Diazoxide in Children With Obesity After Hypothalamic-Pituitary Lesions: A Randomized, Placebo-Controlled Trial.
The objective was to evaluate the safety and efficacy of diazoxide (DZX) for decreasing obesity with hyperinsulinemia in patients treated for hypothalamic-pituitary lesions during childhood.



This was a double-blind, placebo-controlled trial in parallel groups using a centralized randomization process (PEDIAC).



This was a single-center study.



Among the 40 patients included, 35 fulfilled the study requirements.



Interventions included six-month treatment with DZX (4 mg/kg/d) or placebo.



The primary outcome was relative weight change at 2 months. Secondary outcomes were changes in absolute weight, plasma insulin concentrations, glucose peak after oral glucose tolerance test (OGTT), and glycosylated hemoglobin after 2 months.



Eighteen participants were randomized to the DZX group; three withdrew their consent or were excluded after the occurrence of diabetes mellitus at days 10, 10, and 35, respectively; and two dropped out because of protocol non-compliance at day 10. No statistically significant differences in baseline characteristics were observed among the 13 DZX patients and the 17 placebo patients. The relative weight changes at 2 months in the DZX and placebo groups were -0.9 and -0.5%, respectively (P = nonsignificant). No statistically significant differences were observed between the groups concerning the change in absolute weight or glycosylated hemoglobin after 2 months, but the plasma glucose concentrations (basal and after OGTT) were significantly greater in the patients receiving DZX treatment vs those receiving the placebo, whereas the plasma increases in insulin after OGTT were lower.



