The treatment of childhood obesity represents a greater challenge for pediatricians. To date, it is multidisciplinary, including behavioral, dietary, pharmacological, and surgical options. Given the limited efficacy of available treatments, scientific research on finding new solutions is very active. Several drugs comprising Metformin, Glucagon-like peptide- 1 receptor agonists, Naltrexone-bupropion, Phentermine-Topiramate, and Lorcaserin have been studied as pediatric antiobesity agents. Findings from clinical trials showed a modest but significant effect of these drugs on weight loss, but long-term studies are needed to better define their exact role. Bariatric surgery is also promising for extremely obese adolescents. Moreover, a novel approach to treat obesity might be represented by compounds inducing browning of white adipose tissue, a complex process involved in body energy homeostasis, but at present evidence in humans is lacking. We aimed to review the current knowledge regarding the available new options for pediatric obesity treatment.

The prevalence of obesity has increased over the past three decades in the United States and worldwide. This article reviews landmark trials for lifestyle modifications as well as clinical evidence and implications for locaserin, phentermine with topiramate, buproprion with naltrexone, and liraglutide in patients with type 2 diabetes and obesity. Areas covered: A MEDLINE search, from 1970 to May 2017, was conducted using key search terms - lifestyle modifications, antiobesity medication, obesity and diabetes. Published clinical trials, in the English language, with the adult patient population of type 2 diabetes or prediabetes, were reviewed and critiqued. Expert commentary: Lifestyle modifications have shown to prevent the progression to type 2 diabetes mellitus. Pharmacologically, each medication has proven effect on both type 2 diabetes mellitus and obesity, specifically reducing weight from baseline by 4.7 kg, 10.2 kg, 5.0 kg, and 6.4 kg with lorcaserin, phentermine with topiramate, bupropion with naltrexone, and liraglutide, respectively. The most efficacious medication is phentermine with topiramate, but liraglutide has long-term evidence, up to 3 years, particularly in patient with prediabetes. A risk-benefit analysis should be completed to determine which specific medication should be initiated for a patient with type 2 diabetes and obesity.

For many years, obesity was believed to be a condition of overeating that could be resolved through counseling and short-term drug treatment. Obesity was not recognized as a chronic disease until 1985 by the scientific community, and 2013 by the medical community. Pharmacotherapy for obesity has advanced remarkably since the first class of drugs, amphetamines, were approved for short-term use. Most amphetamines were removed from the obesity market due to adverse events and potential for addiction, and it became apparent that obesity pharmacotherapies were needed that could safely be administered over the long term. This review of central nervous system (CNS) acting anti-obesity drugs evaluates current therapies such as phentermine/topiramate, which act through multiple neurotransmitter pathways to reduce appetite. In the synergistic mechanism of bupropion/naltrexone, naltrexone blocks the feed-back inhibitory circuit of bupropion to give greater weight loss. Lorcaserin, a selective agonist of a serotonin receptor that regulates food intake, and the glucagon-like-peptide-1 (GLP-1) receptor agonist liraglutide are reviewed. Future drugs include tesofensine, a potent triple reuptake inhibitor in Phase III trials for obesity, and semaglutide, an oral GLP-1 analog approved for diabetes and currently in trials for obesity. Another potential new pharmacotherapy, setmelanotide, is a melanocortin-4 receptor agonist, which is still in an early stage of development. As our understanding of the communication between the CNS, gut, adipose tissue, and other organs evolves, it is anticipated that obesity drug development will move toward new centrally acting combinations and then to drugs acting on peripheral target tissues.

Objective: The goal of this study was to obtain preliminary data on the usefulness of the combination of phentermine and topiramate extended release (phentermine-topiramate) in binge-eating disorder (BED) associated with obesity or overweight. Design: Ten participants with BED and obesity or overweightness with at least one weight-related complication received phentermine-topiramate in an open-label, prospective, 12-week trial. The primary outcome measure was change in weight. The study was registered under the identifier NCT02659475 at ClinicalTrials.gov. Results: Seven participants completed the study. Phentermine-topiramate treatment was associated with significant reductions in weight, body mass index, binge-eating episode frequency, and measures of global clinical severity, eating disorder psychopathology, and obsessive-compulsive symptoms. Mean daily dose of phentermine-topiramate at endpoint was 6.8 to 41.4mg per day. The most common adverse event (AE) was dysgeusia. There were no serious AEs, and no participants displayed symptoms of medication misuse or withdrawal. Conclusion: Phentermine-topiramate could be helpful for weight loss and reduction of binge-eating symptoms in patients with obesity or overweight in addition to BED. Controlled studies are warranted.

The objective of this review is to examine advances in the development of combination therapies for the treatment of obesity beyond diet or lifestyle interventions. Experimental combination pharmacotherapies include combinations of pramlintide and phentermine as well as amylin and bupropion-naltrexone. Incretin and pancreatic hormones generally inhibit upper gastrointestinal motor functions, and combinations showing efficacy in obesity are coadministration of glucagon-like peptide-1 (GLP-1) with glucagon, a unimolecular dual incretin of PEGylated GLP-1/GIP coagonist, the combination of GLP-1 and PYY3-36, and, in proof of concept studies, combined infusions of GLP-1, peptide YY, and oxyntomodulin. Among bariatric procedures, repeat intragastric balloon (IGB) treatments are more efficacious than IGB plus diet, and endoscopic intervention can enhance the effects of Roux-en-Y gastric bypass when weight regain occurs. A first trial has provided promising results with combination of IGB plus the GLP-1 analog, liraglutide, compared to the balloon alone. Thus, combination therapies for the treatment of obesity hold promise for introduction into clinical practice.

Various publications have noted increases in dopamine, specifically in the mesolimbic region of the brain, to have a direct correlation to psychotic-like symptoms. Venlafaxine, a first-line medication for depression, inhibits the reuptake of both serotonin and norepinephrine. Additionally, venlafaxine weakly inhibits the reuptake of dopamine. Phentermine/topiramate (Qsymia®), specifically the phentermine component, functions by blocking the dopamine and norepinephrine transporter, similar to amphetamine.

Obesity is one of the most serious and prevalent non-communicable diseases of the twenty-first century. It is also a patient-centered condition in which affected individuals seek treatment through a variety of commercial, medical and surgical approaches. Considering obesity as a chronic medical disease state helps to frame the concept of using a three-stepped intensification of care approach to weight management. As a foundation, all patients should be counseled on evidence-based lifestyle approaches that include diet, physical activity and behavior change therapies. At the second tier, four new pharmacological agents, lorcaserin, phentermine/topiramate, naltrexone/bupropion and liraglutide have been approved since 2012 as adjuncts to lifestyle modification. The third step, bariatric surgery, has been demonstrated to be the most effective and long-term treatment for individuals with severe obesity or moderate obesity complicated by co-morbid conditions that is not responsive to non-surgical approaches. By using a medical model, clinicians can provide more proactive and effective treatments in assisting their patients with weight loss.