Protocolo Clínico e Diretrizes Terapêuticas (PCDT) de tratamento medicamentoso da obesidade em crianças e adolescentes com doze a vinte e um anos de idade no Estado de Goiás ­ versão janeiro de 2023 / Clinical Protocol and Therapeutic Guidelines (PCDT) for drug treatment of obesity in children and adolescents aged twelve to twenty-one years in the State of Goiás ­ January 2023 version

A obesidade é um transtorno crônico, complexo e multifatorial, envolve fatores ambientais, estilo de vida, hormonais e genéticos, acomete indivíduos de todas as idades e quanto mais cedo ocorre, maiores são os riscos à saúde. Uma criança com obesidade tem 80% chance de tornar-se um adulto com obesidade (FREEDMAN et al., 2007). Tratamento medicamentoso está aprovado a partir do IMC> 27 kg/m2 associado a comorbidades ou ≥ 30 kg/m2 mesmo na ausência de comorbidades. Liraglutida é o único medicamento aprovada para uso em adolescentes a partir dos 12 anos de idade com peso corporal maior que 60 kg e IMC correspondendo a 30 kg/m² para adultos

Liraglutida comparada a terapia padrão para o tratamento da obesidade: revisão rápida de evidências / Liraglutide compared to standard therapy for the treatment of obesity: rapid response review of evidence

Liraglutida e terapia padrão (modificação no estilo de vida, com dieta e prática regular de exercícios), como opção disponível no Sistema Único de Saúde. Indicação: Tratamento da obesidade. Pergunta: Liraglutida, comparada à terapia padrão, é mais eficaz e segura para promover redução do peso em pessoas adultas com obesidade? Métodos: Revisão rápida de evidências, revisão de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews version 2). Resultados: Foi selecionada uma revisão sistemática que atendeu aos critérios de inclusão. Conclusão: Liraglutida em dose ≤ 1,8 mg e em dose > 1,8 mg, comparadas a placebo (com terapia padrão) promoveram redução estatisticamente significativa de peso (-2,99 kg e -4,55 kg, respectivamente) e maior risco relativo de descontinuação do tratamento devido a efeitos adversos, com alta certeza de evidência para esses desfechos, além de maior risco relativo de náusea e de vômitos

Liraglutide and standard therapy (lifestyle modification, diet and regular exercise), as a option available in the Brazilian Public Health System. Indication: Treatment of obesity. Question: Is Liraglutide, compared to standard therapy, more effective and safer for weight reduction in obese adults? Methods: Rapid review of evidence, overview of systematic reviews, with a bibliographic search in the PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews version 2). Results: A unique systematic review that met the inclusion criteria was selected. Conclusion: Liraglutide at a dose ≤ 1.8 mg and at a dose > 1.8 mg, compared to placebo (and standard therapy) induced statistically significant weight reduction (-2.99 kg and -4.55 kg, respectively) and greater relative risk of treatment discontinuation due to adverse effects, with high certainty of evidence, and greater relative risk of nausea and vomiting

Liraglutide restores late cardioprotective effects of remote preconditioning in diabetic rats via activation of hydrogen sulfide and nuclear factor erythroid 2-related factor 2 signaling pathway

ABSTRACT Purpose The present study explored the influence of liraglutide on remote preconditioning-mediated cardioprotection in diabetes mellitus along with the role of nuclear factor erythroid 2-related factor 2 (Nrf2), hypoxia inducible factor (HIF-1α) and hydrogen sulfide (H2S). Methods Streptozotocin was given to rats to induce diabetes mellitus and rats were kept for eight weeks. Four cycles of ischemia and reperfusion were given to hind limb to induce remote preconditioning. After 24 h, hearts were isolated and subjected to 30 min of ischemia and 120 min of reperfusion on Langendorff system. Liraglutide was administered along with remote preconditioning. Cardiac injury was assessed by measuring the release of creatine kinase (CK-MB), cardiac troponin (cTnT) and development of left ventricular developed pressure. After ischemia-reperfusion, hearts were homogenized to measure the nuclear cytoplasmic ratio of Nrf2, H2S and HIF-1α levels. Results In diabetic rats, there was more pronounced injury and the cardioprotective effects of remote preconditioning were not observed. Administration of liraglutide restored the cardioprotective effects of remote preconditioning in a dose-dependent manner. Moreover, liraglutide increased the Nrf2, H2S and HIF-1α levels in remote preconditioning-subjected diabetic rats. Conclusions Liraglutide restores the lost cardioprotective effects of remote preconditioning in diabetes by increasing the expression of Nrf2, H2S and HIF-1α.

