Short-term metabolic and cardiovascular effects of metformin in markedly obese adolescents with normal glucose tolerance
Article first published online: 27 AUG 2008
© 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard
Volume 9, Issue 6, pages 567–576, December 2008
How to Cite
Burgert, T. S., Duran, E. J., Goldberg-Gell, R., Dziura, J., Yeckel, C. W., Katz, S., Tamborlane, W. V. and Caprio, S. (2008), Short-term metabolic and cardiovascular effects of metformin in markedly obese adolescents with normal glucose tolerance. Pediatric Diabetes, 9: 567–576. doi: 10.1111/j.1399-5448.2008.00434.x
- Issue published online: 18 NOV 2008
- Article first published online: 27 AUG 2008
- Submitted 15 January 2008. Accepted for publication 23 May 2008
- body fat distribution;
- heart rate recovery;
Objective: Although metformin (MET) is an insulin sensitizer currently used as an adjunct to the treatment of some of the complications of childhood obesity besides type 2 diabetes mellitus, few studies have comprehensively examined its metabolic and clinical effects in obese children with normal glucose tolerance (NGT).
Methods: We therefore conducted a 4-month double-blind clinical trial in 28 obese [mean body mass index (BMI): 40.3 ± 5.7 kg/m2], insulin-resistant [homeostasis model assessment – insulin resistance: 7.6 ± 2.8 and whole body insulin sensitivity index (WBISI): 1.5 ± 0.7] adolescents (age 15.0 ± 1.3 yr) randomized to MET (n = 15, dose 1500 mg daily) or placebo (n = 13).
Results: The treatment with MET was well tolerated. MET treatment was associated with a decreased BMI (p = 0.02) as well as with a reduction in subcutaneous fat (p = 0.03), particularly the deep subcutaneous fat (p = 0.04) as assessed by magnetic resonance imaging. Postintervention, the MET group had a 35% improvement in insulin sensitivity (WBISI) compared with the placebo group (p = 0.008). However, significance was lost with adjustments for differences in baseline insulin sensitivity (p = 0.09). While there was no change in inflammatory cytokines or lipid parameters, cardiovascular function as assessed by heart rate recovery after exercise improved with MET and worsened in placebo (p = 0.03).
Conclusion: Short-term use of MET is well tolerated by obese children with NGT and has a beneficial effect on BMI and autonomic control of the heart as well as a trend toward improved insulin sensitivity. Thus, long-term treatment with MET may provide a means to ameliorate the cardio-metabolic consequences of adolescent obesity.