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.

Por que as pessoas recorrem ao Judiciário para obter o acesso aos medicamentos? O caso das insulinas análogas na Bahia / Why do people appeal to the courts for access to medication? The case of insulin analogues in Bahia (Brazil)

Resumo As insulinas análogas são alvo de controvérsias quanto à sua superioridade terapêutica em relação às humanas. Talvez, em parte, devido a isso, são objetos frequentes de ações judicias. A judicialização da saúde tem sido muito estudada, mas pouco se sabe sobre os motivos que levam as pessoas a recorrerem ao Judiciário para obter acesso a medicamentos no SUS. Sendo assim, o presente estudo tem por objetivo analisar os motivos que levaram as pessoas a recorrerem ao Judiciário para obter o acesso às insulinas análogas no estado da Bahia, tratando-se de um estudo de caso apoiado em fonte documental. Foram analisadas, entre 2010 e 2013, 149 ações judiciais que solicitaram o fornecimento de análogas pela secretaria estadual da saúde. Os motivos do recurso à Justiça, citados nos autos, podem ser classificados em: hipossuficiência financeira do usuário, necessidade de insulina análoga, dever e obrigação do Estado em fornecê-las e dificuldades burocráticas. Majoritariamente, as pessoas recorreram ao Judiciário, porque os médicos que as acompanham, divergindo das políticas oficiais, acreditam que as insulinas análogas são melhores do que às humanas e o sistema público de saúde não as dispensa, não dispondo elas de condições financeiras que lhes permitam adquiri-las com recursos próprios.

Abstract Insulin analogues have been the object of controversy concerning their therapeutic superiority to human insulin. Perhaps, in part, because of this, insulin analogues are frequently the subject of lawsuits. The judicialization of health has been well studied, but little is known about the reasons that lead people to go to the courts to obtain access to medicines on SUS (the Brazilian National Health System). Therefore, this study aims to analyze the reasons that led people to appeal to the courts to obtain access to insulins analogues in the state of Bahia. This is a case study based on documentary sources. Between 2010 and 2013, 149 lawsuits requiring insulin analogues from the state health authority were filed in the courts. The main reasons for the appeal to the courts, cited in the cases, can be grouped into four categories: the users’ lack of finances, an essential need for insulin analogue, the duty and obligation of the state to provide them and bureaucratic difficulties. People turned to the courts, mostly, because doctors who accompany their patients have shifted from the official policy, believing that insulin analogues are better than human insulins. They also recognize that the public health system does not distribute them nor does it give doctors the wherewithal to purchase them with their own resources.

Comparative study between two recombinant human NPH insulin formulations for the treatment of type 2 diabetes mellitus

ABSTRACT Objective To compare the effects of the neutral protamine Hagedorn (NPH) recombinant human insulin formulations Gansulin and Humulin N® on the glycemic control of patients with type 2 diabetes mellitus (T2DM). Subjects and methods Prospective, double-blind, randomized, parallel, single-center study of 37 individuals with T2DM treated with NPH insulin formulations. The Tukey-Kramer test for multiple comparisons, the Wilcoxon paired comparison test and the Chi-Square test were used for the statistical analyses. The significance level was set at 5% (p < 0.05). Results The NPH insulin formulations Humulin and Gansulin similarly reduced the HbA1c levels observed at the end of the study compared with the values obtained at the beginning of the study. In the Humulin group, the initial HbA1c value of 7.91% was reduced to 6.56% (p < 0.001), whereas in the Gansulin group, the reduction was from 8.18% to 6.65% (p < 0.001). At the end of the study, there was no significant difference between the levels of glycated hemoglobin (p = 0.2410), fasting plasma glucose (FG; p = 0.9257) and bedtime plasma glucose (BG; p = 0.3906) between the two insulin formulations. There was no nt difference in the number of hypoglycemic events between the two insulin formulations, and no severe hyp episodes were recorded. Conclusion This study demonstrated similar glycemic control by NPH insulin Gansulin compared with human insulin Humulin N® in patients with T2DM.

BAY 41-2272 activates host defence against local and disseminated Candida albicans infections

In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation. .

