Cost-effectiveness analysis of once-weekly semaglutide vs. once-daily liraglutide administered subcutaneously in patients with overweight and obesity: a decision analysis.

OBJECTIVE: Obesity presents an enduring and multifaceted dilemma that impacts individuals, society, economies, and healthcare systems alike. Glucagon-like peptide-1 (GLP-1) receptor agonists, including liraglutide and semaglutide, have received FDA approval for obesity treatment. This study aims to present a cost-effectiveness analysis to compare the cost and clinical outcomes of semaglutide vs. liraglutide on weight loss in people with overweight and obesity. MATERIALS AND METHODS: A cost-effectiveness analysis was conducted to compare the cost and the clinical outcomes of adding weekly 2.4 mg SC semaglutide vs. daily 3.0 mg SC liraglutide or placebo to physical activity and diet control in overweight and obese patients. A clinical outcome of achieving ≥15% weight loss was chosen. A simple decision analysis model from a third-payer perspective was applied. Drug costs were based on the retail price of the USA market. One-way sensitivity analyses were performed. RESULTS: Results showed that 2.4 mg weekly semaglutide, when added to physical activity and diet control, was the most cost-effective choice in terms of ≥15% weight loss (ICER: $ 7,056/patient/68 weeks). The model was robust against the 50% increase in the unit cost of semaglutide and the 50% decrease in the unit cost of liraglutide, as well as the changes in probabilities by the corresponding 95% confidence intervals across the model. CONCLUSIONS: This cost-effectiveness analysis suggests that employing once-weekly 2.4 mg semaglutide emerges as a remarkably cost-effective option when contrasted with once-daily 3.0 mg liraglutide in patients with overweight and obesity when added to physical activity and diet control.

Assessment of the potential effects of l-carnitine and cinnamon supplementation on weight loss and body composition.

OBJECTIVE: Aim: To assess efficacy of L-carnitine and cinnamon alone and in combination on body composition parameters in addition to compare between them. PATIENTS AND METHODS: Materials and Methods: Sample of 28 obese and overweight adults in Babylon city, sample collection includes patients in places, or by internet, where interview take place according to specialize questionnaire height, weight, and body mass index were measured. RESULTS: Results: A significant differences P<0.05 among gender distribution between male and female. A significant difference between (150-160 cm, 160-170 cm) as compared with (170-180 cm, 180-190 cm). A significant difference between 170-180 cm as compared with 180-190 cm but non-significant differences between 150-160 cm as compared with 160-170 cm. A significant difference between 26-35 as compared with 36-45, 46-55, but non-significant differences between 36-45 as compared with 46-55. A significant difference between body weight, body fat, water content, skeletal muscle, and body mass index after treatment, but non-significant differences between protein, and inorganic salt after treatment and at baseline. A significant difference between body weight, water content, skeletal muscle, and body mass index in group treated with cinnamon as compared with negative control group, but non-significant differences between body fat, protein, and inorganic salt as compared with negative control group. CONCLUSION: Conclusions: The prevalence of overweight and obesity within accepted range of that reported in Iraq, important relationship was reported between several life style risk factor, as soon as diagnose increase in weight and education health program for behavior of life style were high recommended.

Tildrakizumab: the value of a personalized and flexible approach for treating moderate-to-severe plaque psoriasis in patients with high body weight or high disease burden.

INTRODUCTION: The introduction of biologics for the treatment of plaque psoriasis is one of the major therapeutic advances of the last decades in dermatology. The efficacy of this class of drugs can be influenced by multiple factors including obesity, being overweight, prior treatment failures, and disease severity. AREAS COVERED: Most of the currently available approved biologics are limited by their lack of dosing flexibility for adapting the therapy to the complexity of real-world patients with psoriasis. Among the class of anti-interleukin-23, tildrakizumab allows a greater dosing flexibility, increasing clinical benefits of patients with high burden of the disease or body weight >90 kg. EXPERT OPINION: This meta-opinion discusses the clinical data that were foundational for tildrakizumab dosage flexibility, elaborates on the definition of high burden of disease specifically linked to tildrakizumab dosage, and profiles the ideal patient that could benefit from treatment with the higher approved tildrakizumab dosage of 200 mg.

Evaluación clínica y económica de análogos del GLP-1 para el tratamiento del sobrepeso / Clinical and economic evaluation of GLP-1 analogues for the treatment of overweight

