**1. Introduction**

Management and follow-up of children and adolescents affected with obesity are crucial clinical challenges worldwide due to both high prevalence and the limited available therapeutic resources. Additionally, obesity management is highly influenced by a number of barriers both, from the patient's side (stigma, gaps in medical education, misperceptions of the disease or weight status, etc.) and from the healthcare system (insufficient staff, time and facilities to provide timely and patient/family-personalized assistance). These barriers strongly impair the probability of therapeutic success [1].

Despite the recent approval (June 2021) by the European Medicine Agency of liraglutide as the first drug for obesity treatment above 18 years of age, management of obesity in childhood and adolescent largely remains based on combined nutritional and exercise behavioral counseling, ideally involving a multidisciplinary intervention [2,3]. Although primary care assistance is recommended for childhood obesity management, the low rate of successful weight loss in these patients and the increasing prevalence of obesity associated comorbidities has resulted in obesity being one of the most frequent causes for consultation in specialized pediatric endocrinology or obesity clinics in our environment, thus generating increasing delays in patient attention [4]. Nevertheless, there is no consensus regarding the best environment to manage childhood obesity to achieve a high success in weight loss and its maintenance with, for example, primary care assistance allows for higher accessibility and proximity to patients [5] while tertiary care centers normally have more available resources and the possibility to develop multidisciplinary care units [6].

In contrast, there is robust consensus and evidence that the major factor limiting success in childhood obesity management programs is the high withdrawal rate observed throughout follow-up at all levels of assistance [7], reaching up to 92% after 2 years in some reports [8], with sociodemographic and anthropometric features being potential predictors of a higher risk of attrition [9,10]. Among these factors, the perception that obesity is not a disease state [9], initial weight loss wrongly assumed as "curation" [9,10] and, most importantly, lack of sustained weight loss [11], have been postulated as the main risk factors for early termination of intervention programs in children and adolescents with obesity. Consequently, the combination of some of these factors (early weight loss + high drop-out rate + lack of sustained weight loss), can result in selection bias in the analysis of the results of these programs in the long term.

An additional concern of parents upon intervention for childhood obesity is the potential effect on growth and pubertal development of their child. These patients usually exhibit some degree of advancement in skeletal maturation and overgrowth in relation to their target height [12,13] and this is directly correlated with the severity of their obesity and inversely proportional to the magnitude of their pubertal growth spurt [13] but does not impair the attainment of their predicted adult height [13–15]. Consequently, although severe caloric restriction is not usually included in childhood and adolescent obesity interventions [2,3] and evidence indicates that conventional strategies for weight control in this age range do not impair growth or puberty [15], this can be a factor underlying the reluctance of some parents to intervene.

Some points of discussion in childhood obesity management protocols include the degree of weight loss needed to achieve clinically significant improvements, the role (if any) of the time to attain weight loss and the amount of time this BMI reduction should be sustained for in order to preserve the beneficial effect of the intervention. A decrease in BMI Z-score of 0.25 or more has been suggested to be sufficient to improve cardiometabolic risk factors [16], whereas a duration over 3 years of intervention, beginning at the earliest age possible, has been associated with more successful outcomes [17]. However, there is limited knowledge regarding what should be considered an excellent degree of weight reduction under conservative treatment and what is an acceptable evolution after attaining this degree of weight loss [18].

A subgroup of patients with obesity that has raised special interest are those classified in some studies as "metabolically healthy" [19]. This concept of "metabolically healthy" in children with obesity was inherited from the concept first postulated in adults where a patient with excess fat mass, but normal blood pressure, lipid profile and glycemia was proposed to be metabolically healthy [20]. However, the evidence that insulin resistance is the first step of carbohydrate metabolism impairment in childhood obesity, often preceding the rise of blood glucose levels [12,21,22] and the data supporting the role of uric acid as

a potential marker of metabolic impairment in children [23] have lead to the question of whether these parameters should also be considered before assuming that a child with obesity is "metabolically healthy" [20–22].

Based on the above observations, we hypothesized that the time required to obtain a significant reduction in BMI affects both the attrition rate and the degree of improvement in metabolic impairment in children with obesity. Thus, the aims of this study were: (1) To analyze the duration of follow-up, the drop-out rate and its causes and the behavioral changes implemented, along with the patient's BMI Z-score, growth and metabolic evolution up to a maximum of 7 years in the regular outpatient care in an obesity clinic in a tertiary hospital, with a particular emphasis on BMI changes and attrition rate. (2) To study the features of patients achieving a large reduction in BMI ("excellent responders"), characterizing their weight loss and metabolic changes, the evolution of their BMI in the 5 years following weight reduction and exploring how the time required to attain weight loss affects the metabolic changes observed. (3). To compare the features of patients with obesity, with or without metabolic comorbidities during their first evaluation, as well as the evolution of their metabolic status according to BMI changes during follow-up, while evaluating the role of insulin resistance in the definition of a "metabolically healthy status".