Use of flash glucose-sensing technology in patients with type 2 diabetes treated with liraglutide combined with CSII: a pilot study

Glycemic variability (GV) may be linked to the development of diabetic complications by inducing inflammation, oxidative stress, and endothelial dysfunction. Flash glucose monitoring (FGM) provides a novel method of continuously monitoring interstitial glucose levels for up to 14 days. This study randomly assigned poorly controlled type 2 diabetes mellitus patients treated with metformin and multiple daily injections of insulin (n=60) to either continuous subcutaneous insulin infusion (CSII) treatment or CSII in combination with liraglutide (CSII+Lira) treatment for 14 days during hospitalization. GV was assessed using a FGM system; weight and cardiometabolic biomarkers were also evaluated. The coefficient of variation was significantly reduced in the CSII+Lira group (P<0.001), while no significant change was observed in the CSII group. The changes differed significantly between the two groups in mean amplitude of glycemic excursions (P=0.004), standard deviation (P=0.006), and the percentage of time in the target range (4-10 mmol/L, P=0.005 and >10 mmol/L, P=0.028). The changes in mean of daily differences, interquartile range, and percentage of time in hypoglycemia (<3.3 mmol/L) and hyperglycemia (>13.9 mmol/L) identified by FGM showed no difference. Treatment with liraglutide increased serum adiponectin [33.5 (3.5, 47.7) pg/mL, P=0.003] and heme oxygenase-1 levels [0.4 (-0.0, 1.8) ng/mL, P=0.001] and reduced serum leptin levels [-2.8 (3.9) pg/mL, P<0.001]. Adding the glucagon-like peptide-1 analog liraglutide improved GV, weight, and some cardiometabolic risk markers. The FGM system is, therefore, shown to be a novel and useful method for glucose monitoring.

Understanding the Mechanism of Action and Clinical Implications of Anti-Obesity Drugs Recently Approved in Korea / 가정의학회지

The Korean Ministry of Food and Drug Safety has approved three anti-obesity drugs for long-term management in the past decade. In addition, since 2019, bariatric surgery has been financially supported by National Health Insurance Service in Korea. In this review, the mechanisms of action and the clinical implications of the recently approved anti-obesity drugs, lorcaserin, naltrexone/bupropion, and liraglutide are explained. Lorcaserin stimulates proopiomelanocortin (POMC)/cocaine- and amphetamine-regulated transcript (CART) neurons and inhibits neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons, which results in the activation of melanocortin 3/4 receptors. Naltrexone/bupropion stimulates POMC neurons through bupropion; this stimulation is augmented by blocking the autoinhibitory mechanism of POMC with naltrexone. The hypophagic effect of liraglutide is mediated through the direct activation of POMC/CART neurons and the indirect suppression of NPY/AgRP neurons through γ-aminobutyric acid-dependent signaling, with adjunctive suppression of the mesolimbic dopamine reward system. In addition to liraglutide, another glucagon-like peptide-1 receptor agonist, semaglutide, is expected to be added to the list of anti-obesity drugs in the near future. In patients with obesity and high cardiovascular risk, lorcaserin was considered neutral and liraglutide was considered favorable, whereas inconclusive results were obtained for naltrexone/bupropion.

Association Between Exercise and Treatment with Liraglutide in Obese Rats by Cafeteria Diet

Abstract The objective of this study was to evaluate the effect of liraglutide, an analog of glucagon-like peptide-1 (GLP-1) in association with physical exercise, on the metabolic and biochemical parameters of rats induced to obesity with a cafeteria diet. Male Wistar rats, aged 21 days, were randomly divided into: Controls (CON) receiving standard feed and water ad libitum; and obese (OBESE) receiving cafeteria diet ad libitum, added to the standard diet. Groups were then subdivided into: Liraglutide animals that received subcutaneous injections of liraglutide from 80 to 90 days of life; exercised (EXE) animals submitted to swimming sessions, three days a week (15 min); and liraglutide + EXE animals that received liraglutide in association with physical exercise. Treatment with liraglutide reduced deposits of mesenteric and periepididymal fat, HOMA-IR, triglycerides, glucose and insulin in obese group. It is important to note that the association of the two treatments reduced the body weight in animals, deposits of mesenteric and periepididymal fat, HOMA-IR, blood triglyceride levels, glucose and insulin in obese rats. As such, the association of liraglutide with exercise potentiated the effects of the drug and ameliorated obesity pathology more effectively. retirar

