More than one-third of adults in the USA have obesity, which causes, exacerbates or adversely impacts numerous medical comorbidities, including diabetes mellitus and cardiovascular disease. Despite intensive lifestyle modifications, the disease severity warrants further aggressive intervention, including pharmacotherapy, medical devices and bariatric surgery. Noninvasive anti-obesity drugs have thus now resurfaced as targeted adjunctive therapeutic approaches to intensive lifestyle intervention, bridging the gap between lifestyle and bariatric surgery. In this Review, we discuss FDA-approved anti-obesity drugs in terms of safety and efficacy. As most of these drugs have a mean percentage weight loss reported in clinical trials but individual variations in response rates, a future direction of obesity pharmacotherapy research might include the potential for personalized medicine to target early responders to these anti-obesity drugs.

Though there are approved anti-obesity drugs available in the USA, newer drugs are now in the pipeline for development given the urgent need. This review focuses on anti-obesity drugs in the pipeline including centrally acting agents (setmelanotide, neuropeptide Y antagonist [velneperit], zonisamide-bupropion [Empatic], cannabinoid type-1 receptor blockers), gut hormones and incretin targets (new glucagon-like-peptide-1 [GLP-1] analogues [semaglutide and oral equivalents], amylin mimetics [davalintide, dual amylin and calcitonin receptor agonists], dual action GLP-1/glucagon receptor agonists [oxyntomodulin], triple agonists [tri-agonist 1706], peptide YY, leptin analogues [combination pramlintide-metreleptin]), and other novel targets (methionine aminopeptidase 2 inhibitor [beloranib], lipase inhibitor [cetilistat], triple monoamine reuptake inhibitor [tesofensine], fibroblast growth factor 21), including anti-obesity vaccines (ghrelin, somatostatin, adenovirus36). With these new drugs in development, anti-obesity therapeutics have potential to vastly expand allowing better treatment options and personalized approach to obesity care.

A growing number of youth suffer from obesity and in particular severe obesity for which intensive lifestyle intervention does not adequately reduce excess adiposity. A treatment gap exists wherein effective treatment options for an adolescent with severe obesity include intensive lifestyle modification or metabolic and bariatric surgery while the application of obesity pharmacotherapy remains largely underutilized. These youth often present with numerous obesity‐related comorbid diseases, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, obstructive sleep apnea, nonalcoholic fatty liver disease, musculoskeletal problems, and psychosocial issues such as depression, anxiety, and social stigmatization. Current pediatric obesity treatment algorithms for pediatric primary care providers focus primarily on intensive lifestyle intervention with escalation of treatment intensity through four stages of intervention. Although a recent surge in the number of Food and Drug Administration‐approved medications for obesity treatment has emerged in adults, pharmacotherapy options for youth remain limited. Recognizing treatment and knowledge gaps related to pharmacological agents and the urgent need for more effective treatment strategies in this population, discussed here are the efficacy, safety, and clinical application of obesity pharmacotherapy in youth with obesity based on current literature. Legal ramifications, informed consent regulations, and appropriate off‐label use of these medications in pediatrics are included, focusing on prescribing practices and prescriber limits.

A medically supervised weight management program complementary to surgery is beneficial for the treatment of weight regain and may prove important in assisting the surgical patient achieve long-term weight loss success.

In 2020, impediments to pediatric obesity (PO) treatment remain pervasive, even though these barriers are clearly documented in medical literature. Providers must invest considerable resources to overcome these barriers to care. Notable barriers include gaps in medical education, misperceptions of the disease, weight bias and stigma, exclusion of coverage in health plans, and thus an unsustainable financial framework. Hence, this review offers an updated social‐ecological framework of accessibility to care, wherein each barrier to care or variable is interdependent on the other and each is critical to creating forward momentum. The sum of all these variables is instrumental to overall smooth function, configured as a wheel. To treat PO effectively, all variables must be adequately addressed by stakeholders throughout the health care system in order to holistically comprehend and appreciate undertakings to advance the burgeoning field of PO medicine.

Though residents recognize obesity and its clinical implications, it is underreported in the assessment of inpatients. This low level of documenting obesity and its impact on clinical care planning underscores a missed opportunity to establish appropriate referrals and initiate treatment at a clinically opportune time.

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