CONTEXTO: El sobrepeso y la obesidad constituyen un importante problema de salud pública en todo el mundo. El tratamiento inicial consta de modificación del estilo de vida (LSM, por sus siglas en inglés) y en caso de falla, se inicia con tratamiento farmacológico como semaglutida, la cual está aprobada por agencias regulatorias internacionales y nacionales para el sobrepeso con un IMC de ≥ 25 kg/m2 a ≤ 29.9 kg/m2 y la obesidad con un IMC ≥ 30 kg/m2. El objetivo de este informe es revisar la eficacia clínica, la seguridad y la costo-efectividad de semaglutida en comparación con liraglutida para el tratamiento del sobrepeso y obesidad en la población en edad adulta sin Diabetes Mellitus tipo 2 (DM2). Ambos medicamentos cuentan con registro sanitario expedido por la Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) para el tratamiento del sobrepeso y obesidad en la población en edad adulta, así como para el tratamiento de la DM2; sin embargo, en el Compendio Nacional de Insumos para la Salud (CNIS), se encuentran disponibles solamente para el tratamiento de la población en edad adulta con DM2. MÉTODOS: Se realizó una búsqueda sistemática de la literatura en diversas bases de datos. Se seleccionaron 13 documentos relevantes (2 revisiones sistemáticas [RS] con metanálisis en red [NMA, por sus siglas en inglés], 5 ensayos clínicos aleatorios [ECAs], 3 evaluaciones económicas y 3 evaluaciones de tecnologías para la salud). Las medidas de resultado fueron el cambio del peso corporal, porcentaje de eventos adversos (EAs), costos y la razón costo-efectividad incremental (RCEI). RESULTADOS: En la RS con NMA de Smith et al. (2022)2 , los resultados mostraron que, en pacientes en edad adulta con sobrepeso y obesidad, sin DM2 y con LSM, la diferencia porcentual del cambio en el peso desde el estado basal con semaglutida versus liraglutida fue de -7.02 (intervalo de confianza [IC] del 95%: - 9.61 a -4.41, 23 de 32 puntos del PRISMA NMA con un riesgo de sesgo alto) y con respecto a placebo, la diferencia porcentual fue de -12.43 (IC del 95%: -14.51 a -10.38). Los resultados para la RS con NMA de Vosoughi et al. (2021)3 , en esta misma población, indica que la diferencia de medias (DM) del cambio en el peso desde el estado basal con semaglutida versus liraglutida fue de -5.53 (IC del 95%: -7.45 a - 3.60, en 4 estudios, 52 semanas de seguimiento, con 29 de 32 puntos del PRISMA NMA con un riesgo de sesgo alto) y en la escala SUCRA semaglutida obtuvo una clasificación del 100%, lo que indica que refleja una mayor probabilidad de ser más efectiva en términos de pérdida de peso y con una menor probabilidad de presentar EAs. CONCLUSIONES: Los 5 ECAs4­8 , concluyeron que semaglutida, a una dosis de mantenimiento de 2.4 mg, presentó mayor eficacia frente a liraglutida 3.0 mg (dosis de mantenimiento) y placebo, y con una seguridad similar a la esperada en el grupo de los análogos del péptido similar al glucagón tipo 1 (GLP-1). En dos evaluaciones económicas9,10 se indicó que semaglutida fue costo-efectiva versus sus respectivos comparadores. En Kim et al. (2022) 9 los comparadores utilizados fueron ningún tratamiento, dieta y ejercicio (D&E), liraglutida 3.0 mg, fentermina/topiramato y naltrexona/bupropión; mientras que en Olivieri et al. (2022) 10 los comparadores considerados fueron D&E sola, liraglutida 3.0 mg, orlistat y naltrexona 32 mg/bupropión. Sin embargo, un tercer estudio11 mostró que semaglutida no fue costo-efectiva dados los umbrales de disposición a pagar aceptados. Los hallazgos deben interpretarse con cautela considerando las limitaciones tanto clínicas como económicas. Se requieren más estudios de semaglutida que investiguen sobre los efectos a largo plazo, estudios directos versus otras opciones de tratamiento farmacológico, y el efecto en las comorbilidades y mortalidad, con el objetivo de comprender de una mejor manera la eficacia, seguridad y costo-efectividad de semaglutida en el tratamiento de pacientes en edad adulta con sobrepeso y obesidad. De acuerdo al análisis crítico la evidencia clínica fue predominantemente de baja certeza según GRADEpro, además de un riesgo de sesgo muy serio. Con respecto a los estudios de evaluación económica, la evidencia mostró que semaglutida 2.4 mg vía SC una vez a la semana como complemento a la LSM, fue más eficaz, segura y costo-efectiva en comparación con liraglutida 3.0 mg más LSM y LSM en la población de participantes con sobrepeso y obesidad sin DM2; de acuerdo a la disponibilidad a pagar que se describe en los estudios.

Aframomum melegueta Seed Extract with Standardized Content of 6-Paradol Reduces Visceral Fat and Enhances Energy Expenditure in Overweight Adults - A Randomized Double-Blind, Placebo-Controlled Clinical Study.

Purpose: Aframomum melegueta (grains of paradise) seeds have been demonstrated to possess thermogenic potential. However, it is necessary to validate the functional attributes of A. melegueta seed extract in human subjects. Methods: In a double-blind, placebo-controlled clinical trial design, we have examined the thermogenic effects of a standardized A. melegueta seed extract (AfperFit). A total of 70 overweight male and female subjects (BMI ≥25.0 to ≤30.0 kg/m2) aged 20-50 years were enrolled and administered with either 250 mg of AfperFit or placebo in capsule form twice daily for 12 weeks. The primary efficacy endpoints included energy expenditure (indirect calorimetry), body composition (dual-energy X-ray absorptiometry (DEXA)) and fat distribution (computed tomography (CT scan)), analyzed at baseline and after 12 weeks of treatment. The effect of intervention on the quality of life was examined using SF-12 questionnaire. Results: Consumption of AfperFit significantly increased the energy expenditure (p<0.01), visceral fat area (p<0.001) and visceral to subcutaneous fat ratio (p<0.01) compared to placebo group. Consequently, there was significant body weight loss and reduction in BMI of subjects in AfperFit group compared to placebo (p<0.01). The safety evaluation showed that biochemical and hematological parameters were in the normal range. Supplementation of AfperFit was well tolerated during the study and no adverse effects were observed. Conclusion: Overall, this study validates the health benefits of A. melegueta seed extract as fat burner and recommends its use as a functional ingredient to improve the quality of life and general health.

Antiobesity Medication Use Among Overweight and Obese Adults in the United States: 2015-2018.