Eficacia y seguridad de la liraglutida como tratamiento coadyuvante para disminuir el índice de masa corpora / Efficacy and safety of liraglutide as a adjuvant treatment to reduce the body mass index / Eficácia e segurança do liraglutido como tratamento adjuvante para reduzir o índice de massa corpora

Introducción. El sobrepeso y la obesidad son condiciones que vienen en aumento en Colombia y en el mundo, lo cual es preocupante ya que gene-ran predisposición para enfermedades que causan alta morbimortalidad. El tratamiento para estas enfermedades necesita un enfoque multidiscipli-nario que incluya hábitos saludables con cambios en la dieta, aumento de la actividad física y, en ocasiones, uso de fármacos y cirugía bariá-trica como tratamiento coadyuvante. Algunos medicamentos GLP-1 han demostrado eficacia en la pérdida de peso, en especial la liraglutida, un medicamento usado como complemento de la dieta y el ejercicio para lograr mayor control glucémico en adultos con diabetes mellitus tipo 2 que también tienen enfermedad cardiovascular.Objetivo.Evaluar la eficacia y seguridad de la liraglutida como medica-mento coadyuvante para disminuir el índice de masa corporal (IMC) en personas con sobrepeso (IMC=25-30 kg/m2)y obesidad (IMC>30 kg/m2).Materiales y métodos. Se realizó una búsqueda en las bases de datos Trip Database, Embase, PubMed, Scopus y Clinical Key sobre estudios que cumplieran los criterios de inclusión y que evaluaran la disminución de peso con el uso de liraglutida. Conclusiones. La liraglutida es un medicamento que reduce el IMC en personas con sobrepeso y obesidad; sin embargo, presenta efectos ad-versos que deben ser evaluados, razón por la cual es necesario ampliar la literatura y las líneas de investigación para, de esta manera, tener evi-dencia clara con la cual sea posible discutir su eficacia y seguridad como tratamiento coadyuvante en personas con sobrepeso

Introduction: Overweight and obesity are two conditions that have been increasing in Colombia and worldwide, what is wo-rry in about this is the predispose that illness can cause high mortality and mobility. Treatment of overweight and obesity needs multidisciplinary approach in which should be included healthy habits with change in diet and increase physical activi-ty, sometimes the use of medications and bariatric surgery can be taken in mind as adjuvant therapy. Different characteristics have been demonstrated in medications like GLP-1 specially liraglutide for weight lossObjective: Evaluate the efficacy and safety of liraglutide as a adjuvant medication to reduce the body mass index (BMI) in overweight (BMI: 25-30 Kg / m2) and obesity (BMI:> 30 Kg / m2) worldwideMaterials and methods: We will search for studies in the di-fferent databases (TRIP, Embase, Pubmed, Scopus and Clini-calKey), which must meet inclusion criteria and evaluate weight reduction with the use of liraglutide.Conclusions: Liraglutide is a medicine that reduces BMI in people with overweight and obesity, however, it has adverse effects that must be evaluated. Therefore, the li-terature and lines of research should be expanded in the future; and in this way have clear evidence to discuss the efficacy and safety of liraglutide as a adjuvant treatment in overweight people.

Introdução. Sobrepeso e obesidade são condições que estão aumentando na Colômbia e no mundo, o que é preocupante, pois gera predisposição para doenças que causam alta mor-bimortalidade. O tratamento para essas doenças requer uma abordagem multidisciplinar que inclua hábitos saudáveis com mudanças na dieta, aumento da atividade física e, às vezes, uso de drogas e cirurgia bariátrica como tratamento adjuvante. Alguns medicamentos para o GLP-1 provaram ser eficazes na perda de peso, especialmente o liraglutido, um medicamento usado como complemento à dieta e ao exercício para obter maior controle glicêmico em adultos com diabetes mellitus tipo 2 que também apresentam doenças cardiovasculares.Objetivo. Avaliar a eficácia e segurança do liraglutido como medicamento adjuvante para reduzir o índice de massa corpo-ral (IMC) em pessoas com sobrepeso (IMC = 25-30 kg /m2) e obesidade (IMC> 30 kg /m2).Materiais e métodos. Pesquisamos os bancos de dados Trip Database, Embase, PubMed, Scopus e Clinical Key em estudos que atenderam aos critérios de inclusão e que avaliaram a per-da de peso com o uso de liraglutido.Conclusões. O liraglutido é um medicamento que reduz o IMC em pessoas com sobrepeso e obesidade; no entanto, apresenta efeitos adversos que devem ser avaliados, motivo pelo qual é necessário ampliar a literatura e as linhas de pesquisa para, dessa forma, ter evidências claras com as quais é possível dis-cutir sua eficácia e segurança como tratamento adjuvante em pessoas com excesso de peso.

