Basal insulin persistence in Brazilian participants with T2DM

SUMMARY OBJECTIVE Real-world effectiveness of basal insulin therapy is affected by poor treatment persistence, often occurring soon after initiation. This analysis is part of an international cross-sectional study conducted in T2DM patients and is intended to describe the reasons behind non-persistence to insulin therapy in Brasil. METHODS Responders to an online survey in seven countries were classified as continuers (no gap of ≥7 days), interrupters (interrupted therapy for ≥7 days within first 6 months, then restarted), and discontinuers (terminated therapy for ≥7 days within first 6 months, and did not start it again before the survey). We present the results from the Brazilian cohort. RESULTS Of 942 global respondents, 156 were from Brasil, with a mean age of 34 years and a mean of 5.8 years since T2DM diagnosis. Reasons contributing to insulin continuation (n=50) were improved glycemic control (82%) and improved physical feeling (50%). Common reasons for interruption (n=51) or discontinuation (n=55) were, respectively, weight gain (47.1%, 43.6%), hypoglycemia (45.1%, 38.2%), and pain from injections (39.2%, 49.1%). However, not all patients who reported weight gain and hypoglycemia as a reason for interruption or discontinuation experienced these: 16/24 (66.7%) and 22/24 (91.7%) participants had weight gain, and 13/23 (56.5%) and 15/21 (71.4%) had hypoglycemia, respectively. The most important reason for possible re-initiation for interrupters and discontinuers, respectively, was persuasion by the physician/HCP (80.4%, 72.7%). CONCLUSION The benefits of basal insulin therapy motivated continuers to persist with the treatment; experienced or anticipated side effects contributed to interruption and discontinuation. Physician and patient training is key in the treatment of diabetes.

RESUMO OBJETIVO Dados de vida real sobre como a eficácia da terapia com insulina é afetada pela baixa persistência ao tratamento que ocorre logo após o início da terapia. Esta análise é a parte brasileira de um estudo transversal internacional conduzido em pacientes com DM2 que teve como objetivo descrever as razões relacionadas à não persistência ao tratamento com insulina. METODOLOGIA O estudo realizado em sete países por meio de questionários on-line classificou como pacientes continuadores (aqueles que não apresentaram intervalo ≥7 dias sem uso da insulina), interrompedores (interromperam a terapia por ≥7 dias nos primeiros seis meses de uso, depois recomeçaram) e descontinuadores (interromperam a terapia por ≥7 dias nos primeiros seis meses de uso e não retornaram). Nesta análise descrevemos os dados da coorte brasileira. RESULTADOS Dos 942 pacientes incluídos, 156 eram do Brasil, com idade média de 34 anos e média de seis anos desde o diagnóstico de DM2. Razões que contribuíram para o uso contínuo da insulina (n=50) foram a melhora do controle glicêmico (82%) e a melhora no estado geral (50%). Razões para a interrupção (n=51) ou para a descontinuação (n=55) foram, respectivamente, ganho de peso (41,7%, 43,6%), hipoglicemia (45,1%, 38,2%) e dor à aplicação (39,2%, 49,1%). Entretanto, nem todos os pacientes que reportaram ganho de peso e hipoglicemia como possível razão para interrupção ou descontinuação realmente apresentaram esses eventos: 16/24 (66,7%) e 22/24 (91,4%) dos participantes apresentaram ganho de peso e 13/23 (56,6%) e 15/21 (71,4%) apresentaram hipoglicemia, respectivamente. A razão mais importante para o possível recomeço entre os interrompedores e descontinuadores foi a persuasão de médicos/profissionais de saúde (80,4% e 72,7%, respectivamente). CONCLUSÕES Os benefícios do tratamento com insulina basal motivaram continuadores a persistir com a terapia; a experiência ou a antecipação de eventos adversos contribuíram para a interrupção e descontinuação. O treinamento de médicos e pacientes é um dos pilares fundamentais do tratamento do diabetes.