OBJECTIVE: To estimate the utilization of U.S. Food and Drug Administration- approved prescription antiobesity medications (AOMs) and to identify factors associated with AOM use in the United States. METHODS: Respondents aged ≥18 years meeting AOM eligibility criteria in the 2015-2016 and 2017-2018 National Health and Nutrition Examination Survey and the 2016 Medical Expenditure Panel Survey were included in the study. AOM eligibility was defined as having a body mass index (BMI) of ≥30 kg/m2 or having a BMI between 27 and 29.9 kg/m2 and at least 1 obesity-related comorbidity. Demographic, socioeconomic, and clinical characteristics, economic outcomes, and health-related quality of life were summarized and compared between AOM users and nonusers. Multivariable logistic regression was used to identify factors that were associated with AOM use. RESULTS: Only 0.80% of eligible adults reported using AOMs in the past 30 days in 2015-2016 and 2017-2018 National Health and Nutrition Examination Survey. A greater proportion of current AOM users previously tried dietary changes compared with nonusers. They also reported an average weight loss of 3.1 kg over the previous year compared with a 1.5-kg gain among the nonusers. The total health care costs trended higher among AOM users, driven mostly by higher outpatient service costs. A BMI of ≥30 kg/m2, depression, dyslipidemia, and infertility predicted AOM use, whereas Medicare and being at risk of sleep apnea were associated with lower odds of AOM use. CONCLUSION: Despite the availability of newer AOMs and their inclusion in medical treatment guidelines, the utilization of AOMs remains low. This may reflect under-prescribing of and/or restricted patient access to approved evidence-based pharmacotherapy for obesity.

[The assessment of renal function during the therapy of arterial hypertension with azilsartan medoxomil in patients with obesity or overweight and concomitant metabolic disorders].

AIM: To assess the influence of the therapy of arterial hypertension with azilsartan medoxomil on the renal function in overweight or obese patients with concomitant metabolic disorders. MATERIALS AND METHODS: An international multicenter observational nonintervention prospective study included 1945 patients, taking azilsartan medoxomil in accordance with approved prescribing information. The observation period reached 6 months. RESULTS: In patients with an initial glomerular filtration rate (GFR)60 ml/min/1.73 m2 or 60 ml/min/1.73 m2 mean change in systolic blood pressure after 6 months of therapy reached -32.511.1 and -30.413.6 mmHg, correspondingly, while the change in diastolic blood pressure was -13.78.8 and -14.29.4 mmHg, respectively. No decrease in renal function was observed. Moreover, in patients with an initial GFR60 ml/min/1.73 m2 GFR increased significantly (p0.001). CONCLUSION: Azilsartan medoxomil, prescribed as monotherapy or in free combinations, provided an effective control of blood pressure in patients with arterial hypertension with both normal or moderately reduced and initially significantly reduced renal function. High efficacy and acceptability of the drug was associated with a beneficial effect on renal function, which allows to consider azilsartan medoxomil as the drug of choice for the treatment of hypertension in patients with concomitant metabolic disorders.

Naltrexona/Bupropión en sobrepeso y obesidad / Naltrexone/Bupropion in overweight and obesity

CONTEXTO CLÍNICO: El sobrepeso y la obesidad se definen como una acumulación anormal o excesiva de grasa que puede ser perjudicial para la salud. El índice de masa corporal (IMC) es un indicador simple de la relación entre el peso y la talla que se utiliza frecuentemente para identificar el sobrepeso y la obesidad en los adultos. A partir del mismo, la Organización Mundial de la Salud (OMS) define sobrepeso a un IMC entre 25 y 29,9 kg/m2, obesidad grado I entre 30 y 34,99 kg/m2, obesidad grado II entre 35 y 39,99 kg/m2 y obesidad grado IV un IMC superior a 40 kg/m2. En el caso de niños y adolescentes, es necessário considerar la edad, el sexo y los patrones de crecimiento debido a que cambian la proporción del peso y la talla. El sobrepeso y la obesidad constituyen el sexto factor principal de riesgo de muerte en el mundo, generando el fallecimiento de alrededor de 3,4 millones de personas adultas por año. Según la OMS, en el año 2016 el sobrepeso y obesidad afectaron a 1,9 mil millones de personas adultas, de las cuales, aproximadamente 650 millones eran obesas. Las Naciones Unidas propusieron en sus objetivos de desarrollo sustentable reducir para el año 2030 en un tercio las muertes prematuras por enfermidades no transmisibles a través de la prevención, el tratamiento y la promoción del bienestar y la salud mental. En el caso de la obesidad las mejores intervenciones a nivel social tienen que ver con mejorar los niveles de actividad física en la población a través de la educación y reducir la exposición a dietas no saludables, a través de reformulación de alimentos y etiquetado, mejorar los ambientes físicos y la educación. TECNOLOGÍA: La naltrexona es un antagonista opioide y el bupropión es un antidepresivo con efectos inhibitorios débiles sobre la recaptación neuronal de dopamina y norepinefrina. El uso de esta combinación se sugiere que actúa regulando la ingesta de alimentos al aumentar la tasa de activación de las neuronas hipotalámicas (centro regulador del apetito) y circuito mesolímbico de dopamina (sistema de recompensas). El efecto neuroquímico exacto que conducen a la pérdida de apetito no estácompletamente comprendido. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de naltrexona/bupropión en sobrepeso u obesidad. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron una RS, siete RS con MA, tres GPC, cuatro ETS y diez informes de políticas de cobertura de naltrexona en combinación con bupropión a dosis fijas en sobrepeso y obesidad. No se halló evidencia de estudios controlados aleatorizados que evalúe la combinación de naltrexona/bupropión en población pediátrica, como tampoco estudios que la comparen en forma directa con otros tratamientos farmacológicos o quirúrgicos. Todos los estudios incluidos evalúan tratamiento con naltrexona/bupropión frente a placebo, ambos grupos acompañados con dieta hipocalórica y un aumento del ejercicio físico, en adultos con sobrepeso con un IMC de entre 27 y 29,9 kg/m2 u obesidad con un IMC mayor a 30 kg/m2 y por lo menos un factor de riesgo cardiovascular adicional. CONCLUSIONES: No se identificaron estudios que comparen en forma directa el tratamiento com naltrexona/bupropión con otras opciones farmacológicas o quirúrgicas en sobrepeso u obesidad. Evidencia de alta calidad muestra que el tratamiento naltrexona/bupropión, acompañado con dieta hipocalórica y un aumento del ejercicio físico, reduce de manera clínicamente relevante el peso corporal en adultos con sobrepeso (IMC de entre 27 y 29,9 kg/m2) u obesidad (IMC mayor a 30 kg/m2) y al menos un factor de riesgo cardiovascular adicional a corto y mediano plazo. Sin embargo, no hay evidencia que esta asociación mejore de manera clínicamente relevante las consecuencias clínicas y metabólicas asociadas al sobrepeso, y existe incertidumbre sobre su seguridad cardiovascular a largo plazo. Una guía de práctica clínica y un consenso de expertos proveniente de países de altos ingresos mencionan a esta asociación como una opción posible en la población mencionada, mientras que una guía de práctica de Argentina no la menciona. La mayoría de las políticas de cobertura del mundo relevadas no mencionan ni recomiendan esta asociación, y solo dos la evalúan y explícitamente no la cubren debido a la incertidumbre sobre su efectividad y seguridad a largo plazo. Dos estudios de costo-efectividad proveniente de países de altos ingresos consideran que existe incertidumbre sobre su costo-efectividad e impacto presupuestario. No se encontraron estudios locales que evalúen la dimensión económica.