Intentos para perder peso en una población con sobrepeso y obesidad referida a un centro de endocrinología en Colombia / Attempts to lose weight in an overweight and obese population referred to an endocrinology center in Colombia / Tentativas de perda de peso de uma população com sobrepeso e obesidade encaminhada para um centro de endocrinologia na Colômbia

Introducción. El exceso de peso es una condición prevalente en Colombia. Esto conlleva a realizar múltiples intentos para perder peso, muchos autodirigidos y con riesgos, siendo un motivo de consulta frecuente en atención médica primaria y especializada. Metodología. Estudio de corte transversal con datos secundarios de la consulta de endocrinología de pacientes que consultaron por percepción de aumento de peso. Se indagó por 18 métodos convencionales y populares para perder peso, su duración, peso perdido y posterior re ganancia. Resultados. Se incluyeron 100 personas, 79% mujeres, con un promedio de edad de 41.1 años, índice de masa corporal de 32.9 ± 4.6 kg/m2 y perímetro abdominal de 102.7 ± 12.5 cm. En promedio se registraron entre 4 y 5 intentos para perder peso por persona antes de consultar al endocrinólogo, con una mediana de historia de exceso de peso de 10 años. Todos los intentos lograron alguna pérdida con posterior reganancia del total del peso perdido, excepto liraglutida. No se encontró asociación significativa entre variables antropométricas y el número de intentos para perder peso. Discusión. Los intentos de pérdida de peso más empleados por la población evaluadas son los que no están aprobados o carecen de evidencia científica robusta. Conclusiones. Los pacientes con sobrepeso y obesidad realizan múltiples intentos fallidos para perder peso antes de consultar al médico especialista. La reganancia es muy frecuente, independientemente del tipo de intento. Cómo citar. Wandurraga EA, Marín Carrillo LF, Ardila Gutiérrez MA, Serrano-Gómez SE. Intentos para perder peso en una población con sobrepeso y obesidad referida a un centro de endocrinología en Colombia. MedUNAB. 2019:22(3): 314-321. doi: 10.29375/01237047.3569

Introduction. Excess weight is a prevailing condition in Colombia. This leads to many weight loss attempts, many self-managed and with risks, being a frequent reason for consulting primary and specialized healthcare. Methodology. Cross-sectional study with secondary data from the endocrinology consultation of patients who made the appointment due to a perceived increase in weight. Eighteen conventional and popular ways of losing weight, their duration, the weight lost and the subsequent regained weight were investigated. Results. One hundred people were included, 79% women with an average age of 41.1 years, a body mass index of 32.9 ± 4.6 kg/m2 and a waist circumference of 102.7 ± 12.5 cm. Each person reported an average of four to five attempts to lose weight before consulting the endocrinologist, with a median history of being overweight of ten years. All of the attempts achieved some weight loss with subsequent regain of the total weight lost, except when using liraglutide. A significant association was not found between the anthropometric variables and the number of weight loss attempts. Discussion. The weight loss methods most used by the assessed population are ones that are not approved or that lack strong scientific evidence. Conclusions. Overweight or obese patients make multiple failed attempts to lose weight before consulting a specialist physician. Regain of the lost weight is frequent, regardless of the method used. Cómo citar. Wandurraga EA, Marín Carrillo LF, Ardila Gutiérrez MA, Serrano-Gómez SE. Intentos para perder peso en una población con sobrepeso y obesidad referida a un centro de endocrinología en Colombia. MedUNAB. 2019:22(3): 314-321. doi: 10.29375/01237047.3569

