Metformin Treatment of Pediatric Obesity

Childhood obesity has steadily become a contemporary epidemic with serious public health implications.1 Approximately 70% of children will remain obese in adulthood.2 Obesity is risk factor for development atherosclerosis and type 2 diabetes mellitus (T2DM),3 its prevention management represents priority pediatric primary care providers. This underscores the need evidence-based interventions adolescents obesity, including pharmacotherapy.4Metformin US Food Drug Administration (FDA) approved use 10 years age older T2DM been used off label to achieve weight loss children. In current issue Pediatrics, Masarwa et al5 present systematic review safety efficacy metformin from randomized controlled trials (RCTs) adolescents. The authors demonstrated that therapy resulted modest benefits reduction BMI those obesity. Among 14 RCTs which was reported, modestly efficacious at decreasing (range mean changes: −2.70 1.30) compared placebo (−1.12 1.90). As pointed out by authors, results across studies were heterogeneous, 11 suggesting it decreased BMI, whereas 3 revealed an increase BMI. 7 z score consistently decrease −0.37 −0.03) when (−0.22 0.15), largest observed nonalcoholic fatty liver disease. insulin resistance examined, but favorable effects on resistance. Metformin therapy, however, associated doubling rate gastrointestinal adverse events placebo. brings up whether reasonable adjunct behavioral lifestyle modifications treatment childhood obesity.Options patients are significantly limited.6,7 Lifestyle modification incorporates nutritional, physical activity, behavior modification, mainstay management, both adults. Although successful underpinned achieving durable this approach challenging. biology gain regulation appetite, satiety, energy through basal metabolism exercise tightly central peripheral mechanisms undermine ability lose weight. Therefore, additional therapies, such as pharmacologic treatments, attractive options before proceeding bariatric surgery.Several antiobesity drugs have FDA among adult numerous clinical conducted support their use.8 children, only FDA-approved pharmacotherapies orlistat liragutide persons 12 phenteremine 16 older. Orlistat may cause intolerable side possible fat-soluble vitamin deficiency. Phentermine short-term heart blood pressure irritability insomnia. Long-term not available. Glucagon-like peptide-1 receptor agonist, liraglutide, second-line Liragutide adults since 2014 shown RCT.7 About 43% treated 18% had 5% 26% 8% respectively, 10% seen. It recently December 2020. dose differs T2DM. >12 body >60 kg sex corresponding 30 kg/m2 or greater adults, reduced calorie diet increased activity. Its limited daily subcutaneous injections high frequency cost.The combination topiramate phentermine available management. Small alone suggest meaningful occur, cognitive dysfunction.9 Other agents include lorcaserin, 5-hydroxytryptamine 2C naltrexone bupropion. Setmelanotide, melanocortin-4-receptor agonist >6 monogenic due three rare genetic conditions: pro-opiomelanocortin (POMC) deficiency, proprotein subtilisin/kexin 1 (PCSK1) leptin (LEPR) There several other obesity.10Understandably, caring moderate severe looking adjuncts promote loss. recent study, Borzutzky al4 indicated pharmacotherapy prescribing appears be increasing providers treating despite lack approval youth. According most prescribed drug 2014, 2017.Metformin reduces hepatic glucose production, decreases intestinal absorption, increases sensitivity reduce appetite raising glucagon-like levels. precise mechanism action completely understood. profile, can minimized slowly dosage. sustainability unknown, recommend reserved and, perhaps, polycystic ovary syndrome youth.Ideally, should entered into trial rather than placed off-label medication. low-cost option provide benefit minimal effects. If pursued achieved loss, try agent adjunctive therapy. Many gaps knowledge effective therapies more prevalent families neighborhoods low socioeconomic status.11 We clearly novel cost-effective approaches help burden disease our youth general.