Orlistate para a redução de peso em indivíduos com sobrepeso ou obesidade / Orlistat for weight reduction in overweight or obese individuals

CONTEXTO: O objetivo do presente relatório é analisar as evidências científicas sobre o uso do orlistate na redução de peso em pacientes com sobrepeso ou obesidade. PERGUNTA: Qual a eficácia e a segurança do orlistate na perda de peso? TECNOLOGIA: Orlistate. EVIDÊNCIAS CIENTÍFICAS: Por meio das estratégias de busca, nas bases Medline (via Pubmed) e Embase, foram recuperadas 15 revisões sistemáticas, que incluíram no total 88 ensaios clínicos randomizados (ECR) e mais 6 ECR não contemplados nas revisões. A evidência recuperada revela uma diferença média de emagrecimento de 2-3kg num período de ao menos seis meses com a utilização do orlistate em relação ao placebo ou a cuidados/aconselhamentos mínimos. Essa magnitude de efeito foi estatisticamente significativa em quase todos os estudos; porém, a perda de peso pós seguimento foi inferior a 5-10%, que é o limiar de perda de peso clinicamente significante. Somado a isso, houve aumento estatisticamente significativo de efeitos adversos gastrointestinais e altas taxas de abandono nos estudos avaliados. A evidência de maior qualidade recuperada aponta apenas para uma tendência de emagrecimento de 5-10% do peso com o uso de orlistate quando combinado às intervenções comportamentais, o que sugere que o tratamento farmacológico não deve ser implementado isoladamente na ausência de outras medidas não farmacológicas. ANÁLISE DE CUSTO-EFETIVIDADE: O uso do orlistate associado à dieta e exercício físico comparado a medidas não farmacológicas isoladas (sem intervenção farmacológica ou placebo associados à dieta e ao exercício físico) resultou em custo incremental de R$ 1.512,00 e efetividade incremental de 0,18 por paciente (18% a mais de probabilidade de redução de 10% do peso corporal basal no grupo que recebeu o orlistate). Deste modo, a RCEI foi de R$ 8.400,00 para cada paciente adicional com perda ponderal ≥ 10%. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Considerando a alta prevalência de sobrepeso e obesidade, a incorporação do orlistate resultaria em grande impacto orçamentário, o que demandou a realização de diferentes cenários na AIO. Inicialmente foram realizados 4 cenários: no cenário 1, em que 100% dos pacientes têm acesso e utilizam orlistate (120 mg, 3 vezes ao dia), o impacto em cinco anos seria de R$ 660.229.935.815,52. No cenário 2, em que o acesso e uso do medicamento são variáveis, de 30 a 50%, o impacto orçamentário seria de R$ 264.789.501.395,83 ao final de cinco anos. Dois cenários foram realizados utilizando-se a população de pacientes obesos, com doença cardiovascular e diabetes associados, considerando-se o acesso de 30 a 50% (cenário 3) e de 100% (cenário 4), respectivamente; o impacto orçamentário variou de R$ 69.260.107.248,44 (30 a 50 %) a R$ 172.694.143.544,81 (100 %), em 5 anos. Por fim, dois novos cenários foram elaborados, com populações diferentes; o cenário 5, considera todos os indivíduos com sobrepeso ou obesidade; o cenário 6, os indivíduos com sobrepeso ou obesos portadores de DM e DCV. Ambos os cenários utilizam variáveis como: o acesso de 100% dos elegíveis ao orlistate; o menor valor de orlistate em compras públicas; os que atingiram percentual de eficácia (perda de peso significativa; ou seja, > 10% do peso corpóreo) e de adesão (taxa de persistência de 6% por ano). Nesses cenários, o impacto orçamentário seria de R$ 128.219.321.588,43 e de R$ 32.611.780.932,25, ao final de cinco anos, respectivamente. CONSIDERAÇÕES GERAIS: A evidência científica analisada revela o emagrecimento de 2 a 3 kgs de peso corporal, em período de ao menos seis meses, com a utilização de orlistate em relação ao placebo ou a cuidados/aconselhamentos mínimos (o que não pode ser considerado como perda de peso clinicamente relevante). Há, em contraposição, aumento estatisticamente significativo de eventos adversos gastrointestinais e altas taxas de abandono nos estudos avaliados devido a estes eventos. Por se tratar de doença prevalente, o uso de orlistate em indivíduos com sobrepeso ou obesos ocasionaria alto impacto orçamentário no SUS, mesmo utilizando-se população restrita e os melhores resultados de eficácia e adesão ao tratamento. A análise inicial mostra que a possibilidade de uso seria como adjuvante em individuos refratários a tentativas de emagrecimento com intervenções baseadas no estilo de vida, considerando-se os resultados de eficácia encontrados e o alto impacto orçamentário estimado. CONSULTA PÚBLICA: Foram recebidas 39 contribuições, sendo 12 técnico-científicas e 27 contribuições de experiência ou opinião. A maioria discordou totalmente com a recomendação da Conitec, sendo os principais argumentos a ausência de tratamento farmacológico no SUS, a efetividade e a segurança do orlistate e o benefício clínico do medicamento em comorbidades como hipertensão e diabetes. RECOMENDAÇÃO FINAL: Os membros da Conitec presentes na 86ª reunião ordinária, deliberaram, após análise das contribuições recebidas, por recomendar a não incorporação do orlistate para a redução de peso em indivíduos com sobrepeso ou obesidade. Foram considerados a baixa eficácia; eventos adversos e alto impacto orçamentário. Foi assinado o Registro de Deliberação nº 514/2020. DECISÃO: não incorporar o orlistate para a redução de peso em indivíduos com sobrepeso ou obesidade, no âmbito do Sistema Único de Saúde - SUS, conforme a Portaria nº 14, publicada no Diário Oficial da União nº 78, seção 1, página 221, em 24 de abril de 2020.

