New AOMs for Paediatric Obesity

The emergence of new anti-obesity medications (AOMs) has changed the landscape of pediatric weight management, improving the outlook for youth with obesity. In this article, we will review the current evidence and guidelines for the use of AOMs in children and adolescents, as well as the challenges and opportunities for their integration into clinical practice.

Obesity is a chronic and complex disease that affects millions of children and adolescents worldwide. It is associated with an increased risk of various comorbidities, such as type 2 diabetes, hypertension, dyslipidemia, non-alcoholic fatty liver disease, obstructive sleep apnea, and psychosocial problems. Moreover, obesity in childhood often persists into adulthood, leading to further complications and reduced quality of life.

The cornerstone of paediatric weight management is lifestyle modification, which includes dietary changes, physical activity, behavioural therapy, and family involvement. However, lifestyle interventions alone are often insufficient to achieve and maintain clinically significant weight loss in youth with obesity, especially those with severe obesity or comorbidities. Therefore, additional treatment options are needed to complement and enhance the effects of lifestyle interventions.

AOMs are pharmacological agents that target different pathways involved in energy balance and appetite regulation. They can help reduce body weight by decreasing energy intake, increasing energy expenditure, or both. AOMs are not intended to replace lifestyle interventions, but rather to augment them by facilitating adherence and improving outcomes.

Several AOMs have been approved for adults with obesity, but only a few have been studied and approved for children and adolescents. The most commonly used AOMs in paediatric populations are orlistat, metformin, liraglutide, and phentermine-topiramate. These agents have different mechanisms of action, efficacy, safety profiles, and indications. Therefore, the choice of AOM should be individualized based on the patient’s age, weight status, comorbidities, preferences, and potential side effects.

Orlistat is a lipase inhibitor that reduces the absorption of dietary fat by about 30%. It is approved for children aged 12 years and older with a body mass index (BMI) of 30 kg/m2 or higher, or 28 kg/m2 or higher with comorbidities. It can induce a modest weight loss of about 3% compared to placebo over 12 months. The main adverse effects are gastrointestinal symptoms, such as oily spotting, flatulence, fecal urgency, and abdominal pain. These symptoms can be minimized by reducing fat intake and taking multivitamins.

Metformin is a biguanide that lowers blood glucose levels by decreasing hepatic gluconeogenesis and increasing peripheral glucose uptake. It is not approved for weight management in children or adults, but it is widely used off-label for youth with obesity and insulin resistance or type 2 diabetes. It can induce a modest weight loss of about 2% compared to placebo over 6 months. The main adverse effects are gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and abdominal pain. These symptoms can be minimized by starting with a low dose and titrating up gradually.

Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that stimulates insulin secretion and inhibits glucagon secretion in a glucose-dependent manner. It also reduces appetite and food intake by acting on the hypothalamus and the brainstem. It is approved for adults with a BMI of 30 kg/m2 or higher, or 27 kg/m2 or higher with comorbidities. It is also approved for children aged 12 years and older with a BMI at or above the 95th percentile. It can induce a significant weight loss of about 10% compared to placebo over 12 months. The main adverse effects are gastrointestinal symptoms,
such as nausea, vomiting, diarrhea, constipation, and abdominal pain. These symptoms tend to decrease over time and can be minimized by starting with a low dose and titrating up slowly.

Phentermine-topiramate is a combination of two drugs that act on the central nervous system to suppress appetite and enhance satiety. Phentermine is a sympathomimetic amine that stimulates the release of norepinephrine in the hypothalamus. Topiramate is an anticonvulsant that modulates several neurotransmitter systems involved in appetite regulation. It is approved for adults with a BMI of 30 kg/m2 or higher,
or 27 kg/m2 or higher with comorbidities. It is not approved for children or adolescents,
but it has been studied in youth aged 12 to 17 years with severe obesity (BMI at or above
the 97th percentile). It can induce a significant weight loss of about 9% compared to placebo over 12 months. The main adverse effects are central nervous system symptoms, such as paresthesia, dizziness, insomnia, dry mouth, and cognitive impairment. These symptoms can be minimized by starting with a low dose and titrating up gradually.

The use of AOMs in children and adolescents requires careful consideration of the benefits and risks, as well as close monitoring of the patient’s growth, development, and metabolic parameters. AOMs should be prescribed by experienced clinicians who are familiar with the indications, contraindications, dosages, and potential interactions of these agents. AOMs should be initiated only after a comprehensive assessment of the patient’s medical history, physical examination, laboratory tests, and psychological evaluation. AOMs should be discontinued if the patient does not achieve a clinically meaningful weight loss (at least 4% of baseline weight) after 12 weeks of treatment, or if the patient develops intolerable or serious side effects.

AOMs are not a magic bullet for paediatric obesity, but they can be a valuable tool to help some youth with obesity achieve better health and quality of life. AOMs should be used as part of a multidisciplinary and family-based approach that includes lifestyle modification, behavioural therapy, and psychosocial support. More research is needed to evaluate the long-term efficacy and safety of AOMs in children and adolescents, as well as to develop new and more effective agents for this population.

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