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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.

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