Intranasal glucagon acutely increases energy expenditure without inducing hyperglycaemia in overweight/obese adults.

AIM: To assess the acute effects of 0.7 mg intranasal glucagon (ING) vs intranasal placebo (INP) on food intake and resting energy expenditure (REE). METHODS: A single-blind, crossover study was conducted in 19 overweight/obese adults (15 men, 4 women). REE was assessed by indirect calorimetry over 90 minutes, after which appetite was assessed using a visual analogue scale, and ad libitum caloric intake was assessed. Plasma samples were obtained at baseline and at 15-minute intervals post-treatment up to 90 minutes. RESULTS: ING increased total REE (INP 61.5 ± 1.2 kcal vs ING 69.4 ± 1.2 kcal; P = 0.027). There were no between-treatment differences in blood glucose, food intake and appetite. There were no adverse effects. CONCLUSION: ING acutely increases REE without increasing plasma glucose. Longer term studies with multiple daily dosing will establish whether this affects body weight.

Effects of combined GIP and GLP-1 infusion on energy intake, appetite and energy expenditure in overweight/obese individuals: a randomised, crossover study.

AIMS/HYPOTHESIS: Glucagon-like peptide 1 (GLP-1) reduces appetite and energy intake in humans, whereas the other incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), seems to have no effect on eating behaviour. Interestingly, studies in rodents have shown that concomitant activation of GIP and GLP-1 receptors may potentiate the satiety-promoting effect of GLP-1, and a novel dual GLP-1/GIP receptor agonist was recently shown to trigger greater weight losses compared with a GLP-1 receptor agonist in individuals with type 2 diabetes. The aim of this study was to delineate the effects of combined GIP and GLP-1 receptor activation on energy intake, appetite and resting energy expenditure in humans. METHODS: We examined 17 overweight/obese men in a crossover design with 5 study days. On day 1, a 50 g OGTT was performed; on the following 4 study days, the men received an isoglycaemic i.v. glucose infusion (IIGI) plus saline (154 mmol/l NaCl; placebo), GIP (4 pmol kg-1 min-1), GLP-1 (1 pmol kg-1 min-1) or GIP+GLP-1 (4 and 1 pmol kg-1 min-1, respectively). All IIGIs were performed in a randomised order blinded for the participant and the investigators. The primary endpoint was energy intake as measured by an ad libitum meal after 240 min. Secondary endpoints included appetite ratings and resting energy expenditure, as well as insulin, C-peptide and glucagon responses. RESULTS: Energy intake was significantly reduced during IIGI+GLP-1 compared with IIGI+saline infusion (2715 ± 409 vs 4483 ± 568 kJ [mean ± SEM, n = 17], p = 0.014), whereas there were no significant differences in energy intake during IIGI+GIP (4062 ± 520 kJ) or IIGI+GIP+GLP-1 (3875 ± 451 kJ) infusion compared with IIGI+saline (p = 0.590 and p = 0.364, respectively). Energy intake was higher during IIGI+GIP+GLP-1 compared with IIGI+GLP-1 infusion (p = 0.039). CONCLUSIONS/INTERPRETATION: While GLP-1 infusion lowered energy intake in overweight/obese men, simultaneous GIP infusion did not potentiate this GLP-1-mediated effect. TRIAL REGISTRATION: ClinicalTrials.gov NCT02598791 FUNDING: This study was supported by grants from the Innovation Fund Denmark and the Vissing Foundation.

