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Horm Metab Res 2004; 36(1): 54-61
DOI: 10.1055/s-2004-814199
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Effects of a Combination of Recombinant Human Growth Hormone with Metformin on Glucose Metabolism and Body Composition in Patients with Metabolic Syndrome

B.  L.  Herrmann1 , C.  Berg1 , E.  Vogel1 , T.  Nowak2 , K.  Renzing-Koehler3 , K.  Mann1 , B.  Saller1, 2
  • 1Division of Endocrinology, University of Essen, Germany
  • 2Pharmacia GmbH, Erlangen, Germany
  • 3Institute for Medical Informatics, Biometry and Epidemiology, University of Essen, Germany
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Publication History

Received 10 June 2003

Accepted after revision 18 August 2003

Publication Date:
25 February 2004 (online)

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Abstract

Abdominal obesity and insulin resistance are central findings in metabolic syndrome. Since treatment with recombinant human growth hormone (rhGH) can reduce body fat mass in patients with organic GH deficiency, rhGH therapy may also have favourable effects on patients with metabolic syndrome. However, due to the highly increased risk for type 2 diabetes in these patients, strategies are needed to reduce the antagonistic effect of rhGH against insulin. We conducted a 18-month randomised, double-blind, placebo-controlled study to assess the effect of rhGH in combination with metformin (Met) in patients with metabolic syndrome. 25 obese men (55 ± 6 years, BMI 33.4 ± 2.9 kg/m2) with mildly elevated fasting plasma glucose (FPG) levels at screening (6.1 - 8.0 mmol/l) were included. All patients received metformin (850 mg twice daily) either alone or in combination with rhGH (daily dose 9.5 μg/kg body weight). An oGTT was performed at baseline, after 6 weeks, and after 3, 6, 12, and 18 months of therapy. Glucose disposal rate (GDR) was measured by euglycemic hyperinsulinemic clamp at 0 and 18 months and body composition was measured by DEXA every 6 months. In the Met + GH group, IGF-I increased from 146 ± 56 μg/l to 373 ± 111 μg/l (mean ± SD) after 3 months and remained stable after that. BMI did not change significantly in either group during the study. Total body fat decreased by -4.3 ± 5.4 kg in the Met + GH group and by -2.7 ± 2.9 kg in the Met + Placebo group (differences between the two groups: p = n. s.). Waist circumference decreased in both groups (Met + GH: 118 ± 8 cm at baseline, 112 ± 10 cm after 18 months; Met + Placebo: 114 ± 7 cm vs. 109 ± 8 cm; differences between the two groups: p = 0.096). In the Met + GH group, FPG increased significantly after 6 months (5.9 ± 0.7 vs. 6.7 ± 0.4 mmol/l; p = 0.005), but subsequently decreased to baseline levels (18 months: 5.8 ± 0.2 mmol/l). FPG remained stable in the Met + Placebo group until 12 months had elapsed, and then slightly decreased (baseline: 6.2 ± 0.3, 18 months: 5.5 ± 0.6 mmol/l, p = 0.02). No significant changes were seen in either group regarding glucose and insulin AUC during oGTT or HbA1c levels. GDR at 18 months increased by 20 ± 39 % in Met + GH-group and decreased by -11 ± 25 % in the Met + Placebo group (differences between the two groups: p = 0.07). In conclusion, treatment of patients with metabolic syndrome and elevated FPG levels did not cause sustained negative effects on glucose metabolism or insulin sensitivity if given in combination with metformin. However, since our data did not show significant differences between the two treatment groups with respect to body composition or lipid metabolism, future studies including larger numbers of patients will have to clarify whether the positive effects of rhGH on cardiovascular risk factors that have been shown in patients with GH deficiency are also present in patients with metabolic syndrome, and are additive to the effects of metformin.

Key words

Growth hormone - Metformin - Metabolic syndrome

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B. L. Herrmann, M. D.

Division of Endocrinology · Centre of Internal Medicine · University of Essen ·

Hufelandstr. 55 · 45122 Essen · Germany

Phone: +49(201)7232821

Fax: +49(2017235972 ·

Email: burkhard.herrmann@uni-essen.de