ABSTRACT Pharmacological treatment of obesity is passing through many changes in the last decades; different agents have been approved, and newer options are leaning towards higher efficacy and a more favourable safety profile; however, medications approved for a longer time are still available and useful for many patients. This document is an 2024 Update Position Statement of Specialists from the Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso) and the Brazilian Society of Endocrinology and Metabolism (SBEM), with the aim of reviewing all the approved medications for the management of obesity in Brazil (sibutramine, orlistat, liraglutide, semaglutide and bupropion/naltrexone fixed dose), with the addition of tirzepatide, that is approved in other countries and likely approved soon in Brazil. The review is focused on efficacy, safety profile and the impact of drugs (based on existing studies) on different comorbidities. decades however patients 202 Abeso (Abeso SBEM, SBEM , (SBEM) sibutramine, sibutramine (sibutramine orlistat liraglutide bupropionnaltrexone bupropion naltrexone dose, dose dose) tirzepatide based studies comorbidities 20 (SBEM 2

ABSTRACT Obesity is a chronic disease associated with impaired physical and mental health. A widespread view in the treatment of obesity is that the goal is to normalize the individual's body mass index (BMI). However, a modest weight loss (usually above 5%) is already associated with clinical improvement, while weight losses of 10%-15% bring even further benefits, independent from the final BMI. The percentage of weight reduction is accepted as a treatment goal since a greater decrease in weight is frequently difficult to achieve due to metabolic adaptation along with environmental and lifestyle factors. In this document, the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO) propose a new obesity classification based on the maximum weight attained in life (MWAL). In this classification, individuals losing a specific proportion of weight are classified as having “reduced” or “controlled” obesity. This simple classification – which is not intended to replace others but to serve as an adjuvant tool – could help disseminate the concept of clinical benefits derived from modest weight loss, allowing individuals with obesity and their health care professionals to focus on strategies for weight maintenance instead of further weight reduction. In future studies, this proposed classification can also be an important tool to evaluate possible differences in therapeutic outcomes between individuals with similar BMIs but different weight trajectories.

ABSTRACT Obesity is a chronic disease associated with impaired physical and mental health. A widespread view in the treatment of obesity is that the goal is to normalize the individual's body mass index (BMI). However, a modest weight loss (usually above 5%) is already associated with clinical improvement, while weight losses of 10%-15% bring even further benefits, independent from the final BMI. The percentage of weight reduction is accepted as a treatment goal since a greater decrease in weight is frequently difficult to achieve due to metabolic adaptation along with environmental and lifestyle factors. In this document, the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO) propose a new obesity classification based on the maximum weight attained in life (MWAL). In this classification, individuals losing a specific proportion of weight are classified as having “reduced” or “controlled” obesity. This simple classification – which is not intended to replace others but to serve as an adjuvant tool – could help disseminate the concept of clinical benefits derived from modest weight loss, allowing individuals with obesity and their health care professionals to focus on strategies for weight maintenance instead of further weight reduction. In future studies, this proposed classification can also be an important tool to evaluate possible differences in therapeutic outcomes between individuals with similar BMIs but different weight trajectories.

INTRODUÇÃO: Estudos prévios sugeriram que os níveis plasmáticos da retinol binding protein (RBP4), uma proteína do tecido adiposo, estão associados com a resistência à insulina (RI). A lipodistrofia congênita generalizada (LCG) é uma doença rara caracterizada por ausência de tecido adiposo e RI. O objetivo é determinar os níveis de RBP4 em pacientes com LCG. SUJEITOS E MÉTODOS: Seis (6) pacientes com LCG e um grupo controle saudável foram selecionados para participar no estudo. As variáveis antropométricas e bioquímicas foram comparadas quando comparados os grupos. RESULTADOS: Nenhuma diferença foi observada entre os níveis de RBP4 log entre os grupos (LCG 42,5 [12,5 - 127] vs. controle 57,4 [15,9 - 165]; p = 0,78). Por outro lado, os níveis de leptina foram menores em pacientes com LCG (LCG 0,65 [0,2 - 0,7] vs. controle 10.9 [0,9 - 38,6]; p = 0,015). Nenhuma correlação foi encontrada entre RBP4 e cintura (r = 0,18, p = 0,57) ou IMC (r = 0,24, p = 0,45). CONCLUSÃO: RBP4 não está diminuída na LCG. Esses resultados sugerem que o tecido adiposo pode não ser a principal fonte de RBP4.

