Affiliation:
1. Discipline of Paediatrics, Robinson Research Institute, University of Adelaide, Australia
2. Endocrinology and Diabetes Department, Women’s and Children’s Hospital, Australia
3. School of Public Health, Faculty of Health and Medical Sciences, University of Adelaide, Australia
4. Pharmacy, Women’s and Children’s Hospital, Australia
5. Medical Imaging, Women’s and Children’s Hospital, Australia
6. Flinders Medical Centre, Bedford Park, Australia
Abstract
Abstract
Context
Children with type 1 diabetes have vascular dysfunction preceding atherosclerosis. Early interventions are needed to reduce cardiovascular disease.
Objective
To evaluate the effect of metformin on vascular function in children with type 1 diabetes.
Design
Twelve-month double-blind, randomized, placebo-controlled trial.
Setting
Tertiary pediatric diabetes clinic.
Participants
Ninety children (8 to 18 years of age), >50th percentile body mass index (BMI), with type 1 diabetes.
Intervention
Metformin (up to 1 g twice a day) or placebo.
Main Outcome Measure
Vascular function measured by brachial artery ultrasound [flow-mediated dilatation/glyceryl trinitrate–mediated dilatation (GTN)].
Results
Ninety participants were enrolled [41 boys, 13.6 (2.5) years of age, 45 per group], 10 discontinued intervention, and 1 was lost to follow-up. On metformin, GTN improved, independent of glycosylated hemoglobin (HbA1c), by 3.3 percentage units [95% confidence interval (CI) 0.3, 6.3, P = 0.03] and insulin dose reduced by 0.2 U/kg/d (95% CI 0.1, 0.3, P = 0.001) during 12 months, with effects from 3 months. Metformin had a beneficial effect on HbA1c at 3 months (P = 0.001) and difference in adjusted HbA1c between groups during 12 months was 1.0%; 95% CI 0.4, 1.5 (10.9 mmol/mol; 95% CI 4.4, 16.4), P = 0.001. There were no effects on carotid/aortic intima media thickness, BMI, lipids, blood pressure, or other cardiovascular risk factors. Median (95% CI) adherence, evaluated by electronic monitoring, was 75.5% (65.7, 81.5), without group differences. More gastrointestinal side effects were reported on metformin (incidence rate ratio 1.65, 95% CI 1.08, 2.52, P = 0.02), with no difference in hypoglycemia or diabetic ketoacidosis.
Conclusions
Metformin improved vascular smooth muscle function and HbA1c, and lowered insulin dose in type 1 diabetes children. These benefits and good safety profile warrant further consideration of its use.
Funder
Diabetes Australia Research Trust
Subject
Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism
Cited by
54 articles.
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