Switching from sitagliptin to liraglutide to manage patients with type 2 diabetes in the UK: A long-term cost-effectiveness analysis.

AIMS: The recent LIRA-SWITCH trial showed that switching from sitagliptin 100 mg to liraglutide 1.8 mg led to statistically significant and clinically relevant improvements in glycated haemoglobin (HbA1C) and body mass index (BMI). Based on these findings, the aim of the present study was to assess the long-term cost-effectiveness of switching from sitagliptin to liraglutide in patients with type 2 diabetes in the UK. MATERIALS AND METHODS: The IQVIA CORE Diabetes Model Version 8.5+ was used to project costs and clinical outcomes over patients' lifetimes. Baseline cohort characteristics and treatment effects were derived from the LIRA-SWITCH trial. Future costs and clinical benefits were discounted at 3.5% annually. Costs were accounted in pounds sterling (GBP) and expressed in 2016 values. One-way and probabilistic sensitivity analyses were performed. RESULTS: Model projections showed improved quality-adjusted life expectancy for patients with poorly controlled HbA1c upon switching from sitagliptin to liraglutide, compared with continuing sitagliptin treatment (9.18 vs 9.02 quality-adjusted life years [QALYs]). Treatment switching was associated with increased overall costs (GBP 24737 vs GBP 22362). Higher pharmacy costs were partially offset by reduced diabetes-related complication costs in patients who switched to liraglutide. Switching to liraglutide was associated with an incremental cost-effectiveness ratio of GBP 15423 per QALY gained vs continuing with sitagliptin treatment. CONCLUSIONS: Switching from sitagliptin 100 mg to liraglutide 1.8 mg in patients with poor glycaemic control was projected to improve clinical outcomes and is likely to be considered cost-effective in the UK setting and, therefore, a good use of limited NHS resources.

Efectividad y seguridad de la asociación naltrexona/bupropión para el tratamiento de sobrepeso y obesidad / Effectiveness and safety of the naltrexone / bupropion association for treatment of overweight and obesity

INTRODUCCIÓN: La obesidad es una enfermedad crónica metabólica caracterizada por um aumento de la grasa corporal cuya magnitud y distribución condiciona las comorbilidades y la salud del individuo. Su incidencia muestra un aumento sostenido en todo el mundo, tanto en adultos como en niños y adolescentes. El sobrepeso y la obesidad se encuentran actualmente entre los principales factores de riesgo de muerte y de carga de enfermedad a nivel mundial. La obesidad representa un importante factor de riesgo para el desarrollo de enfermedades crónicas de gran prevalencia en países desarrollados y en vías de desarrollo, como la Hipertensión arterial (HTA), dislipemia, diabetes mellitus tipo 2, cardiopatía isquémica, accidente vascular cerebral, síndrome de hipoventilación y apnea del sueño, y otras. La pérdida de peso intencional se asocia a una reducción de los riesgos metabólicos mencionados. En la Argentina se estimó que, si la prevalencia de sobrepeso y obesidad se hubiera mantenido en valores como los observados en 2005; en el año 2013 se hubieran evitado el 5,5% de las muertes ocorridas en adultos, que representan cerca de 18.000 fallecimientos. Según datos de um estudio publicado en 2010, el excesso de peso en nuestro país implicó durante ese año una pérdida de 596.704 años de vida saludables. CARACTERÍSTICAS DE LA TECNOLOGÍA: Descripción: La naltrexona es un antagonista competitivo de los receptores opioides m (mu), k (kappa) y d (delta). El bupropion es un inhibidor de la recaptación de dopamina y norepinefrina. Estudios preclínicos sugirieron que los dos fármacos de esta asociación pueden actuar en dos áreas cerebrales diferentes, involucradas en la regulación de la ingesta calórica: el hipotálamo (centro regulador del apetito), y el circuito dopaminérgico mesolímbico (sistema de recompensa). Se postula que estos dos componentes presentan una acción sinérgica para la reducción de la ingesta de alimentos (asociación naltrexona/bupropion= NB32) (16). ESTRATEGIA DE BÚSQUEDA: Se realizó una búsqueda bibliográfica llevada a cabo por dos investigadores de manera independiente en los siguientes sitios de búsqueda: Medline/Pubmed, Epistemonikos, TripDataBase, Cochrane Library y Clinical Trials.gov. También se buscaron recomendaciones y políticas de aprobación en FDA, EMA, CRD York. Las palabras clave utilizadas fueron: obesity, naltrexone, bupropion. Las estrategias de búsqueda completas y los artículos encontrados y selecionados se encuentran en el anexo N°2. RESULTADOS: Los resultados en salud considerados fueron: eventos adversos cardiovasculares severos, porcentaje de pacientes que descendieron 5% del peso corporal, porcentaje de pacientes que descendieron 10% del peso corporal, reducción de la circunferencia de cintura, variaciones em determinados parámetros metabólicos de riesgo, calidad de vida asociada a la obesidad, eventos adversos psiquiátricos y discontinuación del tratamento debido a efectos colaterales. El análisis de la evidencia recuperada tuvo como resultados, para los puntos finales de Efectividad, diferencias significativas desde el punto de vista estadístico en favor de la asociación NB, en cuanto a los desenlaces: Descenso del 5% de peso, Descenso del 10% de peso y Circunferencia abdominal. La magnitud de la diferencia en estos casos fue relevante desde el punto de vista clínico. La magnitud de la diferencia de los siguientes resultados no fue considerada relevante desde el punto de vista clínico: Reducción del nivel de triglicéridos plasmáticos y Glucemia en ayunas. Por otro lado el análisis mostró que para los desenlaces Presión Arterial Sistólica y Presión Arterial Diastólica la diferencia en la reducción de los valores fue estadísticamente significativa en favor de los grupos que recibieron placebo, pero su magnitud que no fue considerada clínicamente significativa por los expertos temáticos. CONCLUSIONES: La evidencia disponible sobre la efectividad de esta asociación farmacológica para el manejo de una patología crónica como es la obesidad, es muy limitada para los puntos finales duros, que tienen real impacto en la salud de los pacientes. En cuanto a los desenlaces intermedios, aunque significativos, la duración acotada de los estudios no permite inferir la permanencia de sus beneficios a largo plazo. Esto último es muy importante dado que la tendência a la pérdida de efectividad a largo plazo de las intervenciones para el manejo de esta condición es habitual. En cuanto a la seguridad, se carece de datos sobre los puntos finales más relevantes como son los eventos adversos cardiovasculares mayores, mientras que en el caso de los eventos adversos psiquiátricos los resultados son inconsistentes en el cuerpo de la evidencia.