Introdução. Excesso de peso é uma condição prevalecente na Colômbia. Isso leva a várias tentativas de perda de peso, muitas auto-dirigidas e de risco, sendo motivo de consultas frequentes em atendimento médico primário e especializado. Metodologia. Estudo transversal com dados secundários da consulta de endocrinología de pacientes que consultaram para percepção do ganho de peso. Foram investigados 18 métodos convencionais e populares para perder peso, sua duração, peso perdido e subsequente reganho. Resultados. Foram incluídas 100 pessoas, 79% mulheres, com idade média de 41,1 anos, índice de massa corporal de 32,9 ± 4,6 kg / m2 e perímetro abdominal de 102,7 ± 12,5 cm. Em média, foram registradas entre quatro e cinco tentativas de perda de peso por pessoa antes de consultar o endocrinologista, com uma mediana de história de excesso de peso de 10 anos. Todas as tentativas alcançaram alguma perda com subsequente re-ganancia do peso total perdido, exceto o liraglutida. Não foi encontrada associação significativa entre as variáveis antropométricas e o número de tentativas de perda de peso. Discussão. As tentativas de perda de peso mais utilizadas pela população avaliada são aquelas que não são aprovadas ou não possuem evidências científicas robustas. Conclusões. Pacientes com sobrepeso e obesos fazem várias tentativas fracassadas de perder peso antes de consultar o especialista. A re-ganancia de peso é frequente, independentemente do tipo de tentativa. Cómo citar. Wandurraga EA, Marín Carrillo LF, Ardila Gutiérrez MA, Serrano-Gómez SE. Intentos para perder peso en una población con sobrepeso y obesidad referida a un centro de endocrinología en Colombia. MedUNAB. 2019:22(3): 314-321. doi: 10.29375/01237047.3569

The Role of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Reducing Cardiovascular Events in Patients with Type 2 Diabetes

The prevalence of type 2 diabetes mellitus (T2DM), which is associated with cardiovascular morbidity and mortality, is increasing worldwide. Although there have been advances in diabetes treatments that reduce microvascular complications (nephropathy, neuropathy, retinopathy), many clinical studies have found that conventional oral hypoglycemic agents and glucose control alone failed to reduce cardiovascular disease. Thus, incretin-based therapies including glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT-2Is) represent a new area of research, and may serve as novel therapeutics for treating hyperglycemia and modifying other cardiovascular risk factors. Recently, it has been confirmed that several drugs in these classes, including canagliflozin, empagliflozin, semaglutide, and liraglutide, are safe and possess cardioprotective effects. We review the most recent cardiovascular outcome trials on GLP-1RAs and SGLT-2Is, and discuss their implications for treating patients with T2DM in terms of protective effects against cardiovascular disease.

Injectable Therapy for Diabetes Mellitus: Glucagon-Like Peptide-1 Receptor Agonist / 임상당뇨병

According to the American Diabetes Association (ADA) and the European Association for the Study of Diabetes guideline for treatment of diabetes, glucagon-like peptide-1 receptor agonist (GLP-1 RA) is recommended in diabetic patients with established atherosclerotic cardiovascular disease. This recommendation is based on the results of recent cardiovascular outcome trials of this kind of medications. GLP-1 RAs have a glucose lowering effect with weight loss and a lower incidence of hypoglycemia, and can improve cardiovascular outcomes such as three-point major cardiovascular events composed of death from cardiovascular causes, non-fatal myocardial infarction, and non-fatal stroke. Also, several GLP-1 RAs have beneficial effects on renal outcomes, mainly due to improvement in macroalbuminuria. In addition, high-dose liraglutide (3 mg/day subcutaneous injection) showed efficacy for reducing body weight. Therefore GLP-1 RA may be effective in patients with established cardiovascular disease, chronic kidney disease, and/or metabolic syndrome.

Mechanisms of action and clinical applications of anti-obesity drugs currently available in Korea

Over the last 5 years, the Korean Ministry of Food and Drug Safety has approved four anti-obesity drugs for long-term weight management. In this review, the mechanisms of action and clinical applications of lorcaserin, naltrexone/bupropion, liraglutide, and phentermine/topiramate have been clarified. Lorcaserin stimulates proopiomelanocortin/cocaine- and amphetamine-regulated transcript neurons in the arcuate nucleus. Naltrexone/bupropion reduces body weight by controlling the hedonic reward system of food intake. The hypophagic effect of liraglutide depends on the direct activation of the proopiomelanocortin/cocaine- and amphetamine-regulated transcript neurons and indirect suppression of neuropeptide Y/agouti-related peptide neurons through gammaaminobutyric acid-dependent signaling, with an additional thermogenic effect. Phentermine/topiramate induces weight loss by elevating the norepinephrine levels in the hypothalamus, reducing energy deposition in the adipose tissue and skeletal muscle, and elevating the corticotropin-releasing hormone in the hypothalamus. In patients with high cardiovascular risks or type 2 diabetes mellitus, lorcaserin and liraglutide are appropriate. In patients with mood disorders, naltrexone/bupropion could be considered as the first choice of therapy. Notably, lorcaserin and liraglutide are neutral in the aspect of sleep disorder. In case of obese individuals with obstructive sleep apnea, liraglutide or phentermine/topiramate would be selected as the treatment option. These four drugs should be used after considering the patients' co-morbidities of obesity.

