Algunas características del tratamiento con insulina en el paciente con diabetes mellitus tipo 2 / Some Characteristics of Insulin Treatment in Patients with Type 2 Diabetes Mellitus

Introducción: La insulina es un importante fármaco que puede ser empleado en el tratamiento del paciente diabetes mellitus tipo 2. Objetivo: Describir algunas de las características del tratamiento con insulina en el paciente con diabetes mellitus tipo 2. Métodos: La información necesaria para redactar el presente artículo se obtuvo en el trimestre octubre-diciembre de 2020. Se utilizó como motores de búsqueda de información científica a Google Académico, Pubmed y Scielo. Se evaluaron diferentes trabajos de revisión, de investigación y páginas web, que en general tenían menos de 10 años de publicados, en idioma español, portugués o inglés. Fueron utilizadas como palabras clave: tratamiento; insulina; análogos de insulina; diabetes mellitus. Fueron excluidos los artículos que no reunían las condiciones señaladas. Esto permitió el estudio de 80 artículos, de los cuales 43 fueron referenciados. Conclusiones: La insulina es una hormona polipeptídica sintetizada por las células β de los islotes de Langerhans del páncreas. Su efecto es ejercido fundamentalmente a nivel del hígado, tejido adiposo y músculo, y es una opción terapéutica en cualquier fase evolutiva de la diabetes mellitus tipo 2, cuando los agentes orales no logran las metas o si se presentan ciertas complicaciones. Se dispone de una amplia gama de tipos de insulina con distintos perfiles de acción y concentración, lo que permite clasificarlas de diferentes maneras. Se han establecido diferentes criterios sobre cuándo se debe comenzar y cómo orientar el tratamiento con insulina en la persona con diabetes mellitus tipo 2, lo que hacen posible un mejor control glucémico(AU)

Introduction: Insulin is an important drug that can be used for providing treatment to the patient with type 2 diabetes mellitus. Objective: To describe some of the characteristics of insulin treatment in patients with type 2 diabetes mellitus. Methods: The necessary information for writing this article was obtained in the trimester October-December 2020. As search engines for scientific information, Google Scholar, Pubmed and SciELO were used. Different review papers, research papers and web pages were assessed, generally less than ten years old and published in Spanish, Portuguese or English. The following keywords were used: tratamiento [treatment], insulina [insulin]; análogos de insulina [insulin analogues], diabetes mellitus. The articles not meet the above conditions were excluded. This allowed the study of eighty articles, of which 43 were referenced. Conclusions: Insulin is a polypeptide hormone synthesized by the β cells of the islets of Langerhans of the pancreas. Its effect is produced primarily at the liver, adipose tissue and muscle levels. It is a therapeutic option in any evolutionary phase of type 2 diabetes mellitus, when oral agents fail to achieve goals or if certain complications occur. A wide range of insulin types with different action and concentration profiles are available, allowing them to be classified in different ways. Different criteria have been established about when to start and how to guide insulin treatment in the person with type 2 diabetes mellitus, making better glycemic control possible(AU)

El estudio A1chieve: un estudio observacional, de no intervención en pacientes con diabetes tipo 2 que inician o cambian a un tratamiento con análogos de insulina: datos de la población argentina / The A1chieve study: An observational non-interventional study of patients with type 2 diabetes initiating or changing to insulin analogue therapy: data from the Argentinean population

Objetivos: el objetivo de este artículo es informar acerca de la seguridad y la efectividad de iniciar o cambiar a un tratamiento con insulinas análogas en la subpoblación argentina del estudio A1chieve. Materiales y métodos: estudio observacional, de no intervención. En la cohorte argentina participaron 607 pacientes con diabetes tipo 2 (DM2), con o sin tratamiento previo con insulina, quienes inciaron un tratamiento con insulina aspártica bifásica 30, insulina detemir o insulina aspártica con o sin antidiabéticos orales (ADOs). Resultados: el grado de control metabólico al inicio del estudio, medido por HbA1c basal (± DE) fue pobre: 9,4 ± 2,1 %. A los 6 meses, se observó una reducción de HbA1c de -1,8 ± 2,1 % en la cohorte completa, y -2,3 ± 2,1% y -1,1 ± 1,8 % para los pacientes sin tratamiento previo con insulina y con tratamiento previo con insulina, respectivamente. En general, la tasa de hipoglucemia se incrementó en aquellos pacientes que recibieron insulina por primera vez, mientras que se observó una disminución en los pacientes que, previamente, recibían otras insulinas. Se observó un incremento del peso corporal (± DE) en los pacientes sin tratamiento previo con insulina (0,8 ± 4,3 kg). Conclusiones: en la población argentina del estudio A1chieve, se observó un control metabólico deficiente. Se logró una mejoría de la HbA1c al iniciar un tratamiento con análogos de insulina, ya sea en pacientes naïve usuarios previos de insulina,siendo una gran oportunidad para lograr amplias mejorías en el autocuidado y en el control metabólico, independientemente del tipo de regimen insulínico utilizado, con buena tolerabilidad y seguridad. Estos hallazgos coinciden con los resultados obtenidos en la cohorte completa del estudio.

Objectives: The aim of this paper is to report the safety and effectiveness of initiating or switching to insulin analogue therapy in the Argentinean subpopulation of the A1chieve study. Materials and methods: Observational, non-interventional study. The Argentinean cohort included 607 patients with type 2 diabetes (T2D), both insulin-naïve and prior insulin users, who initiated treatment with biphasic insulin aspart 30, insulin detemir or insulin aspart ± oral antidiabetic agents. Results: Baseline HbA1c (±SD) was poor: 9.4 ± 2.1 %. At 6 months, a reduction in the HbA1c of -1.8 ± 2.1 % was observed in the entire cohort, and of -2.3 ± 2.1 % and -1.1 ± 1.8 % in insulin-naïve patients and prior insulin users, respectively. Overall, the rate of hypoglycaemia increased in insulin-naïve patients, whereas a reduction was observed in those switching from other insulins. An increase in the body weight (±SD) was noted in insulin-naïve patients (0.8 ± 4.3 kg). Conclusions: Poor glycemic control was observed in the Argentinean population of the A1chieve study. The initiation of insulin analogue therapy showed an improvement in HbA1c, in both insulin-naïve patients and previous insulin users, which was a good opportunity for improvements in self-care and metabolic control, regardless of the type of insulin regimen used, with a good tolerability and safety profile. These findings are consistent with those obtained from the entire A1chieve study cohort.

Insulin analogues in the treatment of diabetes in pregnancy / Análogos de insulina no tratamento do diabetes gestacional

Pregnancy affects both maternal and fetal metabolism, and even in non-diabetic women, it exerts a diabetogenic effect. Among pregnant women, 2% to 14% develop gestational diabetes. Pregnancy can also occur in women with preexisting diabetes, which may predispose the fetus to many alterations in organogenesis, restrict growth, and the mother, to some diabetes-related complications, such as retinopathy and nephropathy, or to acceleration of the course of these complications, if they are already present. Women with gestational diabetes generally start their treatment with diet and lifestyle changes; when these changes are not enough for optimal glycemic control, insulin therapy must then be considered. Women with type 2 diabetes using oral hypoglycemic agents are advised to change to insulin therapy. Those with preexisting type 1 diabetes should start intensive glycemic control. As basal insulin analogues have frequently been used off-label in pregnant women, there is a need to evaluate their safety and efficacy. The aim of this review is to report the use of both short- and long-acting insulin analogues during pregnancy and to enable clinicians, obstetricians, and endocrinologists to choose the best insulin treatment for their patients.