INTRODUCTION: Previous studies have suggested that Retinol Binding Protein 4 (RPB4), a protein produced by the adipose tissue, is associated with insulin resistance (IR). Congenital Generalized Lipodystrophy (CGL) is a rare disease characterized by IR and paucity of adipose tissue. Our objective was to determine RBP4 levels in patients with CGL. SUBJECTS AND METHODS: Six (6) patients with CGL and a healthy control group were selected to participate in the study. Anthropometric and biochemical variables were compared between groups. RESULTS: No difference was observed in RBP4 levels between the two groups (CGL 42.5 [12.5 - 127] vs. control 57.4 [15.9 - 165]; p = 0.78). On the other hand, leptin levels were significantly lower in CGL patients (CGL 0.65 [0.2 - 0.7] vs. control 10.9 [0.9 - 38.6]; p = 0.015). No correlation was found between RBP-4 and waist circunference (r = 0.18, p = 0.57), or BMI (r = 0.24, p = 0.45). CONCLUSION: RBP4 is not decreased in CGL. These results suggest that adipose tissue may not be the main source of RBP4.

OBJETIVO: Avaliar o impacto dos sintomas depressivos e da dor neuropática na qualidade de vida (QV) de pacientes diabéticos com polineuropatia distal diabética (PNDD). MÉTODOS: Foram avaliados 204 pacientes com diabetes melito tipo 2. O diagnóstico de PNDD foi realizado por meio do Escore de Sintomas Neuropáticos e Escore de Comprometimento Neuropático. A gravidade da dor neuropática foi avaliada por meio da Escala Visual Analógica (EVA); os sintomas depressivos, por meio do Inventário Beck de Depressão (IBD); a QV, com o World Health Organization Quality of Life abreviado (WHOQOL-bref). RESULTADOS: Pacientes com PNDD apresentaram escores mais altos no IBD (12,6 ± 7,2 versus 9,9 ± 7,3; p = 0,018) e no EVA (5,0 ± 2,4 versus 2,6 ± 2,9, p < 0,001). Em relação à QV, apresentaram escores mais baixos no domínio físico (52,8 ± 15,5 versus 59,2 ± 17,0; p = 0,027) e ambiental (56,6 ± 12,3 versus 59,6 ± 13,6; p = 0,045). CONCLUSÕES: Pacientes diabéticos com PNDD apresentam pior QV nos domínios físico e ambiental do WHOQOL-bref, provavelmente devido à maior sintomatologia depressiva e gravidade de dor.

OBJECTIVE: To investigate the impact of depressive symptoms and neuropathic pain in the quality of life (QL) of diabetic patients with diabetic distal polyneuropathy (DDP). METHODS: Two hundred and four patients with type 2 diabetes mellitus were evaluated. The diagnosis of DDP was achieved using the Neuropathy Disability Score and Neuropathy Symptom Score questionnaires. The severity of neuropathic pain was assessed by means of a Visual Analogue Scale (VAS); the severity of depression, by means of the Beck Depression Inventory (BDI); and QL was assessed by means of the World Health Organization Quality of Life Instrument-bref (WHOQOLbref). RESULTS: Patients with DDP presented significant higher scores in BDI (12.6 ± 7.2 versus 9.9 ± 7.3; p = 0.018) and in VAS (5.0 ± 2.4 versus 2.6 ± 2.9; p < 0.001). They also presented significant lower scores in the physical (52.8 ± 15.5 versus 59.2 ± 17.0; p = 0.027) and environmental domains (56.6 ± 12.3 versus 59.6 ± 13.6; p = 0,045). CONCLUSIONS: Diabetic patients with DDP presented a worse QL in the physical and environmental domains of the WHOQOL-bref, probably due to more depressive symptoms and the severity of pain.