Custo-efetividade e impacto orçamentário da saxagliptina como terapia adicional à metformina para o tratamento do diabetes mellitus tipo 2 no sistema de saúde suplementar do Brasil / Cost-effectiveness and budget impact of saxagliptine as additional therapy to metformin for the treatment of diabetes mellitus type 2 in the brazilian private health system

OBJETIVOS: Comparar custos e benefícios clínicos de três terapias adicionais à metformina (MF) para pacientes com diabetes mellitus tipo 2 (DMT2). MÉTODOS: Um modelo de simulação de eventos discretos foi construído para estimar a relação custo-utilidade (custo por QALY) da saxagliptina como uma terapia adicional à MF comparada à rosiglitazona ou pioglitazona. Um modelo de impacto orçamentário (BIM - Budget Impact Model) foi construído para simular o impacto econômico da adoção de saxagliptina no contexto do Sistema Suplementar de Saúde brasileiro. RESULTADOS: O custo de aquisição da medicação para o grupo de pacientes hipotéticos analisados, para o horizonte temporal de três anos, foi de R$ 10.850.185,00, R$ 14.836.265,00 e R$ 14.679.099,00 para saxagliptina, pioglitazona e rosiglitazona, respectivamente. Saxagliptina exibiu menores custos e maior efetividade em ambas as comparações, com economias projetadas para os três primeiros anos de -R$ 3.874,00 e -R$ 3.996,00, respectivamente. O BIM estimou uma economia cumulativa de R$ 417.958,00 com o reembolso da saxagliptina em três anos a partir da perspectiva de uma operadora de plano de saúde com 1 milhão de vidas cobertas. CONCLUSÃO: Da perspectiva da fonte pagadora privada, a projeção é de que o acréscimo de saxagliptina à MF poupe custos quando comparado ao acréscimo de rosiglitazona ou pioglitazona em pacientes com DMT2 que não atingiram a meta de hemoglobina glicada (HbA1c) com metformina em monoterapia. O BIM, para a inclusão de saxagliptina nas listas de reembolso das operadoras de planos de saúde, indicou uma economia significativa para o horizonte de 3 anos.

OBJECTIVES: To compare costs and clinical benefits of three additional therapies to metformin (MF) for patients with diabetes mellitus type 2 (DM2). METHODS: A discrete event simulation model was built to estimate the cost-utility ratio (cost per quality-adjusted life years [QALY]) of saxagliptine as an additional therapy to MF when compared to rosiglitazone or pioglitazone. A budget impact model (BIM) was built to simulate the economic impact of saxagliptine use in the context of the Brazilian private health system. RESULTS: The acquiring medication costs for the hypothetical patient group analyzed in a time frame of three years, were R$ 10,850,185, R$ 14,836,265 and R$ 14,679,099 for saxagliptine, pioglitazone and rosiglitazone, respectively. Saxagliptine showed lower costs and greater effectiveness in both comparisons, with projected savings for the first three years of R$ 3,874 and R$ 3,996, respectively. The BIM estimated cumulative savings of R$ 417,958 with the repayment of saxagliptine in three years from the perspective of a health plan with 1,000,000 covered individuals. CONCLUSION: From the perspective of private paying source, the projection is that adding saxagliptine with MF save costs when compared with the addition of rosiglitazone or pioglitazone in patients with DM2 that have not reached the HbA1c goal with metformin monotherapy. The BIM of including saxagliptine in the reimbursement lists of health plans indicated significant savings on the three-year horizon.

Evaluación de políticas públicas de provisión de fármacos para diabetes mellitus tipo 2 en Argentina: estudio de caso / Evaluation of public drug provision policies for type 2 diabetes mellitus in Argentina: a case study

En Argentina, la provisión de fármacos para pacientes con diabetes mellitus tipo 2 (DM2) sin cobertura de salud se efectúa mediante programas públicos. En la provincia de Buenos Aires coexisten el programa Remediar, de nivel nacional, y el Programa de Prevención, Diagnóstico y Tratamiento del Paciente Diabético (PRODIABA), de nivel provincial. El presente trabajo estima el porcentaje de población adulta con DM2 sin cobertura del municipio de Bahía Blanca (provincia de Buenos Aires) con necesidad de tratamientos de antidiabéticos orales, que satisface su demanda en el sector público. Es un estudio cuantitativo que evalúa la demanda y la necesidad de provisión pública. Los resultados indican que: 1) el mayor porcentaje de la demanda se satisface en el primer nivel de atención; 2) la provincia de Buenos Aires financia el mayor porcentaje de comprimidos, seguida por el nivel municipal y el nacional; 3) el nivel local también interviene para satisfacer la demanda y 4) la provisión pública total solo daría cobertura a aproximadamente el 25% de las necesidades en el escenario correspondiente al consumo medio. Esto muestra que, incluso con diferentes programas públicos, la provisión no es suficiente y se requiere de la intervención local aun cuando la descentralización en la adquisición de fármacos no es recomendada por la teoría económica.

In Argentina, the provision of drugs for patients suffering from type 2 diabetes mellitus who lack health insurance is carried out through public programs. In the Province of Buenos Aires, the national program Remediar and the provincial program PRODIABA (from the Spanish Programa de Prevención, Diagnóstico y Tratamiento del Paciente Diabético) coexist. This study estimates the percentage of adults in the municipality of Bahia Blanca (Province of Buenos Aires) who suffer from type 2 diabetes mellitus and lack health insurance, thus satisfying their need for oral antidiabetic treatments within the public sector. It is a quantitative study that assesses the need and demand for public provision. The results indicate that: 1) the greatest percentage of demand is satisfied at the primary health care level; 2) the province of Buenos Aires funds the largest share of the pills, followed by the municipal and the national levels; 3) the local government intervenes to satisfy the demand and 4) the total public provision covers approximately 25% of the overall need in relation to the average consumption. This shows that despite the presence of these public programs, the provision is insufficient and thus requires the intervention of the local government even though economic theory does not recommend the decentralization of drug purchases.

Economic evaluation of outpatients with type 2 diabetes mellitus assisted by a pharmaceutical care service / Avaliação econômica de pacientes ambulatoriais portadores de diabetes melito tipo 2 assistidos por um serviço de atenção farmacêutica

OBJECTIVE: To analyze the costs related to visits and drug prescription in outpatients with type 2 diabetes mellitus assisted by a pharmaceutical care service. SUBJECTS AND METHODS: A prospective and experimental study was carried out. Seventy one patients were divided into two groups: control and pharmaceutical care. Patients in the pharmaceutical care group were followed up monthly by a single clinical pharmacist. RESULTS: The pharmaceutical care group had a statistically significant reduction in costs of metformin and emergency department visits, and increased costs with their family physicians. On the other hand, the control group had a statistically significant increase of 21.3 percent in the general costs of treatment and visits. CONCLUSION: The pharmaceutical care group maintained the same costs related to drugs and visits, while the control group showed a significant increase in general costs.

OBJETIVO: Analisar os custos relacionados a medicamentos e consultas em pacientes portadores de diabetes melito tipo 2 acompanhados por um programa de atenção farmacêutica. SUJEITOS E MÉTODOS: Estudo prospectivo e experimental foi realizado em 71 pacientes, os quais foram divididos em dois grupos: atenção farmacêutica e controle. Os pacientes do grupo atenção farmacêutica foram acompanhados mensalmente por um farmacêutico clínico. RESULTADOS: O grupo atenção farmacêutica apresentou redução estatisticamente significativa no custo da metformina e nas visitas de pronto atendimento e aumento no custo das consultas de atenção primária. Por outro lado, o grupo controle apresentou elevação estatisticamente significativa nos custos gerais de tratamento farmacológico e nas consultas em geral na ordem de 21,3 por cento. CONCLUSÃO: O grupo atenção farmacêutica apresentou manutenção dos custos relacionados a consultas e medicamentos, enquanto o grupo controle apresentou aumento destes.

Preços e disponibilidade de medicamentos no Programa Farmácia Popular do Brasil / Precios y disponibilidad de medicamentos en el Programa Farmacia Popular de Brasil / Medicine prices and availability in the Brazilian Popular Pharmacy Program

OBJETIVO: Analisar o desempenho do Programa Farmácia Popular do Brasil perante os setores público e privado, em relação a: disponibilidade, preço e custo, para o paciente, de medicamentos para hipertensão e diabetes. MÉTODOS: Foi utilizada a metodologia desenvolvida pela Organização Mundial da Saúde em conjunto com a Ação Internacional para Saúde, para comparação de preços e disponibilidade de medicamentos. A pesquisa foi aplicada em maio de 2007, em estabelecimentos de diferentes setores [público, privado e as modalidades própria (FPB-P) e expansão (FPB-E) do Programa], em 30 municípios do Brasil. Os quatro medicamentos analisados foram: captopril 25mg e hidroclorotiazida 25mg, para hipertensão, e metformina 500mg e glibenclamida 5mg, para diabetes. RESULTADOS: O FPB-E apresentou maior disponibilidade de medicamentos e o setor público, a menor. Tanto no setor público quanto na FPB-P o percentual de disponibilidade de similares foi maior que o de genéricos...

OBJECTIVE: To analyze the performance of the Programa Farmácia Popular do Brasil (FPB - Brazilian Popular Pharmacy Program) in the public and private sectors, in terms of availability and cost of medicines for hypertension and diabetes. METHODS: The methodology developed by the World Health Organization, in partnership with the Health Action International, was used to compare medicines prices and availability. This study was performed in May 2007, in different sectors (public, private and the Program's government-managed [FPB-P] and private-sector-managed [FPB-E] categories), in 30 cities in Brazil. A total of four medicines were analyzed: captopril 25mg and hydrochlorothiazide 25mg for hypertension; and metformin 500mg and glibenclamide 5mg for diabetes. RESULTS: FPB-E showed greatest medicine availability, while the public sector the lowest. The percentage of availability of similar medicines was higher than that of generic medicines, both in the public sector and in the FPB-P...

OBJETIVO: Analizar el desempeño del Programa Farmacia Popular de Brasil frente a los sectores público y privado, con relación a: disponibilidad, precio y costo para el paciente, de medicamentos para hipertensión y diabetes. MÉTODOS: Fue utilizada la metodología desarrollada por la Organización Mundial de la Salud en conjunto con la Acción Internacional para Salud, para comparar los precios y la disponibilidad de medicamentos. La investigación fue aplicada en mayo de 2007, en establecimientos de diferentes sectores [público, privado y las modalidades propia (FPB-P) y expansión (FPB-E) del Programa], en 30 municipios de Brasil. Los cuatro medicamentos analizados fueron: captopril 25 mg e hidroclorotiazida 25 mg, para hipertensión, y metformina 500 mg y glibenclamida 5 mg, para diabetes. RESULTADOS: El FPB-E presentó mayor disponibilidad de medicamentos y el sector público, la menor. Tanto en el sector público como en la FPB-P el porcentaje de disponibilidad de similares fue mayor que el de los genéricos...

Measuring medicine prices in Peru: validation of key aspects of WHO/HAI survey methodology / Determinación de los precios de los medicamentos en Perú: validación de aspectos fundamentales del método de encuesta de la OMS/HAI

Objectives: To assess the possibility of bias due to the limited target list and geographic sampling of the World Health Organization (WHO)/Health Action International (HAI) Medicine Prices and Availability survey used in more than 70 rapid sample surveys since 2001. Methods: A survey was conducted in Peru in 2005 using an expanded sample of medicine outlets, including remote areas. Comprehensive data were gathered on medicines in three therapeutic classes to assess the adequacy of WHO/HAI's target medicines list and the focus on only two product versions. WHO/HAI median retail prices were compared with average wholesale prices from global pharmaceutical sales data supplier IMS Health. Results: No significant differences were found in overall availability or prices of target list medicines by retail location. The comprehensive survey of angiotensin-converting enzyme inhibitor, anti-diabetic, and anti-ulcer products revealed that some treatments not on the target list were costlier for patients and more likely to be unavailable, particularly in remote areas. WHO/HAI retail prices and IMS wholesale prices were strongly correlated for higher priced products, and weakly correlated for lower priced products (which had higher estimated retailer markups). Conclusions: The WHO/HAI survey approach strikes an appropriate balance between modest research costs and optimal information for policy. Focusing on commonly used medicines yields sufficient and valid results. Surveyors elsewhere should consider the limits of the survey data as well as any local circumstances, such as scarcity, that may call for extra field efforts.

