BACKGROUND:Insulin resistance increases during adolescence in those with type 1 diabetes mellitus (T1DM), complicating glycemic control and potentially increasing cardiovascular disease (CVD) risk. Metformin, typically used in type 2 diabetes mellitus (T2DM), is a possible adjunct therapy in T1DM to help improve glycemic control and insulin sensitivity. OBJECTIVE: We hypothesized that metformin would improve metabolic parameters in adolescents with T1DM. DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blinded, placebo-controlled trial included 74 pubertal adolescents (ages: 13-20 yr) with T1DM. Participants were randomized to receive either metformin or placebo for 6 months. Glycated hemoglobin (HbA1c), insulin dose, waist circumference, body mass index (BMI), andblood pressure were measured at baseline, 3 and 6 months, with fasting lipids measured at baseline and 6 months. RESULTS:Total daily insulin dose, BMI z-score and waist circumference significantly decreased at 3 and 6 months compared to baseline within the metformin group, even among normal-weight participants. In the placebo group, total insulin dose and systolic blood pressure increased significantly at 3 months and total insulin dose increased significantly at 6 months. No significant change was observed in HbA1c at any time point between metformin and placebo groups or within either group. CONCLUSIONS: Low-dose metformin likely improves BMI as well as insulin sensitivity in T1DM adolescents, as indicated by a decrease in total daily insulin dose. The decrease in waist circumference indicates that fat distribution is also likely impacted by metformin in T1DM. Further studies with higher metformin doses and more detailed measurements are needed to confirm these results, their underlying mechanisms, and potential impact on CVD in T1DM youth.
RCT Entities:
BACKGROUND:Insulin resistance increases during adolescence in those with type 1 diabetes mellitus (T1DM), complicating glycemic control and potentially increasing cardiovascular disease (CVD) risk. Metformin, typically used in type 2 diabetes mellitus (T2DM), is a possible adjunct therapy in T1DM to help improve glycemic control and insulin sensitivity. OBJECTIVE: We hypothesized that metformin would improve metabolic parameters in adolescents with T1DM. DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blinded, placebo-controlled trial included 74 pubertal adolescents (ages: 13-20 yr) with T1DM. Participants were randomized to receive either metformin or placebo for 6 months. Glycated hemoglobin (HbA1c), insulin dose, waist circumference, body mass index (BMI), and blood pressure were measured at baseline, 3 and 6 months, with fasting lipids measured at baseline and 6 months. RESULTS: Total daily insulin dose, BMI z-score and waist circumference significantly decreased at 3 and 6 months compared to baseline within the metformin group, even among normal-weight participants. In the placebo group, total insulin dose and systolic blood pressure increased significantly at 3 months and total insulin dose increased significantly at 6 months. No significant change was observed in HbA1c at any time point between metformin and placebo groups or within either group. CONCLUSIONS: Low-dose metformin likely improves BMI as well as insulin sensitivity in T1DM adolescents, as indicated by a decrease in total daily insulin dose. The decrease in waist circumference indicates that fat distribution is also likely impacted by metformin in T1DM. Further studies with higher metformin doses and more detailed measurements are needed to confirm these results, their underlying mechanisms, and potential impact on CVD in T1DM youth.
Authors: Ricardo Gómez; Moinuddin H Mokhashi; Jayashree Rao; Alfonso Vargas; Terry Compton; Robert McCarter; Stuart A Chalew Journal: J Pediatr Endocrinol Metab Date: 2002 Sep-Oct Impact factor: 1.634
Authors: Ingrid M Libman; Massimo Pietropaolo; Silva A Arslanian; Ronald E LaPorte; Dorothy J Becker Journal: Diabetes Care Date: 2003-10 Impact factor: 19.112
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Authors: Melanie Cree-Green; Bryan C Bergman; Eda Cengiz; Larry A Fox; Tamara S Hannon; Kellee Miller; Brandon Nathan; Laura Pyle; Darcy Kahn; Michael Tansey; Eileen Tichy; Eva Tsalikian; Ingrid Libman; Kristen J Nadeau Journal: J Clin Endocrinol Metab Date: 2019-08-01 Impact factor: 5.958
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Authors: S Fazeli Farsani; P C Souverein; J A Overbeek; M M J van der Vorst; C A J Knibbe; R M C Herings; A de Boer; A K Mantel-Teeuwisse Journal: Br J Clin Pharmacol Date: 2015-05-20 Impact factor: 4.335