ESPE Abstracts (2016) 86 P-P1-607

Effects of the Addition of Metformin to Recombinant Human GH on Bone Maturation and Pubertal Progression in Short Children Born Small-for-Gestational-Age

Mireia Tirado Capistros, Paula Casano Sancho & Lourdes Ibañez Toda


Hospital Sant Joan de Déu, Esplugues, Barcelona, Spain


Background: Small for gestational age (SGA) children who experience rapid and exaggerated postnatal catch-up are prone to develop insulin resistance and to progress faster into puberty, resulting in a shorter final height. Short, non-catch-up SGA children treated with recombinant human GH (rhGH) may present with the same sequence. In a previous controlled study from our group performed in short SGA children, metformin – added to rhGH therapy – improved endocrine-metabolic parameters without modifying the reponse to rhHG.

Objective and hypotheses: To describe the effects of the addition of metformin to rhGH in non-catch-up SGA on growth, pubertal timing and endocrine-metabolic variables.

Method: Retrospective, descriptive study in a tertiary hospital (2010–2015). Inclusion criteria: SGA children (39.5% girls) treated with rhGH only (n=18; 0.035–0.04 mg/kg per day) or with rhGH plus metformin (n=20; 23–25 mg/kg per day) with either early puberty and/or an advance in bone age >1 year in the previous 6 months.

Results: The results were analyzed after 28 months (12–55) on treatment, when patients had reached Tanner III–IV stage. At baseline, the rhGH+metformin group had higher growth velocity in the previous year and a more advanced bone age (P<0.05 vs the rhGH-only subgroup). In the rhGH+metformin subgroup, bone age progressed less in the second and third year of follow-up in comparison to the rhGH-only group (P<0.05). No differences in pubertal timing, age at menarche, growth velocity or analytical parameters were found between subgroups.

Conclusion: Despite the methodological limitations (observational, not controlled study), these preliminary results show that in those patients with higher growth velocity and an advanced bone age at puberty start, metformin slows down bone maturation, without altering growth rate. Longer follow up will ascertain whether metformin can also modulate pubertal progression and thus improve final height.

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