Effects of PYY3-36 and GLP-1 on energy intake, energy expenditure, and appetite in overweight men.

Our aim was to examine the effects of GLP-1 and PYY3-36, separately and in combination, on energy intake, energy expenditure, appetite sensations, glucose and fat metabolism, ghrelin, and vital signs in healthy overweight men. Twenty-five healthy male subjects participated in this randomized, double-blinded, placebo-controlled, four-arm crossover study (BMI 29 ± 3 kg/m(2), age 33 ± 9 yr). On separate days they received a 150-min intravenous infusion of 1) 0.8 pmol·kg(-1)·min(-1) PYY3-36, 2) 1.0 pmol·kg(-1)·min(-1) GLP-1, 3) GLP-1 + PYY3-36, or 4) placebo. Ad libitum energy intake was assessed during the final 30 min. Measurements of appetite sensations, energy expenditure and fat oxidation, vital signs, and blood variables were collected throughout the infusion period. No effect on energy intake was found after monoinfusions of PYY3-36 (-4.2 ± 4.8%, P = 0.8) or GLP-1 (-3.0 ± 4.5%, P = 0.9). However, the coinfusion reduced energy intake compared with placebo (-30.4 ± 6.5%, P < 0.0001) and more than the sum of the monoinfusions (P < 0.001), demonstrating a synergistic effect. Coinfusion slightly increased sensation of nausea (P < 0.05), but this effect could not explain the effect on energy intake. A decrease in plasma ghrelin was found after all treatments compared with placebo (all P < 0.05); however, infusions of GLP-1 + PYY3-36 resulted in an additional decrease compared with the monoinfusions (both P < 0.01). We conclude that coinfusion of GLP-1 and PYY3-36 exerted a synergistic effect on energy intake. The satiating effect of the meal was enhanced by GLP-1 and PYY3-36 in combination compared with placebo. Coinfusion was accompanied by slightly increased nausea and a decrease in plasma ghrelin, but neither of these factors could explain the reduction in energy intake.

Improving diet and physical activity to reduce population prevalence of overweight and obesity: an overview of current evidence.

OBJECTIVE: The aim of this study is to provide an overview of interventions to reduce or prevent overweight or obesity and improve diet or physical activity. METHODS: A review of meta-analyses and/or systematic reviews of these interventions in any setting or age group were conducted. Narrative systematic reviews were included for intervention categories with limited meta-analyses available. Summary measures including weighted mean difference, standardised mean difference, and I-squared, were examined. RESULTS: A total of 60 meta-analyses and 23 systematic reviews met the inclusion criteria. Dietary interventions and multi-component interventions targeting overweight and obesity appeared to have the greatest effects, particularly in comparison with workplace or technology or internet-based interventions. Pharmaceutical and surgical interventions produced favourable results for specific population sub-groups (i.e. morbidly obese). Population-wide strategies such as policy interventions have not been widely analysed. The effectiveness of the interventions to assist in maintaining behaviour or weight change remains unclear. CONCLUSIONS: Various individually targeted interventions were shown to reduce body weight, although effect sizes were typically modest, and the durability of effects has been questioned. New approaches to evaluating population-based interventions, such as taxes and regulation, are recommended. Future research modelling the long-term effects of interventions across the lifespan would also be beneficial.

Impact of BMI and BMI change on future drug expenditures in adults: results from the MONICA/KORA cohort study.

BACKGROUND: The evidence on the long-term economic effects of obesity is still scarce. This study aims to analyse the impact of body mass index (BMI) and BMI-change on future pharmaceutical utilisation and expenditures. METHODS: Based on data from 2,946 participants in a German population-based health survey (MONICA/KORA, 1994/95) and the follow-up study (2004/05), drug intake and expenditures were estimated using a bottom-up approach. Using univariate and multivariate methods, we analysed the impact of baseline BMI and BMI-change on drug utilisation and expenditures after 10 years. RESULTS: The use of pharmaceuticals was more likely in moderately and severely obese compared to the normal weight group (OR 1.8 and 4.0, respectively). In those who reported pharmaceutical intake, expenditures were about 40% higher for the obese groups. A 1-point BMI-gain in 10 years was, on average, associated with almost 6% higher expenditures compared to a constant BMI. CONCLUSION: The results suggest that obesity as well as BMI-gain are strong predictors of future drug utilisation and associated expenditures in adults, and thus highlight the necessity of timely and effective intervention and prevention programmes. This study complements the existing literature and provides important information on the relevance of obesity as a health problem.