Comparative study on anorexigenic effect of glucagon-like peptide-1 receptor agonists in rats / 生理学报

Glucagon-like peptide-1 (GLP-1) expression is shared by both intestinal cells and neurons of brainstem, which plays anorexigenic role on food intake. However, the exact source of physiological GLP-1 influencing food intake and pertinent mechanism of GLP-1 receptor agonists (GLP-1RA) remain unelucidated. In this study, the immediate early gene product c-Fos was chosen as the specific antigen for immunohistochemistry to show the certain areas of central nervous system (CNS) activation by the GLP-1RA. Thirty normal SD rats were randomly assigned to 3 groups, which were single intraperitoneally injected with Liraglutide (200 μg/kg), Exenatide (10 μg/kg) and saline, respectively. After injection, the amount of food intake and acute glycemic variation were assessed for comparison. The results showed that acute pharmacological dosage of GLP-1RA (Liraglutide or Exenatide) could significantly influence food intake. However, glycemic change indicated that the anorexic effect was dissociated with change in blood glucose in normal rats. Moreover, c-Fos was expressed significantly higher in major critical nuclei related to food intake in GLP-1RA groups when compared with the control group, and its expression was also found in spinal cord. The results suggested that acute administration of pharmacological doses of GLP-1 influences CNS via circulation and vagal pathways, especially on the arcuate nucleus (ARC) and the nucleus of solitary tract (NTS), and GLP-1 modulates autonomic nervous activities.

Normoglucemiantes orales y riesgo cardiovascular / Oral glucose-lowering drugs and cardiovascular risk

Resumen Introducción: la enfermedad cardiovascular es la principal causa de muerte en el mundo, así como la primera causa de morbilidad y mortalidad en pacientes con diabetes mellitus; por tanto, es importante conocer los diferentes medicamentos que existen hoy para el manejo de la diabetes mellitus y sus efectos, tanto positivos como negativos a nivel cardiovascular. De ahí que las diferentes sociedades y asociaciones científicas del mundo hayan emitido la recomendación de que todos los medicamentos para el tratamiento de la diabetes mellitus tipo 2 deben ser evaluados y certificados como seguros a nivel cardiovascular. Metodología: se hizo una búsqueda ampliada de la literatura existente acerca de los antidiabéticos actuales y sus efectos cardiovasculares. Resultados: existen diferentes tipos de medicamentos que se han relacionado con disminución o aumento del riesgo cardiovascular. En la actualidad hay evidencia que relaciona la metformina (biguanida), la empagliflozina (inhibidor del cotransportador sodio- glucosa 2) y la liraglutide (análogo de péptido similar al glucagón) con menos muerte cardiovascular y eventos cardiovasculares en pacientes con enfermedad cardiovascular establecida. Conclusión: los pacientes con enfermedad cardiovascular conocida pueden tener un beneficio adicional seleccionando medicamentos hipoglucemiantes con un mejor perfil de seguridad cardiovascular.

Abstract Introduction: Cardiovascular disease is the main cause of death worldwide, as well as the first cause of morbidity and mortality in patients with diabetes mellitus. For these reasons it is important to know the different drugs currently available to manage diabetes mellitus and their positive and negative effects at cardiovascular level. Hence, different scientific societies and associations of the world have issued the recommendation that all drugs for the treatment of type 2 diabetes mellitus must be evaluated and certified as safe at cardiovascular level. Methodology: An extensive search was carried out on the existing literature on current antidiabetic drugs and their cardiovascular effects. Results: There are different types of drugs that are associated with a decrease or increase in cardiovascular risk. Currently, there is evidence that associated metformin (biguanide), empagliflozin (sodium-glucose cotransporter 2 inhibitor), and liraglutide (a glucagon-like peptide analogue), with less cardiovascular deaths and cardiovascular events in patients with established cardiovascular disease. Conclusion: Patients with known cardiovascular disease may have an additional benefit in selecting glucose-lowering drugs with a better cardiovascular safety profile.

