Y E Lentferink1, M P van der Aa1,2, E G A H van Mill3, C A J Knibbe4,5, M M J van der Vorst6. 1. Department of Pediatrics, St. Antonius Hospital, Nieuwegein/Utrecht, The Netherlands. 2. Kalkhaven, Gorinchem, The Netherlands. 3. Department of Pediatrics, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands. 4. Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein/Utrecht, The Netherlands. 5. Division of Pharmacology, LACDR, Leiden University, Leiden, The Netherlands. 6. Department of Pediatrics, St. Antonius Hospital, Nieuwegein/Utrecht, The Netherlands. m.van.der.vorst@antoniusziekenhuis.nl.
Abstract
BACKGROUND/ OBJECTIVES:Off-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin treatment in adolescents with obesity are scarce. Therefore, an 18 month open label extension study following an 18 months randomized placebo-controlled trial (RCT) on the efficacy, safety, and tolerability of metformin in adolescents with obesity and insulin resistance was performed. SUBJECTS/ METHODS: After completion of the RCT, metformin was offered to all participants with a body mass index standard deviation score (BMI-sds) > 2.3 and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) ≥ 3.4. Endpoints were change in BMI and HOMA-IR. RESULTS: Overall, 31/42 participants completed the extension study (74% girls, median age 14.8 (11.6 - 17.9), BMI 31.2 (22.3 - 45.1), HOMA-IR 3.4 (0.2 - 8.8)). At start, 22/42 (52.4%) participants were eligible for metformin of which 13 (59.0%) agreed with treatment. In participants who continued metformin, an increase was observed in BMI (+2.2 (+0.2 to +9.0)) and HOMA-IR (+13.7 (+1.6 to +48.3)). In metformin naive participants, BMI stabilized after an initial decrease (+0.5 (-2.1 to +5.1)). For HOMA-IR, a decrease was observed (-1.1 (-4.6 to +1.4)). CONCLUSION: While metformin treatment in metformin naive participants seems to result in an initial decrease in BMI and HOMA-IR, there is no evidence for sustained effect after prolonged use in adolescents. Limited compliance and/or insufficient dose may explain the differences in long-term effects between adolescents and adults.
RCT Entities:
BACKGROUND/ OBJECTIVES: Off-label metformin is nowadays frequently used for the treatment of obesity in adolescents. However, studies on long-term metformin treatment in adolescents with obesity are scarce. Therefore, an 18 month open label extension study following an 18 months randomized placebo-controlled trial (RCT) on the efficacy, safety, and tolerability of metformin in adolescents with obesity and insulin resistance was performed. SUBJECTS/ METHODS: After completion of the RCT, metformin was offered to all participants with a body mass index standard deviation score (BMI-sds) > 2.3 and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) ≥ 3.4. Endpoints were change in BMI and HOMA-IR. RESULTS: Overall, 31/42 participants completed the extension study (74% girls, median age 14.8 (11.6 - 17.9), BMI 31.2 (22.3 - 45.1), HOMA-IR 3.4 (0.2 - 8.8)). At start, 22/42 (52.4%) participants were eligible for metformin of which 13 (59.0%) agreed with treatment. In participants who continued metformin, an increase was observed in BMI (+2.2 (+0.2 to +9.0)) and HOMA-IR (+13.7 (+1.6 to +48.3)). In metformin naive participants, BMI stabilized after an initial decrease (+0.5 (-2.1 to +5.1)). For HOMA-IR, a decrease was observed (-1.1 (-4.6 to +1.4)). CONCLUSION: While metformin treatment in metformin naive participants seems to result in an initial decrease in BMI and HOMA-IR, there is no evidence for sustained effect after prolonged use in adolescents. Limited compliance and/or insufficient dose may explain the differences in long-term effects between adolescents and adults.
Authors: Tania S Burgert; Elvira J Duran; Rachel Goldberg-Gell; James Dziura; Catherine W Yeckel; Stuart Katz; William V Tamborlane; Sonia Caprio Journal: Pediatr Diabetes Date: 2008-08-27 Impact factor: 4.866
Authors: Thomas H Inge; Anita P Courcoulas; Todd M Jenkins; Marc P Michalsky; Michael A Helmrath; Mary L Brandt; Carroll M Harmon; Meg H Zeller; Mike K Chen; Stavra A Xanthakos; Mary Horlick; C Ralph Buncher Journal: N Engl J Med Date: 2015-11-06 Impact factor: 91.245
Authors: Marloes P van der Aa; Soulmaz Fazeli Farsani; Lisa A J Kromwijk; Anthonius de Boer; Catherijne A J Knibbe; Marja M J van der Vorst Journal: Clin Pediatr (Phila) Date: 2013-11-14 Impact factor: 1.168
Authors: William V Tamborlane; Morey W Haymond; David Dunger; Ravi Shankar; Rose Gubitosi-Klug; Kathleen Bethin; Janina Karres; Paolo Tomasi; Ingrid Libman; Paula H Hale; Ronald Portman; Georgeanna Klingensmith; Michael Reed; Jeffrey Blumer; George Giacoia Journal: Diabetes Care Date: 2016-03 Impact factor: 19.112