Embora existam recomendações especificas envolvendo o tratamento das dislipidemias em pacientes com alto risco, estas recomendações dificilmente são seguidas adequadamente. O objetivo deste estudo é investigar fatores de risco em pacientes com alto risco cardiovascular acompanhados ambulatorialmente no Brasil e Venezuela. Os prontuários de 412 pacientes foram selecionados em 4 instituições. Os pacientes foram divididos conforme a utilização de hipolipemiantes. Pacientes sem hipolipemiantes apresentavam níveis mais elevados de colesterol total (p< 0,001), LDL colesterol (p< 0,001) e HDL colesterol (p< 0,001), além de menores níveis de triglicérides (p< 0,001). O uso de hipolipemiantes foi associado à diminuição dos níveis de colesterol total (251,0 ± 40,0 para 196,0 ± 46,0), LDL colesterol (168,0 ± 36,0 para 116,0 ± 39,0), HDL colesterol (51,0 ± 46,0 para 46,0 ± 12,0) e triglicérides (181,0 ± 120,0 para 160,0 ± 79,0). Concluímos que apenas um pequeno percentual de pacientes, mesmo em uso de estatinas, apresenta níveis de colesterol compatível com os atualmente recomendados. Desta forma, embora as recomendações para tratamento das dislipidemias sejam bem conhecidas, um pequeno percentual de pacientes atinge os valores desejados de colesterol. É necessário um melhor controle dos níveis lipídicos dos pacientes, tanto através da utilização de doses maiores de estatinas como da utilização da associação de hipolipemiantes.

Although there are specific guidelines regarding the treatment of dyslipidemia in highly risk patients, these recommendations are usually inadequately followed. The aim of this study is to investigate risk factors in patients with increased cardiovascular risk currently treated in Brazil and Venezuela. Medical charts of 412 patients were selected in 4 institutions. Patients were divided into groups according to the use of lipid-lowering drugs (LLD), particularly statins. Patients who did not use LLD showed higher levels of total cholesterol (p< 0.001), LDL cholesterol (p< 0,001) and HDL cholesterol (p< 0.001), besides lower levels of triglycerides (p< 0.001). The use of statins was associated with a decrease in levels of total cholesterol (from 251.0 ± 40.0 to 196.0 ± 46.0), LDL cholesterol (from 168.0 ± 36.0 to 116.0 ± 39.0), HDL cholesterol (from 51.0 ± 46.0 to 46.0 ± 12.0) and triglycerides (from 181.0 ± 120.0 to 160.0 ± 79.0). Finally, only a small percentage of patients, even those under treatment with LLD, showed cholesterol levels according to currently available guidelines. Therefore, although the guidelines for the treatment of dyslipidemia are widely known, only a small percentage of patients achieve adequate levels of cholesterol. It is necessary to decrease lipid levels of these patients by increasing the dose of the statins or using a second drug.

A osteomalacia hipofosfatêmica é uma doença rara caracterizada por hipofosfatemia, níveis elevados de fosfatase alcalina e diminuição da densidade óssea. O tratamento é realizado com suplementação oral com fosfato e vitamina D e, nos casos de osteomalacia oncogênica, com a ressecção do tumor. Relatamos o caso de uma paciente que apresentou quadro de osteomalácia hipofosfatêmica de causa indeterminada. Apesar de extensivamente procurado, nenhum tumor produtor de substância hipofosfatêmica foi localizado. A paciente foi tratada como suplementação de fosfato e vitamina D por longo período, evoluindo com quadro de hiperparatireoidismo terciário. A retirada de três paratireóides não normalizou os níveis de PTH e a paciente recusou-se a continuar a investigação e o tratamento. Após dez anos de tratamento irregular, foi internada por insuficiência respiratória causada por colabamento do arcabouço costal e múltiplas fraturas, evoluindo para o óbito. Os autores discutem a relação entre osteomalácia e hiperparatireoidismo e o curso agressivo da doença.

Adult-onset hypophosphatemic osteomalacia is a rare disease characterized by hypophosphatemia, increased levels of alkaline phosphatase and decreased bone mass. Oral supplementation with phosphate and vitamin D is the main treatment and, in cases of oncogenic osteomalacia, tumor resection is mandatory. We report the case of a patient with hypophosphatemic osteomalacia of an unknown cause. Despite extensive search, no tumor was found. The patient was treated with phosphate for a long period and developed tertiary hyperparathyroidism. Serum PTH levels did not return to normal after surgical excision of three parathyroids and the patient refused to continue clinical investigation and treatment. After ten years absent from the hospital, during which medications were used irregularly, she was admitted with multiple fractures and respiratory insufficiency caused by severe thoracic deformities, and died. The authors discuss the relationship between osteomalacia and hyperparathyroidism and the aggressive course of the disease.

