Efficacy of Liraglutide on childhood and adolescent obesity
Introduce
The frequency of obesity in children and adolescents has skyrocketed in recent decades [ 1 ], affecting approximately 107.7 million children and adolescents worldwide [ 2 ]. Obesity is a complex, recurrent chronic condition [ 3 ], defined by abnormal body fat accumulation [ 4 , 5 ]. This complex disturbance of energy balance involves fat cells, the digestive system and the brain, by regulating food intake and energy expenditure [6 ] . Obesity is a risk factor that contributes significantly to the global burden of serious diseases [7], of which 1.1 billion adults and 10% of children are obese or overweight. This leads to reduced life expectancy [ 9 ,10 ].
Childhood obesity is associated with a number of health problems, including arterial hypertension (AHT), cardiovascular disease, type 2 diabetes, atherosclerosis, dyslipidemia, etc. – 13 ]. In addition, childhood obesity can also affect quality of life, leading to negative psychological problems such as low self-esteem, depression, and impaired school performance [14 ] . Currently, treatments for childhood obesity are multimodal [4], with an emphasis on dietary promotion and exercise-related lifestyle changes [15 , 16 ] .
The current application of drugs to control childhood obesity is limited [ 6 ]. The Food and Drug Administration (FDA) has approved three drugs to treat childhood obesity: orlistat for patients under 12 years of age, phentermine for patients over 16 years of age, and liraglutide for adolescents 12 to 17 years of age. age [ 17,18]. Liraglutide is a GLP-1 (glucagon-like peptide 1) receptor agonist that improves glucose regulation, increases glucose-dependent insulin secretion, in pancreatic β cells and decreases glucagon secretion in α cells. ). Liraglutide “mimics” a hormone in the gut, sending a “full” signal to the brain, helping to increase satiety and reduce hunger. The drug helps to lose body weight mainly through fat mass reduction with a greater reduction in visceral fat than subcutaneous fat. The highest recommended dose of liraglutide for the anti-obesity indication is 3.0 mg daily [ 19 ].
Most existing pharmacological therapies for obesity have failed to demonstrate adequate efficacy due to undesirable side effects, leading to discontinuation of some drugs because of concerns about their safety. patients [20]. Therefore, determining the efficacy of liraglutide in the treatment of obesity in children and adolescents was the aim of this study.
Research Methods
The study was conducted to evaluate the effectiveness of liraglutide in the treatment of obesity in children and adolescents. A systematic search was performed in the PubMed, Scopus, Web of Science and Embase databases. The search was completed on October 20, 2022, and two investigators conducted an independent review of the search results.
Selection criteria
Selection studies met the following conditions: (1) Randomized Controlled Trial (RCT); (2) Pediatric patients (5–≤18 years) diagnosed with obesity as defined by the study authors, (3) Liraglutide (3.0 mg dose) as the intervention/trial group and (4) standard and placebo treatment controls.
Exclusion criteria
The following studies will be excluded: Systematic reviews, meta-analyses, narrative reviews, editorials, abstracts, reports, and case series.
Features of the studies
Using the search method, a total of 185 articles were found. After removing duplicates, the reviewers examined 123 articles. After title and abstract filtering, 27 articles were selected for full-text review and three were deemed acceptable for inclusion in this systematic review and meta-analysis [ 8 , 21 , 22 ] . The number of participants varied according to the respective author’s criteria, in this systematic review a total of 296 participants [8, 21 , 22]]. All studies analyzed in the present investigation were Phase 3 randomized clinical trials with a maximum dose of Liraglutide of 3.0 mg. The three studies reviewed were all mutually supportive as the findings were similar. It can be concluded in three studies that treatment with Liraglutide in pediatric patients caused positive changes in their health as a result of drug use, such as reductions in body weight, BMI, and stages of disease. adverse effects, yielding results that support tolerability and safety [ 8,21,22 ].
Summary of results and discussion
A comprehensive analysis of the three studies above showed no clinically significant difference between liraglutide and body weight (kg; MD -2.62; 95% CI -6.35 to 1.12; p) . = 0.17) and body mass index (kg/m 2 ; MD −0.80; 95%CI −2.33 to 0.73, p = 0.31). There was no evidence that liraglutide increased episodes of hypoglycemia (RR 1.08; 95% CI 0.37 to 3.15; p = 0.79) or adverse effects. Although this is not the first systematic review and meta-analysis to focus on the effects of liraglutide, it is one of the first studies to be performed in children (5–18 years of age) without comorbidities, such as diabetes mellitus.
Currently, there is little use of pharmacological therapies for childhood obesity, with inadequate evidence for each treatment option [23 ] . The drugs are glucagon-like peptide-1 receptor agonists (GLP-1RA) designed to reduce body weight in patients with type 2 diabetes mellitus (T2DM), and Liraglutide was the first GLP-1RA to be approved. approved for the treatment of obesity in people with and without type 2 diabetes mellitus (T2DM) [24].
Chadda KR et al. reported that GLP-1 agonist therapy resulted in a greater reduction in body weight in obese children than in children with T2DM [25]. Thus, increased GLP-1 secretion leads to increased insulin secretion, promotes hepatic adipogenesis, and promotes adipogenesis, which may explain the correlation of fasting GLP-1 with percentage of muscle fat. body, triglycerides and alanine aminotransferase [26 ] .
Research by T. Danne et al. presented evidence that the safety and tolerability profile of liraglutide in adolescents with obesity was comparable to that in adults, with no other safety/tolerability concerns expected. Participants received only Liraglutide 3.0 mg for 1 to 2 weeks, so the long-term efficacy and safety of Liraglutide could not be established in this group of adolescents [22] due to the small sample size and duration of treatment . short value.
Research by Mastrandrea LD et al. presented evidence of short-term therapy with liraglutide in obese children, showing a safety profile and tolerability comparable to studies in obese adults and adolescents, with no additional association Any concerns about safety. However, long-term safety could not be assessed in the approximately 7-week trial in this study [8].
Research has demonstrated that the drug can help reduce BMI and weight when combined with a healthy diet and regular exercise. Lifestyle changes that may have favorable outcomes will be evaluated in the future for adjuvant therapy. Research by Kelly AS et al. provides evidence that lifestyle improvements are associated with weight control in adolescents. The use of Liraglutide for 56 weeks showed no significant effects on cardiovascular metabolic risk variables such as blood pressure, serum cholesterol, and triglycerides [21 ] . However, energy intake and physical activity were important factors affecting body weight and no data on these variables were reported at the start of the study and at the end of the study. [21].
Conclude
Effective therapy for adolescent obesity requires a focus on assessing quality of life and avoiding obesity-related comorbidities [49] in addition to weight loss . The optimal therapy for adolescent obesity should be a tailored and highly customized medication that takes into account age, coexisting disorders, drug tolerance, medical problems at local and economic [50 , 51 ] .
Limit
This systematic review has many limitations. Studies have not demonstrated beneficial effects. Many studies have small sample sizes, short follow-up periods, or need a control group, making it difficult to evaluate study findings. Third, none of the trials were designed primarily to evaluate a limited-time BMI reduction at maximum dosage. In addition, none of these clinical trials collected lifestyle-related data.
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