Adolescent obesity treatments: news, views, and evidence

Cominato, Louise; Franco, Ruth; Damiani, Durval

doi:10.20945/2359-3997000000393

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Archives of Endocrinology and Metabolism

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Review • Arch. Endocrinol. Metab. 65 (5) • 2021 • https://doi.org/10.20945/2359-3997000000393 copy

Adolescent obesity treatments: news, views, and evidence

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Obesity is a complex and multifactorial disease that is influenced by physiological, environmental, socioeconomic, and genetic factors. In recent decades, this serious disease has impacted a large number of adolescents as a result of lifestyle factors. A lack of exercise and the consumption of excessive calories from an inadequate diet are the main contributors to adolescent obesity. However, genetic and hormonal factors might also play a role. The short- and long-term consequences of this disease include chronic issues such as type 2 diabetes and cardiovascular disorders and an increase in early mortality rates. Although it is a serious disease, obesity in adolescents can be controlled with diet and exercise. When these lifestyle changes do not obtain the expected results, we can intensify the treatment by adding medication to the practice of diet and exercise. Additionally, for more severe cases, bariatric surgery can be an option. The purpose of this review is to clarify the current epidemiology, risks, and comorbidities and discuss news about the main treatments and the necessary improvements in this context.

Keywords
Obesity; overweight, adolescent; treatment; liraglutide

Drug	Mechanism of action
Liraglutide ( ³⁴34. Scott LJ. Liraglutide: a review of its use in the management of obesity. Drugs. 2015;75(8):899-910. )	The GLP-1 receptor is expressed in neurons of the arcuate nucleus of the hypothalamus involved in weight loss. Liraglutide is aGLP-1 receptor agonist that directly stimulates neurons that synthesize POMC/CART (increasing satiety). Indirectly inhibits neurotransmission in neurons that express NPY/AGRP (reducing hunger), GABA-dependent signaling pathways. Liraglutide binds in key areas linked to the control of energy balance, circuits linked to reward and pleasure. Decrease of speed of gastric emptying is temporary. Its action independent of the vagus nerve.
Orlistat ( ³¹31. Mead E, Atkinson G, Richter B, Metzendorf MI, Baur L, Finer N, et al. Drug interventions for the treatment of obesity in children and adolescents. Cochrane Database Syst Rev. 2016;(11):CD012436. )	Inhibitor of gastrointestinal lipases that binds to the active site of the enzyme through covalent binding. This binding prevents digestion and intestinal absorption of about one-third of the ingested triglycerides that are eliminated in the stool.
Sibutramine ( ³¹31. Mead E, Atkinson G, Richter B, Metzendorf MI, Baur L, Finer N, et al. Drug interventions for the treatment of obesity in children and adolescents. Cochrane Database Syst Rev. 2016;(11):CD012436. )	Blocking the reuptake of norepinephrine and serotonin that triggers neurotransmission modulation and increased feeling of satiety.
Metformin ( ³¹31. Mead E, Atkinson G, Richter B, Metzendorf MI, Baur L, Finer N, et al. Drug interventions for the treatment of obesity in children and adolescents. Cochrane Database Syst Rev. 2016;(11):CD012436. )	The exact mechanism of action is not fully understood. Reduces blood glucose due to the insulin-sensitizing effect in liver and muscle tissue. In the hepatocyte, induces gluconeogenesis and glycogenolysis inhibition, and glycogenesis stimulation. In peripheral insulin-dependent tissues, especially in skeletal muscle, glucose uptake increases, causing a rapid reduction in blood glucose.
Topiramate ( ⁴⁷47. Fox CK, Marlatt KL, Rudser KD, Kelly AS. Topiramate for weight reduction in adolescents with severe obesity. Clin Pediatr (Phila). 2015;54(1):19-24. )	It acts on several neurotransmitters, having inhibitory effects on glutamate receptors and some types of voltage-gated calcium and sodium channels. It modulates some potassium channels, GABA-A receptors, in addition to being a weak inhibitor of carbonic anhydrase.

Drug	Status	Dose	Efficacy	95% CI	Common adverse events
Liraglutide ( ³⁵35. Kelly AS, Auerbach P, Barrientos-Perez M, Gies I, Hale PM, Marcus C, et al. A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity. N Engl J Med. 2020;382(22):2117-28. )	Approved for the treatment of adolescent with obesity and obesity or overweight in adults with associated comorbidity.	3.0 mg/day/subcutaneous (titration ^* * titration (weekly): 0.6, 1.2, 1.8, 2.4 up to 3.0 mg )	1,39 Kg/m² BMI reduction	−1.08 to −1.70	Nausea, diarrhea, constipation, vomiting, headache, dyspepsia, fatigue, dizziness, abdominal pain, slight increase in lipase without pancreatitis.
Orlistat ( ³¹31. Mead E, Atkinson G, Richter B, Metzendorf MI, Baur L, Finer N, et al. Drug interventions for the treatment of obesity in children and adolescents. Cochrane Database Syst Rev. 2016;(11):CD012436. )	Approved for the treatment of obesity or overweight in adults with associated comorbidity.	360 mg/day	0.79 Kg/m² BMI reduction	−1.08 to −0.51	Oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, increased defecation, fecal incontinence.
Sibutramine ( ³¹31. Mead E, Atkinson G, Richter B, Metzendorf MI, Baur L, Finer N, et al. Drug interventions for the treatment of obesity in children and adolescents. Cochrane Database Syst Rev. 2016;(11):CD012436. )	Approved for the treatment of obesity or overweight in adults with associated comorbidity.	10-15 mg/day	1.70 Kg/m² BMI reduction	−2.89 to −0.51	Tachycardia, hypertension, palpitations, insomnia, anxiety, nervousness, depression, diaphoresis.
Metformin ( ³¹31. Mead E, Atkinson G, Richter B, Metzendorf MI, Baur L, Finer N, et al. Drug interventions for the treatment of obesity in children and adolescents. Cochrane Database Syst Rev. 2016;(11):CD012436. )	Approved for children over 10 years with DM2.	1,000-2,000 mg/day	1.35 Kg/m² BMI reduction	−2.00 to −0.69	Nausea, flatulence, bloating, diarrhea; usually resolves.
Topiramate ( ⁴⁷47. Fox CK, Marlatt KL, Rudser KD, Kelly AS. Topiramate for weight reduction in adolescents with severe obesity. Clin Pediatr (Phila). 2015;54(1):19-24. )	Approved for children and adult epilepsy treatment and adult migraine prophylaxis.	25-100 mg/day	Controversial data	–	Cognitive dysfunction, kidney stones, metabolic acidosis; teratogenic: adolescents must be counseled against pregnancy because of decrease in efficacy of oral contraceptives

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[1] Correspondence to: Louise Cominato, Rua Simão Álvares, 51, Pinheiros 05410-000 – São Paulo, SP, Brasil. louise.cominato@hotmail.com