Effects of Growth Hormone and Pioglitazone in Viscerally Obese Adults with Impaired Glucose Tolerance: A Factorial Clinical Trial

OBJECTIVE: Recombinant human growth hormone (GH) and pioglitazone (PIO) in abdominally obese adults with impaired glucose tolerance were evaluated under the hypothesis that the combination attenuates GH-induced increases in glucose concentrations, reduces visceral adipose tissue (VAT), and improves insulin sensitivity over time. DESIGN: Randomized, double-blind, placebo-controlled, 2 × 2 factorial design. SETTING: Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States. PARTICIPANTS: 62 abdominally obese adults aged 40–75 with impaired glucose tolerance. INTERVENTIONS: GH (8 μg/kg/d, or placebo) and pioglitazone (30 mg/d, or placebo) for 40 wk. OUTCOME MEASURES: Baseline and after 40 wk of treatment, VAT content was quantified by CT scan, glucose tolerance was assessed using a 75-g oral glucose tolerance test, and insulin sensitivity was measured using steady-state plasma glucose levels obtained during insulin suppression test. RESULTS: Baseline: body mass index (BMI), plasma glucose, and visceral fat content were similar. 40 wk: visceral fat area declined 23.9 ± 7.4 cm(2) in GH group, mean difference from placebo: −28.1 cm(2) (95% CI −49.9 to −6.3 cm(2); p = 0.02). Insulin resistance declined 52 ± 11.8 mg/dl with PIO, mean difference from placebo of −58.8 mg/dl (95% CI −99.7 to −18.0 mg/dl; p = 0.01). VAT and SSPG declined with GH and PIO combined, mean differences from placebo of −31.4 cm(2) (95% CI −56.5 cm(2) to −6.3 cm(2); p = 0.02) and −55.3 mg/dl (95% CI −103.9 to −6.7 mg/dl; p = 0.02), respectively. Fasting plasma glucose increased transiently in GH group. No significant changes in BMI were observed. CONCLUSIONS: Addition of PIO to GH attenuated the short-term diabetogenic effect of GH; the drug combination reduced VAT and insulin resistance over time. GH plus PIO may have added benefit on body composition and insulin sensitivity in the metabolic syndrome.