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

TitleEffects of metformin and rosiglitazone in HIV-infected patients with hyperinsulinemia and elevated waist/hip ratio.
Publication TypeJournal Article
Year of Publication2007
AuthorsMulligan K, Yang Y, Wininger DA, Koletar SL, Parker RA, Alston-Smith BL, Schouten JT, Fielding RA, Basar MT, Grinspoon S
JournalAIDS
Volume21
Issue1
Pagination47-57
Date Published2007 Jan 2
ISSN0269-9370
KeywordsAdult, Body Composition, Drug Administration Schedule, Drug Therapy, Combination, Female, HIV Infections, Humans, Hyperinsulinism, Hypoglycemic Agents, Lipids, Male, Metformin, Middle Aged, Statistics, Nonparametric, Thiazolidinediones, Treatment Outcome, 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.

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

DOI10.1097/QAD.0b013e328011220e
Alternate JournalAIDS
PubMed ID17148967
Grant ListAI027666 / AI / NIAID NIH HHS / United States
AI032783 / AI / NIAID NIH HHS / United States
AI25859 / AI / NIAID NIH HHS / United States
AI25897 / AI / NIAID NIH HHS / United States
AI25903 / AI / NIAID NIH HHS / United States
AI25915 / AI / NIAID NIH HHS / United States
AI25924 / AI / NIAID NIH HHS / United States
AI27659 / AI / NIAID NIH HHS / United States
AI27660 / AI / NIAID NIH HHS / United States
AI27661 / AI / NIAID NIH HHS / United States
AI27663 / AI / NIAID NIH HHS / United States
AI27664 / AI / NIAID NIH HHS / United States
AI27665 / AI / NIAID NIH HHS / United States
AI27668 / AI / NIAID NIH HHS / United States
AI27670 / AI / NIAID NIH HHS / United States
AI27673 / AI / NIAID NIH HHS / United States
AI34853 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI46339 / AI / NIAID NIH HHS / United States
AI46370 / AI / NIAID NIH HHS / United States
RR00052 / RR / NCRR NIH HHS / United States
RR000750 / RR / NCRR NIH HHS / United States
RR00083 / RR / NCRR NIH HHS / United States
RR00096 / RR / NCRR NIH HHS / United States