(1):47-57. doi: 10.1097/QAD.0b013e328011220e.

Abstract

Objective: To evaluate the effects of metformin and rosiglitazone, alone or in combination, on fat distribution, insulin sensitivity, and lipids in HIV-infected patients with insulin resistance and changes in fat distribution.

Methods: A total of 105 subjects were randomly assigned to receive metformin (500 mg twice a day increasing to 1000 mg twice a day after 2 weeks) with rosiglitazone placebo (Met/P, N = 26); rosiglitazone (4 mg/day) with metformin placebo (Rosi/P, N = 27); rosiglitazone (4 mg/day) plus metformin (500 mg twice a day increasing to 1000 mg twice a day after 2 weeks; Met/Rosi, N = 25); or dual placebo (P/P, N = 27) for 16 weeks. Efficacy assessments included oral glucose tolerance testing, abdominal computed tomography, whole-body dual-energy X-ray absorptiometry, and the measurement of fasting lipids and other biochemical indices. Safety was monitored throughout. Intent-to-treat analyses were performed using non-parametric methods.

Results: The median insulin area under the curve (AUC) decreased significantly compared with baseline in both groups randomly assigned to rosiglitazone (Rosi/P -25.7 microIU/ml, P = 0.012; Met/Rosi -17.7 microIU/ml, P = 0.002); and tended to decrease in the Met/P group (-11.1 microIU/ml, P = 0.058). The change in AUC with combination therapy was significant compared with placebo (P = 0.032). No treatment was associated with significant changes in visceral or subcutaneous abdominal fat. Leg fat increased in subjects on Rosi/P compared with placebo (+4.8 versus -8.3%, P = 0.034). Rosiglitazone, but not metformin, increased adiponectin but also increased LDL-cholesterol and decreased HDL-cholesterol. Gastrointestinal effects occurred frequently in subjects on metformin.

Conclusion: Both treatments improved insulin sensitivity, but neither reduced visceral fat. Rosiglitazone may increase subcutaneous fat in some individuals.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Composition / drug effects
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / physiopathology
  • Humans
  • Hyperinsulinism / blood
  • Hyperinsulinism / drug therapy*
  • Hyperinsulinism / virology
  • Hypoglycemic Agents / therapeutic use*
  • Lipids / blood
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Rosiglitazone
  • Statistics, Nonparametric
  • Thiazolidinediones / therapeutic use*
  • Treatment Outcome
  • Waist-Hip Ratio

Substances

  • Hypoglycemic Agents
  • Lipids
  • Thiazolidinediones
  • Rosiglitazone
  • Metformin