Lycium barbarum increases caloric expenditure and decreases waist circumference in healthy overweight men and women: pilot study.

BACKGROUND: Lycium barbarum (L. barbarum), a traditional Asian medicinal therapy for diabetes and other conditions, has been shown to increase metabolic rate and to reduce body-weight gains in rodent models, as well as to produce clinical improvements in general feelings of well-being including energy level. OBJECTIVE: To investigate the impact of L. barbarum consumption on (1) caloric expenditure and (2) changes in morphometric parameters (waist circumference) in healthy human adults. METHOD: Two separate randomized, double-blind, placebo-controlled, small clinical studies were conducted using a standardized L. barbarum fruit juice, GoChi, and assessing its effects on (1) resting metabolic rate (RMR) and postprandial energy expenditure (PPEE) as measured by indirect calorimetry after single-bolus intake of 3 doses of L. barbarum (30, 60, and 120 ml) and placebo; and (2) waist circumference and other morphometric changes in a 14-day intervention trial (120-ml daily intake) in the subjects (age = 34 years, body mass index = 29 kg/m(2)). RESULTS: (1) A single bolus of L. barbarum intake increased PPEE 1 through 4 hours postintake over the baseline level in a dose-dependent manner and was significantly higher than the placebo group by 10% at 1 hour postintake of 120 ml (p < 0.05). (2) In a 14-day intervention trial, L. barbarum was found to significantly decrease waist circumference by 5.5 ± 0.8 cm (n = 15) compared with the preintervention measurements and placebo group at postintervention day 15 (p < 0.01). By contrast, the changes in the placebo group (n = 14) from preinterventions was 0.9 ± 0.8 cm, which was not statistically significant. CONCLUSIONS: These results show that L. barbarum consumption increases metabolic rate and reduces the waist circumference, relative to placebo treated control subjects.

Lorcaserin, a 5-HT(2C) receptor agonist, reduces body weight by decreasing energy intake without influencing energy expenditure.

CONTEXT: Lorcaserin, a selective 5-hydroxytryptamine (5-HT)(2C) receptor agonist, reduces body weight. It is unclear whether weight loss is due to reduced energy intake (EI) or also to enhanced energy expenditure (EE). OBJECTIVE: This study tested the effect of lorcaserin on EI and EE. DESIGN, PARTICIPANTS, AND INTERVENTION: In a double-blind, randomized, placebo-controlled trial, 57 (39 women) overweight and obese (body mass index, 27-45 kg/m(2)) adults were randomized to placebo (n = 28) or 10 mg twice daily lorcaserin (n = 29) for 56 d. Weight maintenance was imposed during d 1-7. Beginning on d 8, participants followed a diet and exercise plan targeting a 600 kcal/d deficit. OUTCOMES: At baseline and after 7 and 56 d of treatment, we measured body weight, body composition (dual x-ray absorptiometry), blood pressure, heart rate, EI at lunch and dinner, subjective appetite ratings, and 24-h EE and 24-h-respiratory quotient (RQ), measured by indirect calorimetry in a respiratory chamber. RESULTS: After 7 d of weight maintenance, EI was significantly (P < 0.01) reduced with lorcaserin but not placebo (mean ± sem for lorcaserin, -286 ± 86 kcal; placebo, -147 ± 89 kcal). After 56 d, lorcaserin resulted in significantly larger reductions in body weight (lorcaserin, -3.8 ± 0.4 kg; placebo, -2.2 ± 0.5 kg; P < 0.01), EI (lorcaserin, -470 ± 87 kcal; placebo, -205 ± 91 kcal; P < .05), and appetite ratings than in placebo. Changes in 24-h EE and 24-h RQ did not differ between groups, even after 24-h EE was adjusted for body weight and composition. Compared with placebo, lorcaserin had no effect on systolic or diastolic blood pressure or heart rate after 56 d. CONCLUSIONS: Lorcaserin reduces body weight through reduced EI, not altered EE or RQ.

Effect of the look AHEAD study intervention on medication use and related cost to treat cardiovascular disease risk factors in individuals with type 2 diabetes.

OBJECTIVE: To examine the effect of a lifestyle intervention to produce weight loss and increased physical fitness on use and cost of medications to treat cardiovascular disease (CVD) risk factors in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: Look AHEAD is a multicenter randomized controlled trial of 5,145 overweight or obese individuals with type 2 diabetes, aged 45-76 years. An intensive lifestyle intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education (DSE) condition. Medications prescribed to treat diabetes, hypertension, and hyperlipidemia were compared at baseline and 1 year. Medication costs were conservatively estimated using prices from a national online pharmacy. RESULTS: Participants randomized to an ILI had significantly greater improvements in CVD risk parameters and reduced medication use and cost compared with those assigned to DSE. At 1 year, average number of medications prescribed to treat CVD risk factors was 3.1 +/- 1.8 for the ILI group and 3.6 +/- 1.8 for the DSE group (P < 0.0001), with estimated total monthly medication costs of $143 and $173, respectively (P < 0.0001). DSE participants meeting optimal care goals at 1 year were taking an average of 3.8 +/- 1.6 medications at an estimated cost of $194/month. ILI participants at optimal care required fewer medications (3.2 +/- 1.7) at lower cost ($154/month) (P < 0.001). CONCLUSIONS: At 1 year, ILI significantly improved CVD risk factors, while at the same time reduced medication use and cost. Continued intervention and follow-up will determine whether these changes are maintained and reduce cardiovascular risk.