Eficacia y seguridad de IdegLira para la intensificación del tratamiento en la diabetes tipo 2 / Efficacy and safety of IdegLira for the intensification of type 2 diabetes treatment

La diabetes mellitus es una verdadera pandemia; la diabetes tipo 2 en particular, con su carácter progresivo, constituye un grave problema de salud. A pesar de los avances e innovaciones en el tratamiento, continúa generando una alta morbimortalidad, debido a que muchos pacientes no logran los objetivos de control metabólicos, entre otras causas por la inercia clínica, el temor a la hipoglucemia, el aumento de peso, la complejidad del tratamiento y la falta de adherencia al mismo. En el último tiempo, se ha evaluado con éxito los resultados clínicos del uso combinado de insulina basal y agonistas del receptor del péptido similar al glucagón tipo 1 (AR-GLP1). Se propone, por lo tanto, el uso combinado de una insulina basal (insulina degludec) con un AR-GLP1 (liraglutida), en un único dispositivo (IdegLira), como una alternativa terapéutica eficaz y segura para la intensificación del tratamiento de las personas con diabetes tipo 2. IdegLira ha demostrado mayores reducciones de HbA1c comparado con sus componentes individuales, con un bajo riesgo de hipoglucemia y pérdida de peso, tanto en pacientes naive de insulina como en aquellos previamente insulinizados. En esta revisión se describe la farmacología, el racional de la combinación y la evidencia clínica relevante de la seguridad y eficacia de IdegLira.

Diabetes mellitus is a true pandemic; type 2 diabetes in particular, with its progressive nature, constitutes a serious health problem. Despite advances and innovations in treatment, it continues to generate high morbidity and mortality.Many patients do not achieve their metabolic control objectives, due to clinical inertia, fear of hypoglycaemia, weight gain, the complexity of the treatment and the lack of adherence to it. Recently, the clinical results of the combined use of basal insulin and agonist receptor of the glucagon-like peptide type 1 (AR-GLP1) have been successfully evaluated. Therefore, the combined use of a basal insulin (insulin degludec) with an AR-GLP1 (liraglutide), in a single device (IdegLira), is proposed as an effective and safe therapeutic alternative for the treatment intensification in people with type 2 diabetes. IdegLira has shown greater reductions in HbA1c compared to its individual components, with a low risk of hypoglycaemia and weight loss, both in insulin naïve patients and in those previously insulinized. In this review we describe the pharmacology, the rational of the combination and the most relevant clinical evidence on IdegLira safety and efficacy.

The multicenter, open-Label, observational LEAD-Ph study: Real-world safety and effectiveness of liraglutide in Filipino participants with Type 2 Diabetes / Journal of the ASEAN Federation of Endocrine Societies

Objective@#Assess safety and effectiveness of liraglutide among Filipino participants with type 2 diabetes (T2D) in routine clinical practice.@*Methodology@#A 26-week, prospective, multicenter, open-label, observational study was conducted in adults with T2D prescribed liraglutide (1.2 mg or 1.8 mg) in routine clinical practice in the Philippines. Primary endpoint: incidence rate and type of serious adverse drug reactions (SADRs). Secondary endpoints included other aspects of safety, and effectiveness.@*Results@#Participants (n=1056) had a mean (standard deviation) age of 53.2 (12.0) years, and glycated hemoglobin (HbA1c) level of 8.8% (2.0). Of 19 ADRs reported in 17 participants, none were SADRs (primary endpoint). No serious adverse events were reported. From baseline to week 26: the proportion of participants with major hypoglycemic episodes (requiring assistance) decreased from 2.0% to 0.2%; and with minor episodes (plasma glucose <3.1 mmol/L [<56 mg/dL]) decreased from 6.1% to 1.5%; serum creatinine remained unchanged. Among secondary effectiveness endpoints, improvements were seen from baseline to week 26 in HbA1c level, fasting and postprandial blood glucose levels, body weight, blood pressure, and fasting lipid profile.@*Conclusion@#During routine clinical use of liraglutide for T2D in the Philippines, no new safety concerns were identified and blood glucose was lowered effectively.

