Effects of low dose metformin in adolescents with type I diabetes mellitus: a randomized, double-blinded placebo-controlled study.
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.


METHODS
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.
University of Colorado Denver School of Medicine, Children's Hospital Colorado, Division of Pediatric Endocrinology, Denver, CO, USA.
Kristen J
KJ
Nadeau
Kelsey
K
Chow
Suhyla
S
Alam
Kara
K
Lindquist
Sarah
S
Campbell
Kim
K
McFann
Georgeanna
G
Klingensmith
Phillipe
P
Walravens
D000293:Adolescent; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000008:administration & dosage*
D007004:Hypoglycemic Agents; D008687:Metformin
adolescents; insulin resistance; metformin; type 1 diabetes mellitus