Effect of Metformin on Adolescent Obesity

Objectives: Metformin is the first line treatment for type 2 diabetes mellitus (T2DM) in both adults and children and has been shown to result in weight loss. Pediatric obesity is a major risk factor for the development of T2DM as well as several other diseases. Recently, physicians have reported using Metformin off-label to treat obesity in adolescent patients. The purpose of this study is to investigate whether Metformin is effective in reducing BMI in obese adolescents. Methods: Studies were found using PubMed, MeSH, Medline, and CINAHL. The search terms used were: “obesity,” Metformin,” “adolescents,” “children,” “metformin and weight,” and “metformin and BMI. ” Several studies were excluded, including meta-analysis studies, reviews, studies written in a foreign language, and studies published before 2000. Studies were also excluded if their sample populations included ages below 6 years old or above 18 years old, if they included participants with T2DM, and studies that involved other drugs besides Metformin. The final 3 studies were chosen based on their relevance to our clinical question. Results: The first study showed a significant reduction in BMI z score of 0.8 +/-0.2 in prepubertal children, and a nonsignificant reduction of 0.4+/-0.2 in pubertal children. Study 2 showed a significant reduction in BMI-SDS from 3.44 (SD 0.57) to 3.35 (SD 0.65). In Study 3, BMI-SDS was significantly higher in the metformin group compared to the lifestyle intervention group. After 12 months of treatment, this difference disappeared. However, the change in BMISDS between the metformin group and lifestyle intervention group in Study 3 was not significant. Conclusion: Further studies need to be done to determine the role of metformin in treating obese, non-diabetic adolescents. While current studies suggest some benefit of metformin in childhood obesity, sample sizes are relatively low, and results vary between prepubertal and pubertal children. However, our research did show a decrease in standardized BMI in obese pediatric patients receiving metformin, indicating a possible role of metformin in treating adolescent obesity. Introduction Pediatric obesity, defined as a BMI equal to or greater than the 95th percentile for age and gender, has been a growing concern worldwide among both resource-rich and resourcepoor countries. Among adolescents in the United States, there was a sharp increase in obesity prevalence from 5.0% in 1976 to 20.6% in 2014, highlighting the true extent of the disease and indicating a need for early intervention. Along with upward trends in pediatric obesity, we have seen an increase in associated comorbidities. Diseases such as type 2 diabetes mellitus (T2DM) and fatty liver disease that have long been considered adult diseases are being seen more frequently in pediatric patients. Early onset diabetes markedly increases the risk for developing complications such as retinopathy, neuropathy, nephropathy, and atherosclerotic cardiovascular disease. Adolescent Mackenzie McNamee Victoriya Eggen obesity also poses an increased risk for hypertension, dyslipidemia, cholelithiasis, obstructive sleep apnea, musculoskeletal problems, early onset polycystic ovarian syndrome (PCOS), and premature death in adulthood. Important considerations also include the psychosocial factors of self-esteem, peer relationships, body image, and depression among obese adolescents. Metformin is the first line treatment for T2DM in adults and adolescents, as it effectively decreases hepatic glucose production and increases insulin sensitivity in peripheral tissues. It is relatively well-tolerated, with the most common side effects related to GI disturbances. Along with its benefits of controlling T2DM, metformin has also been shown to cause weight loss. Given its favorable effect on weight, our research focuses on the use of metformin in treating obesity in adolescents. While metformin is approved for treating T2DM in patients 10 years and older, there is limited research on its use for treating childhood obesity. This literature review investigates whether metformin is effective in lowering BMI in obese, nondiabetic adolescents. Case J.W. is a 10yo white male presenting to the pediatrician with his parents for concerns regarding his weight. He has a height of 56in and weighs 102 pounds, placing him in the 95th percentile for BMI (figure 1). Both of his parents are overweight and have T2DM. In addition, his grandfather just passed away due to complications from cardiovascular and end stage renal disease as a result of diabetes. J.W. ’s parents are worried about their son’s health, and previous attempts at diet and exercise modifications have had limited success. His parents also report that J.W. is being bullied at school because of his weight and are concerned for his psychological health. J.W. ’s parents are inquiring if there are any medications that could help him lose weight. J.W. himself also seems motivated to lose weight. Methods A database search on PubMed, MeSH, Medline, and CINAHL was performed using the search terms “obesity,” “metformin,” “adolescents,” “children”, “metformin and weight,” and “metformin and BMI. ” Filters were implemented to include articles that were published in 2010 or later and were full-text. Initially, articles were excluded if they were meta-analysis studies, reviews, or written in a foreign language. Other exclusion criteria included: Research published before the year 2000, or Figure 1: J.W. ’s height and weight plotted on a pediatric growth curve for boys 2-20yo Mackenzie McNamee Victoriya Eggen studies involving participants with T2DM, subjects younger than 6 or older than 18, girls with obesity and PCOS, and studies investigating antihyperglycemic drugs other than metformin. Eighty-eight studies on metformin for childhood obesity were identified from the abovementioned databases using the exclusion criteria. In some cases, further references were identified from reference lists provided by the studies. The searches of electronic databases were supplemented with manual screening of the bibliographies of retrieved publications. The bibliographies of recent systematic reviews and other review articles for potentially relevant citations were also screened. Additional records identified through these other sources summed up to 682 results. All articles identified were subject to the study selection criteria listed above. Upon manual analysis of the articles found, additional exclusions were made by eliminating study protocols, systematic reviews, studies that measured outcomes other than obesity, studies comparing metformin to another drug instead of placebo, or studies with lengths of less than 6 months. Finally, three articles were chosen, two RCT and one retrospective cohort study, as these were studies that best addressed our clinical question.