Nueva generación de insulinas: glargina U300: Resumen de evidencia clínica / New generation of insulins: glargine U300. Summary of clinical evidence

La diabetes mellitus tipo 2 tiene evolución crónica y progresiva, prevalencia creciente y aún es diagnosticada tardíamente. Esto conlleva mayor incidencia de complicaciones crónicas, con incremento de costos en salud. Existe retraso en el inicio de insulinoterapia por causas relacionadas tanto al paciente como al médico. A pesar de los avances en su tratamiento, una baja proporción de enfermos logra control glucémico adecuado. La alta prevalencia de hipoglucemia en pacientes insulino-tratados, impulsó el desarrollo de una nueva generación de insulinas basales de acción prolongada, mayor estabilidad con menor variabilidad y riesgo de hipoglucemias. El programa EDITION evaluó la eficacia y seguridad de glargina U300 vs. glargina U100 en pacientes con diabetes tipo 1 y 2, en distintas etapas de la enfermedad. Glargina U300 es una nueva formulación de insulina glargina con perfil farmacocinético y farmacodinámico más estable y prolongado que glargina U100. Glargina U300 demostró eficacia y tolerabilidad comparable a glargina U100, con descenso significativo del riesgo de hipoglucemias nocturnas y en 24 horas, aportando mayor flexibilidad en el horario de inyección, con una ventana de 6 horas. Además, no se observó mayor aumento de peso que con glargina U100. El estudio Bright (2018) comparó glargina U300 vs. degludec U100, demostrando mayor beneficio en relación al riesgo de hipoglucemia con Gla-300 durante el período de titulación. Gla-300 es una insulina basal de última generación, disponible para mejorar el control metabólico, con menor riesgo de hipoglucemia.

Type 2 diabetes is a chronic, progressive disease with increasing prevalence and still late diagnostic. This leads to an increase in the incidence of chronic complications, with signifi cantly increasing health costs. There is also a delay in the onset of insulin therapy in patients with type 2 diabetes for causes related to both patients and physicians. Despite advances in treatment, a low proportion of patients achieve adequate glycemic control. The high hypoglycemia prevalence, consequence of insulin, has led to the development of a new generation long-acting basal insulins to achieve a more stable and prolonged action profile, reducing the variability and risk of hypoglycemia. The EDITION program evaluated the efficacy and safety of glargine U300 compared to glargine U100 in patients with type 1 and 2 diabetes at different stages of the disease. Gla-300 is a new formulation of insulin glargine which has a more stable and prolonged pharmacokinetic and pharmacodynamic profile. Gla-300 demonstrated efficacy and tolerability comparable to glargine U100, with a significant decrease in the risk of hypoglycemia, at night and in 24 hours, providing greater flexibility in the injection schedule, with a window of 6 hours. No increase in weight was observed compared to glargine U100. Bright study (2018) compared glargine U300 vs. degludec U100, demonstrating greater benefit in relation to the risk of hypoglycemia with Gla-300 during titration period. Gla-300 is a last-generation basal insulin, available to improve metabolic control, with a lower risk of hypoglycemia.

Safety and efficacy of a basal-plus regimen with insulin glargine and insulin glulisine for elderly patients with high cardiovascular risk and type 2 diabetes mellitus. / Eficacia y seguridad de una pauta basal plus con insulina glargina e insulina glulisina en pacientes ancianos de alto riesgo cardiovascular con diabetes mellitus tipo 2.

OBJECTIVES: To assess the safety and efficacy of a basal-plus (BP) regimen with insulin glargine (as basal insulin) and insulin glulisine (as prandial insulin) with the main meal for elderly patients with type 2 diabetes mellitus (DM2) and high cardiovascular risk, following standard clinical practice. PATIENTS AND METHODS: An observational, retrospective study was conducted in 21 centres of internal medicine in Spain. The study included patients aged 65 years or older with DM2, undergoing treatment with a BP regimen for 4 to 12 months before inclusion in the study and a diagnosis of cardiovascular disease or high cardiovascular risk. The primary endpoint was the change in glycated haemoglobin (HbA1c) from the introduction of the glulisine to inclusion in the study. RESULTS: The study included 198 patients (mean age, 74±6.4 years; males, 52%). After at least 4 months of treatment with the BP regimen, started with the addition of glulisine, the mean HbA1c value decreased significantly (9±1.5% vs. 7.7±1.1%; P<.001), and almost 24% of the patients reached HbA1c levels of 7.5-8%. Furthermore, blood glucose levels under fasting conditions decreased significantly (190.6±73.2mg/dl vs. 138.9±38.2mg/dl; P<.001). A total of 35 patients (17.7%) had some hypoglycaemia during the month prior to the start of the study, and 2 cases (1.01%) of severe hypoglycaemia were detected. CONCLUSIONS: The BP strategy could significantly improve blood glucose control in patients 65 years of age or older with DM2 and high cardiovascular risk and is associated with a low risk of severe hypoglycaemia.

[New insulin types in type 1 diabetes mellitus]. / Nuevas insulinas en la diabetes tipo 1.

Since its discovery almost a century ago, insulin remains the mainstay of treatment of patients with type 1 diabetes mellitus. Although progress in the synthesis of new formulations has been remarkable, the physiological profile of insulin is still different from that observed with preparations available nowadays. In the last decade, the introduction into clinical practice of insulin analogues has allowed significantly improvement in glycemic control and has facilitated the spread of basal/bolus patterns, the most physiological ones until now. Despite the benefits of basal analogues, glycemia often varies considerably when used as a single daily injection and this is why new molecules have been further investigated. Improvement has been achieved especially in terms of duration and rate of hypoglycemia, the main limiting factor of intensive therapy. This article reviews the available data concerning the new basal insulin analogues, degludec, pegylated lispro and glargine U300, and new formulations currently under development.

Adherencia terapéutica y flexibilidad en el uso de las insulinas basales

Desde 1921, los beneficios alcanzados por las investigaciones sobre insulinoterapia han sido constantes. Sin embargo, el temor a las hipoglucemias y la rigidez horaria para administrar la insulina aún interfieren sobre la adherencia al tratamiento, que es esencial para lograr un buen control de la glucemia y minimizar las complicaciones en los pacientes con diabetes. En este contexto, se analiza la posibilidad de utilizar un análogo de insulina ultra-lento (degludec) que posee un perfil farmacocinético prolongado y predecible por más de 24 horas. En ensayos clínicos demostró que, al administrarlo en un esquema de dosis flexible mantiene un buen control de la glucemia, sin que aumente el riesgo de hipoglucemias. Si bien en la práctica clínica es aconsejable seguir un plan establecido, la posibilidad de flexibilizar el horario en la aplicación diaria del análogo ultra-lento en caso de ser necesario, podría mejorar la adherencia en pacientes con una vida social y laboral activa y poco previsible.

Since 1921, the benefits achieved by insulin therapy research have been constant. However, the fear of a hypoglycemia incidence and rigid time schedules of insulin therapy still interfere with treatment adherence, which is essential to achieve optimal glycemic control and minimize complications in diabetic patients. The possibility of using an ultra long-acting insulin analogue (degludec), which has an extensive and predictable pharmacokinetic profile over 24 hours, is analyzed in this context. Clinical trials have shown that this ultra long-acting insulin analogue administered in a flexible dosage treatment, reached a good glycaemic control with no increase on hypoglycemia risk. Although to follow a predefined plan in clinical practice is recommended, the possibility of flexibility in day to day dosage timing of this specific insulin analogue on requirement, could improve adherence in patients with a non-predictable and active social life and workday.

Adherencia terapéutica y flexibilidad en el uso de las insulinas basales

Desde 1921, los beneficios alcanzados por las investigaciones sobre insulinoterapia han sido constantes. Sin embargo, el temor a las hipoglucemias y la rigidez horaria para administrar la insulina aún interfieren sobre la adherencia al tratamiento, que es esencial para lograr un buen control de la glucemia y minimizar las complicaciones en los pacientes con diabetes. En este contexto, se analiza la posibilidad de utilizar un análogo de insulina ultra-lento (degludec) que posee un perfil farmacocinético prolongado y predecible por más de 24 horas. En ensayos clínicos demostró que, al administrarlo en un esquema de dosis flexible mantiene un buen control de la glucemia, sin que aumente el riesgo de hipoglucemias. Si bien en la práctica clínica es aconsejable seguir un plan establecido, la posibilidad de flexibilizar el horario en la aplicación diaria del análogo ultra-lento en caso de ser necesario, podría mejorar la adherencia en pacientes con una vida social y laboral activa y poco previsible.(AU)

Since 1921, the benefits achieved by insulin therapy research have been constant. However, the fear of a hypoglycemia incidence and rigid time schedules of insulin therapy still interfere with treatment adherence, which is essential to achieve optimal glycemic control and minimize complications in diabetic patients. The possibility of using an ultra long-acting insulin analogue (degludec), which has an extensive and predictable pharmacokinetic profile over 24 hours, is analyzed in this context. Clinical trials have shown that this ultra long-acting insulin analogue administered in a flexible dosage treatment, reached a good glycaemic control with no increase on hypoglycemia risk. Although to follow a predefined plan in clinical practice is recommended, the possibility of flexibility in day to day dosage timing of this specific insulin analogue on requirement, could improve adherence in patients with a non-predictable and active social life and workday.(AU)

Degludec, a new ultra-long-acting basal insulin for the treatment of diabetes mellitus type 1 and 2: advances in clinical research.

Degludec is the most recent molecule of the ultra-long-acting basal insulin analogues approved for human use. It forms soluble multihexamers which after subcutaneous injection are converted into monomers, and are thus slowly and continuously absorbed into the bloodstream. This absorption mechanism confers degludec an ultra-long and stable action profile, with no concentration peaks. This paper discusses the most recent studies in patients with type 1 and 2 diabetes mellitus, which showed degludec to be non inferior in decreasing HbA1c, ensuring optimum glycemic control similar to that achieved with insulin glargine or detemir. Degludec also had an improved safety profile, as it was associated to a significantly lower rate of nocturnal hypoglycemia in both types of diabetes and to a potentially lower overall hypoglycemia rate in type 2 DM. Degludec also opens the possibility to use more flexible regimens.

Lipoproteína (a) está associada com níveis basais de insulina em pacientes com Diabetes Mellitus tipo 2 / Lipoproteína (a) está asociada a niveles basales de insulina en pacientes con Diabetes Mellitus tipo 2 / Lipoprotein (a) is associated with basal insulin levels in patients with type 2 Diabetes Mellitus

FUNDAMENTO: Ainda não foi claramente estabelecido se a resistência/deficiência insulínica leva diretamente à aterogênese ou através de sua associação com outros fatores de risco como os níveis de lipoproteína (a)[Lp(a)]. OBJETIVO: O objetivo do estudo foi estabelecer a relação entre os níveis basais de insulina, lípides e lipoproteína (a) em pacientes com diabetes mellitus (DM) tipo 2. MÉTODOS: Amostras de sangue foram colhidas em jejum e os níveis de insulina, lipoproteína (a), colesterol total (CT), triglicérides (TG), lipoproteína de baixa densidade (LDL-C), lipoproteína de alta densidade (LDL-C), glicose e hemoglobina glicada (HbA1c) foram medidos em 60 pacientes com DM tipo 2 e 28 indivíduos saudáveis. Nós dividimos os pacientes em dois grupos baseados nos níveis basais de insulina: > 10 µIU/ml e < 10 µIU/ml. RESULTADOS: Os níveis de insulina eram mais altos nos indivíduos diabéticos do que nos controles [p < 0,05]. Os níveis de CT (p< 0,01), LDL-C (p< 0,05), razão CT/HDL (p< 0,01), e TG (p< 0,05) eram mais altos e os níveis de HDL- C eram significantemente mais baixos em ambos os grupos de diabéticos, quando comparados aos controles. Os níveis de Lp(a) eram significantemente mais baixos em diabéticos com insulina basal > 10 µIU/ml comparados com aqueles que apresentavam insulina basal < 10 µIU/ml (p < 0.05). A análise de regressão mostrou uma relação significante da Lp(a) com os níveis de insulina (r = 0,262, p < 0,05) e razão Insulina/Glicose(r = 0,257, p < 0,05). CONCLUSÃO: Os níveis de Lp(a) se correlacionam inversamente com os níveis de insulina em pacientes com DM tipo 2. Os níveis de Lp(a) podem ser um dos fatores de risco cardiovascular em pacientes com DM tipo 2 com maior duração da doença. (Arq Bras Cardiol 2009;93(1):28-33)

BACKGROUND: It has not been clearly established whether insulin resistance/deficiency leads directly to atherogenesis or through its association with other risk factors such as Lipoprotein(a) [Lp(a)]. OBJECTIVE: This project aimed at studying the association between basal Insulin, Lipids and Lipoprotein(a) levels in Patients with Type 2 Diabetes Mellitus. METHODS: Fasting blood samples were analyzed for Insulin, Lipoprotein(a), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), glucose and glycosylated hemoglobin (HbA1c) levels in 60 patients with type 2 Diabetes Mellitus (DM) and 28 healthy subjects. We divided patients into two groups based on basal insulin levels: > 10 µIU/ml and < 10 µIU/ml. RESULTS: Insulin levels were higher in diabetic versus control individuals [p < 0.05]. TC (p< 0.01), LDL-C (p< 0.05), TC/HDL ratio (p< 0.01) and TG levels (p< 0.05) were higher and HDL- C levels were significantly lower (p < 0.001) in both diabetic groups as compared to control. Lp(a) levels were significantly higher in both diabetic groups, when compared to the control group. Lp(a) levels were significantly lower in diabetics with basal insulin > 10 µIU/ml when compared to those with basal insulin < 10 µIU/ml (p < 0.05). Regression analysis revealed a significant relationship of Lp(a) with insulin levels (r = 0.262, p < 0.05) and Insulin Glucose ratio (r = 0.257, p < 0.05). CONCLUSION: Lp(a) levels correlate inversely with insulin levels in Type 2 diabetic patients. Lp(a) may be one of the cardiovascular risk factor in type 2 diabetic patients with longer duration of DM.

FUNDAMENTO: Todavía no se aclaró totalmente si la resistencia/deficiencia insulínica lleva directamente a la aterogénesis o a través de su asociación con otros factores de riesgo como los niveles de lipoproteína (a) [Lp(a)]. OBJETIVO: : El objetivo del estudio fue establecer la relación entre los niveles basales de insulina, lípidos y lipoproteína (a) en pacientes con diabetes mellitus (DM) tipo 2. MÉTODOS: Se extrajeron muestras de sangre en ayuno y se determinaron los niveles de insulina, lipoproteína (a), colesterol total (CT), triglicéridos (TG), lipoproteína de baja densidad (LDL-C), lipoproteína de alta densidad (LDL-C), glucosa y hemoglobina glicosilada (HbA1c) en 60 pacientes con DM tipo 2 y 28 individuos sanos. Dividimos a los pacientes en dos grupos basados en los niveles basales de insulina: > 10 µIU/ml y < 10 µIU/ml. RESULTADOS: : Los niveles de insulina eran más altos en los individuos diabéticos que en los controles [p < 0,05]. Los niveles de CT (p< 0,01), LDL-C (p< 0,05), razón CT/HDL (p< 0,01), y TG (p< 0,05) eran más altos y los niveles de HDL- C eran significantemente más bajos en ambos grupos de diabéticos, cuando comparados a los controles. Los niveles de Lp(a) eran significantemente más bajos en diabéticos con insulina basal > 10 µIU/ml comparados con aquellos que presentaban insulina basal < 10 µIU/ml (p < 0.05). El análisis de regresión evidenció una relación significante de la Lp(a) con los niveles de insulina (r = 0,262, p < 0,05) y razón insulina glucosa(r = 0,257, p < 0,05). CONCLUSIÓN: Los niveles de Lp(a) se correlacionan inversamente con los niveles de insulina en pacientes con DM tipo 2. Los niveles de Lp(a) pueden ser uno de los factores de riesgo cardiovascular en pacientes con DM tipo 2 con mayor duración de la enfermedad.

Análogos en el Régimen Basal/Bolo: Insulinización oportuna en diabetes tipo 2

La diabetes es una patología difícil de tratar. Actualmente la insulina sigue siendo el pilar fundamental, y las estrategias de tratamiento de reemplazo tienen por finalidad reproducir el perfil de secreción normal de insulina, para lograr así el control efectivo en los niveles de glucemia basal y postprandial. Con una combinación adecuada de análogos de insulina, se puede lograr ése control óptimo de la glucemia, recomendado por las diferentes asociaciones y organizaciones mundiales, dedicadas al estudio y control de la diabetes. En este artículo se realiza una revisión sobre la fisiopatología de la diabetes mellitus Tipo 1 y Tipo 2, como base para dirigir el tratamiento usando las nuevas insulinas (análogos), en cada una de ellas. Pero necesitamos superar los mitos y las barreras, que tienen los médicos y sus pacientes, a los regímenes de tratamiento con insulina.

Diabetes is a difficult disease to treat. Currently, insulin is still the mainstay. Treatment strategies are aimed to reproduce the normal secretory profile of insulin to achieve the effective control in the fasting and postprandial plasma glucose levels. Mostly, with an appropriate combination of insulin analogues, an optimal control of blood sugar could be achieved, such as recommended by the different worldwide associations and organizations, dedicated to the study and control care of diabetes. This article is a review of the pathophysiology of Type 1 and Type 2 diabetes mellitus as the support for treatment in each one of its, but we still need to dispel myth and removing barriers of acceptance about these insulin regimens treatments in physicians and patients.