The 2-month treatment with DZX was not associated with a significant change in weight compared with placebo; however, it was associated with the occurrence of diabetes mellitus in three of 18 patients.
Université Paris Descartes and Fondation Ophtalmologique Adolphe de Rothschild (R.B., M.P., S.G.), Unité d'Endocrinologie Pédiatrique, Paris 75940, France; Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (R.S., J.-M.T.), Unité de Recherche Clinique Paris Cochin-Necker, Paris 75743, France; Assistance Publique-Hôpitaux de Paris (J.-C.S.), Hôpital Necker-Enfants Malades, Service d'Explorations Fonctionnelles, Paris 75743, France; Institut Médico-Educatif Armonia (C.R.), Limeil-Brévannes 94450, France; and Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (M.Z., C.S.-R.), Hôpital Necker-Enfants Malades, Service de Neurochirurgie Pédiatrique, Paris 75743, France.
Raja
R
Brauner
Université Paris Descartes and Fondation Ophtalmologique Adolphe de Rothschild (R.B., M.P., S.G.), Unité d'Endocrinologie Pédiatrique, Paris 75940, France; Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (R.S., J.-M.T.), Unité de Recherche Clinique Paris Cochin-Necker, Paris 75743, France; Assistance Publique-Hôpitaux de Paris (J.-C.S.), Hôpital Necker-Enfants Malades, Service d'Explorations Fonctionnelles, Paris 75743, France; Institut Médico-Educatif Armonia (C.R.), Limeil-Brévannes 94450, France; and Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (M.Z., C.S.-R.), Hôpital Necker-Enfants Malades, Service de Neurochirurgie Pédiatrique, Paris 75743, France.
Raphaël
R
Serreau
Université Paris Descartes and Fondation Ophtalmologique Adolphe de Rothschild (R.B., M.P., S.G.), Unité d'Endocrinologie Pédiatrique, Paris 75940, France; Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (R.S., J.-M.T.), Unité de Recherche Clinique Paris Cochin-Necker, Paris 75743, France; Assistance Publique-Hôpitaux de Paris (J.-C.S.), Hôpital Necker-Enfants Malades, Service d'Explorations Fonctionnelles, Paris 75743, France; Institut Médico-Educatif Armonia (C.R.), Limeil-Brévannes 94450, France; and Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (M.Z., C.S.-R.), Hôpital Necker-Enfants Malades, Service de Neurochirurgie Pédiatrique, Paris 75743, France.
Jean-Claude
JC
Souberbielle
Université Paris Descartes and Fondation Ophtalmologique Adolphe de Rothschild (R.B., M.P., S.G.), Unité d'Endocrinologie Pédiatrique, Paris 75940, France; Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (R.S., J.-M.T.), Unité de Recherche Clinique Paris Cochin-Necker, Paris 75743, France; Assistance Publique-Hôpitaux de Paris (J.-C.S.), Hôpital Necker-Enfants Malades, Service d'Explorations Fonctionnelles, Paris 75743, France; Institut Médico-Educatif Armonia (C.R.), Limeil-Brévannes 94450, France; and Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (M.Z., C.S.-R.), Hôpital Necker-Enfants Malades, Service de Neurochirurgie Pédiatrique, Paris 75743, France.
Monique
M
Pouillot
Université Paris Descartes and Fondation Ophtalmologique Adolphe de Rothschild (R.B., M.P., S.G.), Unité d'Endocrinologie Pédiatrique, Paris 75940, France; Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (R.S., J.-M.T.), Unité de Recherche Clinique Paris Cochin-Necker, Paris 75743, France; Assistance Publique-Hôpitaux de Paris (J.-C.S.), Hôpital Necker-Enfants Malades, Service d'Explorations Fonctionnelles, Paris 75743, France; Institut Médico-Educatif Armonia (C.R.), Limeil-Brévannes 94450, France; and Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (M.Z., C.S.-R.), Hôpital Necker-Enfants Malades, Service de Neurochirurgie Pédiatrique, Paris 75743, France.
Sophie
S
Grouazel
Université Paris Descartes and Fondation Ophtalmologique Adolphe de Rothschild (R.B., M.P., S.G.), Unité d'Endocrinologie Pédiatrique, Paris 75940, France; Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (R.S., J.-M.T.), Unité de Recherche Clinique Paris Cochin-Necker, Paris 75743, France; Assistance Publique-Hôpitaux de Paris (J.-C.S.), Hôpital Necker-Enfants Malades, Service d'Explorations Fonctionnelles, Paris 75743, France; Institut Médico-Educatif Armonia (C.R.), Limeil-Brévannes 94450, France; and Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (M.Z., C.S.-R.), Hôpital Necker-Enfants Malades, Service de Neurochirurgie Pédiatrique, Paris 75743, France.
Christophe
C
Recasens
Université Paris Descartes and Fondation Ophtalmologique Adolphe de Rothschild (R.B., M.P., S.G.), Unité d'Endocrinologie Pédiatrique, Paris 75940, France; Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (R.S., J.-M.T.), Unité de Recherche Clinique Paris Cochin-Necker, Paris 75743, France; Assistance Publique-Hôpitaux de Paris (J.-C.S.), Hôpital Necker-Enfants Malades, Service d'Explorations Fonctionnelles, Paris 75743, France; Institut Médico-Educatif Armonia (C.R.), Limeil-Brévannes 94450, France; and Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (M.Z., C.S.-R.), Hôpital Necker-Enfants Malades, Service de Neurochirurgie Pédiatrique, Paris 75743, France.
Michel
M
Zerah
Université Paris Descartes and Fondation Ophtalmologique Adolphe de Rothschild (R.B., M.P., S.G.), Unité d'Endocrinologie Pédiatrique, Paris 75940, France; Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (R.S., J.-M.T.), Unité de Recherche Clinique Paris Cochin-Necker, Paris 75743, France; Assistance Publique-Hôpitaux de Paris (J.-C.S.), Hôpital Necker-Enfants Malades, Service d'Explorations Fonctionnelles, Paris 75743, France; Institut Médico-Educatif Armonia (C.R.), Limeil-Brévannes 94450, France; and Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (M.Z., C.S.-R.), Hôpital Necker-Enfants Malades, Service de Neurochirurgie Pédiatrique, Paris 75743, France.
Christian
C
Sainte-Rose
Université Paris Descartes and Fondation Ophtalmologique Adolphe de Rothschild (R.B., M.P., S.G.), Unité d'Endocrinologie Pédiatrique, Paris 75940, France; Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (R.S., J.-M.T.), Unité de Recherche Clinique Paris Cochin-Necker, Paris 75743, France; Assistance Publique-Hôpitaux de Paris (J.-C.S.), Hôpital Necker-Enfants Malades, Service d'Explorations Fonctionnelles, Paris 75743, France; Institut Médico-Educatif Armonia (C.R.), Limeil-Brévannes 94450, France; and Université Paris Descartes and Assistance Publique-Hôpitaux de Paris (M.Z., C.S.-R.), Hôpital Necker-Enfants Malades, Service de Neurochirurgie Pédiatrique, Paris 75743, France.
Jean-Marc
JM
Treluyer
D000293:Adolescent; D002648:Child; D003920:Diabetes Mellitus / Q000097:blood / Q000139:chemically induced*; D003981:Diazoxide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007027:Hypothalamic Diseases / Q000150:complications*; D017063:Outcome Assessment, Health Care; D063766:Pediatric Obesity / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D010900:Pituitary Diseases / Q000150:complications
D007004:Hypoglycemic Agents; D003981:Diazoxide