title: Effects of metformin and rosiglitazone in HIV-infected patients with hyperinsulinemia and elevated waist/hip ratio.
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.
  
  
  CONCLUSIONS
  Both treatments improved insulin sensitivity, but neither reduced visceral fat. Rosiglitazone may increase subcutaneous fat in some individuals.
authors.affiliation: University of California at San Francisco, San Francisco General Hospital, San Francisco, California, USA. kmulligan@sfghgcrc.ucsf.edu
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mulligan
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: David A
authors.initials: DA
authors.lastname: Wininger
authors.forename: Susan L
authors.initials: SL
authors.lastname: Koletar
authors.forename: Robert A
authors.initials: RA
authors.lastname: Parker
authors.forename: Beverly L
authors.initials: BL
authors.lastname: Alston-Smith
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Schouten
authors.forename: Roger A
authors.initials: RA
authors.lastname: Fielding
authors.forename: Michael T
authors.initials: MT
authors.lastname: Basar
authors.forename: Steven
authors.initials: S
authors.lastname: Grinspoon
mesh_terms: D000328:Adult; D001823:Body Composition / Q000187:drug effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D000077154:Rosiglitazone; D018709:Statistics, Nonparametric; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D049629:Waist-Hip Ratio
chemical_list: D007004:Hypoglycemic Agents; D008055:Lipids; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin