Trends in the use and cost of human and analogue insulins in a Colombian population, 2011-2015.

OBJECTIVES: Diabetes mellitus is a common disease among the general population and imposes considerable costs on health care systems. Insulin is used to treat type 1 diabetes mellitus and as an adjuvant to oral agents in advanced stages of type 2 diabetes mellitus. The objective was to describe the trends in use and cost of human and analogue insulins for Colombian patients. STUDY DESIGN: Descriptive retrospective analysis of prescriptions of human and analogue insulins on a monthly basis for the period from July 1, 2011 to February 2, 2015. METHODS: Information was collected for the database population of two insurance companies. Frequencies and proportions were calculated; estimated economic impact was expressed as net cost and cost per thousand inhabitants per day. RESULTS: During the observation period, there was continuous growth in use of insulin, mainly in analogue forms (34.0% growth). At the start of the study, 10.4% of subjects were using an analogue insulin; this figure was 62.6% at the end of the study. In 2012, the average cost per 1000 inhabitants/day was US$1.7 for analogue and US$0.8 for human insulins. At the end of the observation period these costs had risen to US$9.2 for analogue (441.1% increase) and fallen to US$0.5 for human insulin (58.3% decrease). CONCLUSIONS: There has been an increase in the unit cost and frequency of use of insulin analogues for anti-diabetic therapy in Colombian patients. Moreover, there is controversy over whether insulin analogues are a more cost-effective treatment than human insulins for the general diabetic population.

Pharmacological treatment and impairment of pulmonary function in patients with type 2 diabetes: a cross-sectional study.

INTRODUCTION: There is no clear relationship between type 2 diabetes mellitus and lung function decline; it is also unclear whether the type of treatment can modify spirometric variables and levels of inflammatory biomarkers.  OBJECTIVES: To compare pulmonary function in patients with type 2 diabetes treated with an insulin-sensitizing agent (metformin) and in those treated with secretagogues, as well as combined with insulin, and to evaluate differences in inflammatory biomarkers between treatment groups.  MATERIAL AND METHODS: We conducted a cross-sectional analytic study in 196 diabetic patients with type 2 diabetic mellitus. Spirometric variables and levels of inflammatory biomarkers (ferritin, fibrinogen, C-reactive protein, interleukin 6, tumor necrosis factor-alpha), were obtained. Residual values (observed minus expected) for forced vital capacity and for forced expiratory volume were calculated and compared between treatment types. Differences in median levels of biomarkers were also compared.  RESULTS: After adjustment by known determinants of lung function, and by the control and duration of type 2 diabetes, patients treated with the insulin-sensitizing agent had statistically significant lower differences against expected values for forced vital capacity compared with secretagogues (-212.1 ml vs 270.2 ml, p=0.039), as well as for forced expiratory volume, but without statistical significance (-133.2 mL vs -174.8 mL, p>0.05). In the group of patients treated with the insulin-sensitizing agent, ferritin and tumor necrosis factor-alpha levels were lower (p<0.01).  CONCLUSION: This study supports the hypothesis that insulin-sensitizing agents appear to be associated with less deterioration of lung function and less systemic inflammation in type 2 diabetes. The present study serves to formulate new hypothesis and research projects.

Use of cross-reactivity immunoassay to orient insulin replacement in diabetic patients with high levels of insulin antibodies.

The prevalence and high levels of anti-insulin antibodies (IA) have frequently been associated with brittle diabetes, lipodystrophy in the areas where the insulin is injected and/or poor metabolic control. When this happens the usual criterion adopted is the empirical change of insulin type and/or formulation intending to diminish the IA level and then to decrease the undesirable side-effects. Here, we present a rational two step radiometric method consisting in: A) a first-line radioligand binding assay (RBA) to assess IA in sera of these patients and detecting those with high levels. B) applying a displacement assay (RIA) to determine the in vitro cross-reactivity parameters (affinity constants and selectivity ratios) that quantify the relative degree of interaction between antibodies and alternative insulin analogs. From these results we conclude that conventional criteria for selection of insulin analogs, in terms of pharmacokinetic and pharmacodinamic parameters, should be complemented with an appropriate test to assess affinity parameters when high IA title is demonstrated. •This manuscript introduces a rational method to determine the appropriated insulin replacement when high insulin antibodies levels are present.•This protocol provides instructions and details in mathematical tools and laboratory processes for the analysis of serum samples.•This method proved to be successful in a single case and requires confirmation using a large group of patients.

Tratamiento farmacológico y deterioro de la función pulmonar en pacientes con diabetes de tipo 2: un estudio de corte transversal / Pharmacological treatment and impairment of pulmonary function in patients with type 2 diabetes: a cross-sectional study

Introducción. La relación de la diabetes mellitus de tipo 2 con el deterioro de la función pulmonar no es clara, como tampoco si el tipo de tratamiento modifica los parámetros espirométricos e inflamatorios. Objetivo. Comparar la función pulmonar de pacientes con diabetes mellitus de tipo 2 tratados con un agente de sensibilización a la insulina (metformina) y de los tratados con secretagogos, así como de estos combinados con insulinas, y evaluar las diferencias en los biomarcadores de inflamación de los grupos. Materiales y métodos. Se hizo un estudio analítico de corte transversal en 196 pacientes con diabetes mellitus de tipo 2. Se midieron las variables espirométricas y la concentración sanguínea de biomarcadores de inflamación (ferritina, fibrinógeno, proteína C reactiva, interleucina 6 y factor de necrosis tumoral alfa). Se analizaron los valores residuales (valores observados menos valores predichos) para la capacidad vital forzada y el volumen espiratorio forzado en los diferentes tipos de tratamiento. También, se compararon las diferencias en las medianas de las concentraciones de los biomarcadores, según los tipos de tratamiento. Resultados. Después de ajustar según los factores determinantes de la función pulmonar y el control y la duración de la diabetes mellitus de tipo 2, los valores esperados de la capacidad vital forzada de los pacientes tratados con agentes de sensibilización a la insulina fue menor que los de aquellos tratados con secretagogos (-212,1 ml Vs. -270,2 ml; p=0,039), y lo mismo se registró en el volumen espiratorio forzado durante el primer segundo (-133,2 ml Vs. -174,8 ml; p>0,05), aunque dichas diferencias no fueron estadísticamente significativas. En el grupo de pacientes tratados con agentes de sensibilización a la insulina, las concentraciones de ferritina y del factor de necrosis tumoral alfa fueron menores (p<0,01). Conclusión. Los resultados de este estudio respaldan la hipótesis de que los agentes de sensibilización a la insulina estarían asociados con un menor deterioro de la función pulmonar y una menor inflamación sistémica en los pacientes diabéticos. Asimismo, sirve como base para la formulación de nuevas hipótesis y trabajos de investigación.

Introduction: There is no clear relationship between type 2 diabetes mellitus and lung function decline; it is also unclear whether the type of treatment can modify spirometric variables and levels of inflammatory biomarkers. Objectives: To compare pulmonary function in patients with type 2 diabetes treated with an insulin-sensitizing agent (metformin) and in those treated with secretagogues, as well as combined with insulin, and to evaluate differences in inflammatory biomarkers between treatment groups. Materials and methods: We conducted a cross-sectional analytic study in 196 diabetic patients with type 2 diabetic mellitus. Spirometric variables and levels of inflammatory biomarkers (ferritin, fibrinogen, C-reactive protein, interleukin 6, tumor necrosis factor-alpha), were obtained. Residual values (observed minus expected) for forced vital capacity and for forced expiratory volume were calculated and compared between treatment types. Differences in median levels of biomarkers were also compared. Results: After adjustment by known determinants of lung function, and by the control and duration of type 2 diabetes, patients treated with the insulin-sensitizing agent had statistically significant lower differences against expected values for forced vital capacity compared with secretagogues (-212.1 ml vs 270.2 ml, p=0.039), as well as for forced expiratory volume , but without statistical significance (-133.2 mL vs -174.8 mL, p>0.05). In the group of patients treated with the insulin-sensitizing agent, ferritin and tumor necrosis factor-alpha levels were lower (p<0.01). Conclusion: This study supports the hypothesis that insulin-sensitizing agents appear to be associated with less deterioration of lung function and less systemic inflammation in type 2 diabetes. The present study serves to formulate new hypothesis and research projects.

Insulinas análogas: responsabilidade do SUS e a judicialização / Analog Insulins: SUS liability and the judicialization / Las insulinas similares: la responsabilidad del SUS y la judicialización

Trata-se de um estudo descritivo, epidemiológico e analítico com abordagem qualiquantitativa. O artigo buscou identificar a relação entre cobertura da Estratégia de Saúde da Família e o aumento de ações judiciais de insulinas análogas nas regiões Sul e Nordeste do Brasil. Nos anos 2010, 2011 e 2012, o consumo de insulinas análogas foi crescente tanto na região sul quanto nordeste. A região sul, apesar de ter um SUS organizado, IDH desenvolvido e educação estruturada, apresentou falhas no programa de diabetes. Em contrapartida, a região nordeste possui IDH baixo na maioria dos municípios e educação deficiente, porém, observou-se a necessidade de reorganização dos programas voltados ao atendimento de usuários portadores de doenças crônicas, em especial, a diabetes, nessa região. Entende-se, que o fortalecimento da atenção básica como porta de entrada para o SUS, nas regiões estudadas pode minimizar o problema da judicialização da saúde.

This is a descriptive, epidemiological and analytical approach study, within a qualitative-quantitative perspective. The article sought to identify the relationship between coverage of the Family Health Strategy and the increase in lawsuits related to analog insulin in the South and Northeast regions of Brazil. In the years 2010, 2011 and 2012, analog insulins consumption grew over the years in the South as in the Northeast. The Southern region, despite having an organized SUS, high HDI and a wellstructured education, had flaws in the national diabetes program. In contrast, the Northeast region has a low HDI in most municipalities and poor education; however, there is a need for the reorganization of programs aimed at users with chronic diseases, especially diabetes in this region. It is understood that the strengthening of primary health care as a gateway to the Unified Health System in the studied regions can minimize the problem of judicialization in healthcare.

Se trata de un estudio descriptivo, epidemiológico y analítico con enfoque cuali- cuantitativa. El trabajo tiene como objetivo identificar la relación entre la estrategia de salud para la cobertura de la familia y el aumento de las demandas de las insulinas análogas en el sur y noreste de Brasil. En los años 2010, 2011 y 2012, el consumo de los análogos ha ido creciendo tanto en el sur como al noreste. La región del sur, a pesar de tener un sistema de salud organizad, Indice de Desarrollo Humano (IDH) desarrollado y estructurado de educación, presentó fallas en el programa de la diabetes. Por el contrario, la región noreste tiene un bajo IDH en la mayoría de los municipios y la educación deficiente. Sin embargo, no había la necesidad de reorganización de los programas destinados a los portadores de enfermedades crónicas, especialmente diabetes en esta región. Se entiende que el fortalecimiento de la atención primaria como puerta de entrada para el sistema público de salud, las regiones pueden minimizar el problema de la judicialización de la salud.

Insulin analogues versus human insulin in type 1 diabetes: direct and indirect meta-analyses of efficacy and safety

All patients with Diabetes Mellitus (DM) receive insulin therapy. In this study, we evaluated the efficacy, safety and tolerability of human insulin and insulin analogues. We performed a systematic review of the literature and a meta-analysis according to the Cochrane Collaboration methodology. In the absence of clinical studies comparing insulins, we performed a mixed treatment comparison to establish the differences between the active treatments. We included studies published from 1995 to 2010. HbA1c results, episodes of hypoglycemia and nocturnal hypoglycemia data were extracted and analyzed. Thirty-five randomized clinical trials were selected after examining the abstract and a full text review. These studies included 4,206 patients who received long-acting insulin analogues and 5,733 patients who received short-acting insulin analogues. Pooled data regarding efficacy indicated no significant differences in HbA1c values between glargine or detemir (once daily) and NPH insulin. However, a twice-daily dose of detemir produced differences in HbA1c values that favored detemir (-0.14% [95% CI: -0.21 to -0.08]; p<0.0001; I²=0%). Direct and indirect comparisons are consistent and show that there were no significant differences between human insulin and insulin analogues in efficacy or safety. Our results indicate that long- and short-acting insulin analogues offer few clinical advantages over conventional human insulin.

Todos os pacientes com Diabetes Mellitus (DM) tipo 1 recebem insulina. Neste estudo, avaliaram-se eficácia, segurança e tolerabilidade de insulinas humanas e análogas. Realizou-se uma revisão sistemática e meta-análise, de acordo com o preconizado pela Colaboração Cochrane. Na ausência de estudos clínicos comparando insulinas entre si, realizaram-se meta-análises de comparações indiretas a fim de estabelecer diferenças entre tratamentos ativos. Incluíram-se estudos de 1995 a 2010. Resultados de HbA1c, episódios de hipoglicemia e hipoglicemia noturna foram extraídos e analisados. Após leitura de resumos e, posteriormente, de artigos na íntegra, selecionaram-se 35 ensaios clínicos randomizados, totalizando 4206 pacientes utilizando insulina análoga de longa duração e 5733 pacientes insulina análoga de curta duração. Os resultados não demonstraram diferença estatisticamente significativa para redução de HbA1c entre glargina e detemir (uma vez ao dia) comparados a NPH. No entanto, insulina detemir utilizada duas vezes ao dia reduz a HbA1c (-0.14% [95% CI: -0.21 to -0.08]; p<0.0001; I²=0%). Comparações diretas e indiretas indicam que não existem diferenças significativas na médica de redução de HbA1c, independente da posologia de detemir, sendo estes resultados de eficácia e segurança consistentes. Os resultados indicam que insulinas análogas de longa ou curta duração apresentam pequenas vantagens, quando comparadas às insulinas tradicionais. Ademais, não existem diferenças entre eficácia e segurança quando comparamos insulinas análogas entre si.