Grandes estudos clínicos que demonstraram redução de risco cardiovascular através do uso de antidiabéticos / Large clinical trials that demonstrated a decrease in cardiovascular risk through the use of antidiabetics

Nos últimos anos, os avanços nas descobertas da terapêutica para o DM2 entusiasmaram os clínicos e especialistas no que diz respeito à redução dos eventos cardiovasculares, internações e mortalidade. Outros estudos ainda estão em andamento e prometem fortalecer a expectativa de mudança nos desfechos cardiovasculares dessa população. O objetivo dessa revisão consiste em reunir os principais estudos clínicos que demonstraram a segurança e/ou redução na ocorrência de eventos cardiovasculares com uso de fármacos anti-hiperglicemiantes.

In recent years, breakthroughs in therapeutic findings for DM2 have encouraged physicians and specialists with regards to the reduction of cardiovascular events, hospitalization and mortality. Other studies are underway, and promise to strengthen the prospects of change in cardiovascular outcomes for this population. The goal of this review is to bring together the most important clinical trials that have demonstrated safety and/or a decrease in cardiovascular events with the use of antihyperglycemic drugs.

Recent Advances in Anti-Obesity Agents / 대한내과학회지

Obesity is a chronic disorder that is a significant risk factor for diabetes, cardiovascular diseases, malignancy, and other chronic diseases. Lifestyle modifications form the basis of most treatments for obesity, but it has become clear that such modifications alone are not enough for many obese patients. When a behavioral approach is insufficient, pharmacological treatment may be recommended. In recent years, the US Food and Drug Administration (FDA) has withdrawn several therapeutic options for obesity due to their side effects, but has approved four novel anti-obesity agents. Until recently, orlistat was the only drug approved for the management of long-term obesity, but the US FDA approved the novel anti-obesity drugs lorcaserin and phentermine/topiramate in 2012, and naltrexone/bupropion and liraglutide in 2014. The present review discusses the different pharmacotherapeutic options for the treatment of obesity.

Cardiovascular Outcome Trials of Incretin Therapy (Dipeptidyl Peptidase-4 Inhibitors/Glucagon-Like Peptide-1 Receptor Agonist)

In 2008, the United States Food and Drug Administration issued guidance which mandated long-term cardiovascular outcome trials (CVOTs) to assess the safety of new antidiabetic drugs for type 2 diabetes. Since 2008, three CVOTs that have studied dipeptidyl peptidase-4 (DPP-4) inhibitors and four CVOTs of a glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) have been reported. Each of the completed CVOTs showed the noninferiority of respective drugs to placebo for primary CV composite endpoint. Among them, liraglutide and semaglutide showed a reduction of major adverse cardiovascular events. However, the mechanisms for the observed cardiovascular differences between DPP-4 inhibitors and GLP-1RA, and across individual GLP-1RA are not clearly understood. Therefore, this review will summarize the CVOTs of the DPP-4 inhibitors and GLP-1RA, interpretation of cardioprotective results of incretin-based therapy and the possible mechanism of action.

Uso de análogo de GLP-1 na hipoglicemia pós prandial em paciente submetido a cirurgia bariátrica: relato de caso / Use of GLP-1 analogue in postprandial hypoglycemia in patient undergoing bariatric surgery: case report

RESUMO O baypass gástrico em Y de Roux(GYR) é um dos principais procedimentos utilizados para tratamento da obesidade quando dieta e medição não funcionam, porém a longo prazo pode levar a uma complicação rara e de etiologia ainda imprecisa, a Hipoglicemia pós-prandial (HPP). Surge 1 a 3 anos após o procedimento, acredita-se que em reposta ao aumento da secreção de GLP-1 e consequente aumento de insulina, levando a hipoglicemia. É percebido na maioria das vezes na presença de alguns sintomas, como tontura, fadiga, fraqueza, sudorese, entre outros; com a detecção de hipoglicemia no momento, e melhora após consumo de carboidrato, podendo ser realizados exames posteriormente para confirmação. O tratamento inicial pode ser feito com uma dieta restrita em carboidrato, podendo ser associado medicação, entre elas, o análogo de GLP-1, medidas mais invasivas, como pancreatectomia são utilizadas em casos refratários ou com sintomas mais graves. Foi utilizado Victoza no tratamento de uma paciente que desenvolveu HPP um ano e meio após cirurgia, com sintomas principalmente após o janta, realizou-se teste oral de tolerância a glicose com e sem o uso da medicação, sendo comprovado a eficácia do tratamento com ausência de hipoglicemia no primeiro teste, e 2 episódios de hipoglicemia e aumento de curva de insulina na segunda etapa. Palavras-chave: cirurgia bariátrica, hipoglicemia, liraglutida