Clinical Use of Metformin in Non-Diabetic, Obese, At-Risk Adolescents: A Systematic Review

Background: Type 2 diabetes (T2D) is a disease effecting people of every age, ethnicity, and gender and rates of the disease do not appear to be declining in the near future. The road to T2D is characterized by the combination of peripheral insulin resistance and inadequate insulin secretion by pancreatic beta cells. Although the factors that contribute to the development of T2D are complex and not fully elucidated, the triad of severe obesity, hyperinsulinemia, and a family history of T2D is known to place a child at an increased risk for subsequent development of the disease. The purpose of this study is to explore the preventative potential of metformin in obese, non-diabetic adolescents at-risk for the development of T2D. Methods: An exhaustive search of available medical literature was conducted using Medline-OVID, CINAHL, and Google Scholar using the key words: adolescents, metformin, diabetes – prevention and control, obesity, and diabetic risk factors. Articles with primary data evaluating the use of metformin in obese, non-diabetic adolescents were included. These relevant articles were assessed for quality using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results: Three studies met the inclusion criteria for this systematic review of literature. A double-blind, placebo-controlled study of the effects of metformin on body mass index and glucose tolerance in 29 obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes demonstrated a significant decline in BMI and decreased insulin and glucose concentrations. Another double-blind, placebo-controlled study of metformin in non-diabetic, hyperinsulinemic, obese adolescents maintained on a low-calorie diet demonstrated statistically significant weight loss in the metformin group as well as improved insulin concentrations. Lastly, a randomized double-blind placebo-controlled trial evaluating metformin in addition to personal goal setting with weight loss and clinical status in 85 obese adolescents with insulin resistance demonstrated significant decrease in BMI in females with metformin adherence and lifestyle changes. Conclusion: Metformin has been demonstrated to aid with weight loss and insulin sensitivity in select obese, non-diabetic adolescents with risk factors for diabetes. The overall combined quality of the studies reviewed is low based on the GRADE criteria. A recommendation for the use of metformin in obese, non-diabetic, at-risk adolescents who are motivated to create lifestyle changes can be given at this time for short term weight loss goals and increasing insulin sensitivity. Degree Type Capstone Project Degree Name Master of Science in Physician Assistant Studies First Advisor Sage-Davis Risen, PA-C This capstone project is available at CommonKnowledge: http://commons.pacificu.edu/pa/426 Second Advisor Annjanette Sommers, PA-C