Já foi demonstrado que a resistência à insulina (RI) está associada com a estimulação de progenitores eritrocitários e com níveis aumentados de marcadores inflamatórios. Desta maneira, a RI pode também estar associada o aumento de hemácias e leucócitos. Esse estudo objetivou demonstrar que a RI está independentemente associada com a alteração de parâmetros hematológicos em uma amostra da população brasileira. Nós analisamos exames laboratoriais de 925 indivíduos, incluindo todos os dados de parâmetros hematológicos, resistência insulínica (homeostasis model assessment - HOMA) e níveis lipídicos. Informação demográfica incluiu idade e gênero. HOMA correlacionou-se positivamente com a contagem de eritrócitos (r= 0,17; p<0,001), a concentração de hemoglobina (r= 0,14; p<0,001), o hematócrito (r= 0,15; p<0,001) e a contagem de leucócitos (r= 0,17; p<0,01). Indivíduos no quartil superior de RI tinham níveis mais elevados de glicemia, insulina de jejum, triglicérides, hematócrito, hemoglobina e contagem de leucócitos e eritrócitos do que aqueles no quartil inferior. Em conclusão: a RI parece estar associada com alterações em diversos parâmetros hematológicos. Essa alterações hematológicas podem ser consideradas um achado indireto da síndrome de resistência insulínica.

It has already been demonstrated that insulin resistance (IR) is associated with the stimulation of erythroid progenitors and with increased levels of inflammation markers. Therefore, IR should also be associated with increased red blood cell (RBC) and white blood cell (WBC) count. The aim of this study is to demonstrate that IR is independently associated with altered hematological parameters in a Brazilian sample. We analyzed laboratorial exams from 925 subjects. All data on hematological parameters, insulin resistance (Homeostasis Model Assessment [HOMA]) and lipid levels were included in the analysis. Demographic information included age and gender. HOMA correlated positively with RBC (r= 0.17, p< 0.001), plasma hemoglobin concentrations (r= 0.14, p< 0.001), hematocrit value (r= 0.15, p< 0.001) and WBC (r= 0.17, p< 0.01). Subjects in the upper quartile of IR had higher levels of plasma glucose, fasting insulin, triglycerides, hematocrit, hemoglobin, RBC and WBC count than those in the lower quartile. In conclusion, IR seems to be associated with alterations in several hematological parameters. These hematological alterations may be considered an indirect feature of the IR syndrome.

O objetivo deste trabalho é traduzir para o português e avaliar a confiabilidade de uma escala para diagnóstico da polineuropatia distal diabética (PNDD). O processo de tradução e adaptação para o português das versões simplificadas do Escore de Sintomas Neuropáticos (ESN) e Escore de Comprometimento Neuropático (ECN) foi realizado conforme as orientações internacionais padronizadas. As escalas foram aplicadas por dois avaliadores em 57 pacientes diabéticos selecionados seqüencialmente. Foi utilizada a correlação de Spearman para avaliação da concordância inter-avaliador e o alfa de Cronbach para avaliação da consistência interna do ESN. Tanto a aplicação do ECN como do ESN apresentou uma boa concordância entre os avaliadores (r= 0,77, p< 0,0001 e r= 0,76, p< 0,0001, respectivamente). O ESN apresentou boa consistência interna (alfa= 0,74). O diagnóstico de PNDD, realizado através da combinação dos escores, também apresentou boa concordância (r= 0,63, p< 0,0001). As versões em português do ECN e do ESN se mostraram adequadas para o diagnóstico da PNDD na população avaliada.

The aim of this study was to translate into Portuguese and to assess the reliability of an instrument for the diagnosis of diabetic distal polyneuropathy (DPN). The process for translation and adaptation into Portuguese of the Neuropathy Symptom Score (NSS) and the Neuropathy Disability Score (NDS) was performed following internationally standardized procedures. The instruments were applied by 2 raters in 57 consecutive subjects. Spearman correlation was used to evaluate the reliability and Cronbachs' alpha to evaluate the internal consistency of the items. Both, ECN and ESN, showed a good reliability (r= 0.77, p< 0.0001 and r= 0.76, p< 0.0001, respectively). ESN showed a good internal consistency (alpha= 0.74). The diagnosis of DPN, defined as the combination of the two scores (ECN+ESN) also showed a good reliability (r= 0.63, p< 0.0001). The Portuguese versions of the ESN and the ECN seem to be adequate for the diagnosis of DPN in this population.