Objetivos: Evaluar la posibilidad de sesgo debido a la limitación de la lista de referencia y del muestreo geográfico de la encuesta de precios y disponibilidad de medicamentos de la Organización Mundial de la Salud/Health Action International (OMS/HAI) usada en más de 70 muestras de encuestas rápidas desde el 2001. Métodos: En el año 2005, se realizó una encuesta en Perú, con una muestra ampliada de puntos de venta de medicamento, incluso en zonas remotas. Se recogieron datos integrales acerca de los medicamentos de tres clases terapéuticas, con el fin de evaluar la idoneidad de la lista de referencia de medicamentos de la OMS/HAI y el énfasis únicamente en dos versiones del producto. Las medianas de los precios al por menor de la OMS/HAI se compararon con el promedio de precios al por mayor del proveedor de datos mundiales de ventas farmacéuticas IMS Health. Resultados: No se observó ninguna diferencia significativa en la disponibilidad general ni en los precios de los medicamentos de la lista de referencia por localización de venta al por menor. La encuesta integral de los inhibidores de la enzima convertidora de la angiotensina, los antidiabéticos y los productos antiulcerosos reveló que algunos tratamientos que no están en la lista destinataria eran más caros para los pacientes y era más probable que no estuvieran a la venta, sobre todo en las regiones remotas. Los precios al por menor de la OMS/HAI y los precios al por mayor de IMS presentaron una correlación intensa en el caso de los productos de precio más alto, y la correlación fue débil en el caso de los productos de precio más bajo (que tuvieron márgenes de beneficio calculados más altos para el minorista). Conclusiones: El método de la encuesta de la OMS/HAI logra un equilibrio adecuado entre los costos de investigación moderados y la información óptima para la política. El énfasis en los medicamentos de uso frecuente produce unos resultados válidos y suficientes. Los encuestadores de otros...

Metabolic syndrome patient compliance with drug treatment

OBJECTIVES: 1) To evaluate the compliance with drug treatment in patients with metabolic syndrome. 2) To determine association between access to and use of medicines, as well as the level of knowledge of cardiovascular risk factors and compliance. INTRODUCTION: Low compliance has been one of the greatest challenges for the successful treatment of chronic diseases. Although this issue has been widely studied in patients with isolated hypertension, diabetes and dyslipidemia, compliance studies involving patients with these concomitant diseases or with metabolic syndrome diagnosis are scarce. METHODS: This was a cross-sectional study involving patients who have been diagnosed with metabolic syndrome according to the IDF criteria. Patients were being treated in a Health-Medical School Center bound to the Public Brazilian Healthcare System. This study was conducted in two phases. Phase I was characterized by analyzing medical records and Phase II involved interviewing the patients. A variation of the Morisky-Green Test was used to evaluate compliance. Compliance was the dependent variable and the independent variables included access to medicines, the use of medicines and the level of knowledge concerning cardiovascular risk factors. RESULTS: Two hundred and forty-three patients were identified as being eligible for Phase II, and 75 were included in the study. The average level of compliance was 5.44 points (standard deviation of 0.68), on a scale ranging from 1.00 to 6.00 points. There was no statistically meaningful association between independent variables and compliance. The level of patient knowledge of diet and dyslipidemia was considered to be low. CONCLUSIONS: Patients involved in this study exhibited a high level of compliance with drug treatment. Further research is needed to better elucidate the compliance behavior of patients who have been diagnosed with metabolic syndrome.

Nuevos retos del control de la hipertensión arterial en México / New challenges for the control of hypertension in México

Los nuevos lineamientos para el manejo de la hipertensión arterial plantean retos para nuestro sistema de salud. El primero referente a la cobertura del tratamiento hipertensivo, ya que sólo 21 por ciento recibe tratamiento antihipertensivo y de este porcentaje sólo 30 por ciento alcanza cifras < 140/90 mm Hg. El segundo consiste en mejorar las estrategias para su adecuada identificación, ya que existe un sobrediagnóstico que va de 16 a 26 por ciento. El tercero orientar el tratamiento a grupos de alto riesgo como los diabéticos y quienes ya presentaron alguna complicación cardiovascular, cuyas cifras de control deben ser < 130/85 mm Hg. El último reto es abatir el costo del tratamiento antihipertensivo. En el presente estudio se plantea resolver cada uno de estos retos y lograr la disminución de las complicaciones asociadas con la enfermedad