A gravidez afeta tanto o metabolismo materno quanto o fetal e, mesmo em mulheres não diabéticas, apresenta um efeito diabetogênico. Entre as mulheres grávidas, 2% a 14% desenvolvem o diabetes gestacional. A gravidez pode ocorrer também em mulheres já diabéticas, o que pode predispor o feto a muitas alterações na organogênese, restrição de crescimento e a mãe a algumas complicações relacionadas ao diabetes, tais como retinopatia e nefropatia, ou acelerar o curso dessas complicações se já estiverem presentes. Pacientes com diabetes gestacional geralmente iniciam seu tratamento com dieta e mudanças no estilo de vida; porém, quando essas medidas falham em atingir um controle glicêmico adequado, a insulinoterapia deve ser considerada. Pacientes com diabetes tipo 2 em uso de hipoglicemiantes orais são aconselhadas a iniciar o uso de insulina. Pacientes com diabetes tipo 1 preexistente devem iniciar um controle glicêmico estrito. Em função do fato de os análogos basais de insulina estarem sendo utilizados muito frequentemente off-label em pacientes grávidas, faz-se necessário avaliar sua segurança e eficácia nessa condição. O objetivo desta revisão é avaliar o uso de tais análogos, tanto de ação curta como prolongada, durante a gravidez, para possibilitar médicos clínicos, obstetras e endocrinologistas escolher o melhor regime terapêutico para suas pacientes.

Régimen con insulina lispro mix 25 versus insulina glargina para la diabetes tipo 2 / Starting an insulin regimen with insulin lispro mix 25 versus glargine insulin for type 2 diabetes

La información sobre el inicio de regímenes de insulina en poblaciones específicas con diabetes tipo 2 (DT2) es limitada. Se comparó eficacia y seguridad de dos regímenes de inicio: insulina lispro mix 25 (LM25) e insulina glargina basal (GL). Se evaluaron 193 pacientes no tratados previamente con insulina, en la fase de iniciación de 24 semanas del ensayo DURABLE; edades: 30-79 años, DT2 controlada inadecuadamente (HbA1c > 7.0%) con = 2 medicaciones orales antidiabéticas (MOAs), aleatorizados para LM25 (25% de insulina lispro, 75% de insulina lispro protamina en suspensión) dos veces/día, o GL (insulina glargina basal) una vez/ día, a las MOAs previas. La eficacia primaria se midió por HbA1c a las 24 semanas. Se midió eficacia secundaria por: proporción de pacientes que alcanzaron HbA1c= 6.5% y= 7.0%, cambio en peso corporal, valores de automonitoreo glucémico e índices de hipoglucemia. LM25 demostró mayor reducción de la HbA1c (- 2.4% ± 0.16 vs. -2.0% ± 0.16, P = 0.002), mayor proporción de pacientes alcanzaron HbA1c= 7.0% (P = 0.012) y niveles de glucemia menores después del desayuno (P = 0.028) y de la cena (P = 0.011), y a las 3 a.m. (P = 0.005) comparada con GL. La glucemia en ayunas (GA) y la proporción de pacientes que alcanzaron una HbA1c= 6.5% fueron similares. En ambos grupos hubo aumento del peso corporal, mayor en la valoración final con LM25 (6.35 kg vs. 4.23 kg, P < 0.001). No hubieron diferencias en índices de hipoglucemia entre grupos, ni eventos adversos serios en ninguno. Con LM25 fue mejor el control de glucosa, riesgo de hipoglucemia similar y mayor aumento de peso que GL.

Information on starting insulin regimens in specific populations with type 2 diabetes (T2D) is limited. This analysis compared efficacy and safety of two starter insulin regimens: insulin lispro mix 25 (LM25) and basal insulin glargine (GL) in patients from Argentina. This post-hoc analysis evaluated 193 insulin-naïve patients who participated in the DURABLE trial 24-week initiation phase. Patients 30-79 years with T2D inadequately controlled (HbA1c > 7.0%) with = 2 oral antihyperglycemic medications (OAMs), were randomized to add LM25 (25% insulin lispro, 75% insulin lispro protamine suspension) twice daily or GL (basal insulin glargine) once daily to pre-study OAMs. Primary efficacy was measured by HbA1c at 24-week endpoint. Secondary measures included: proportion of patients achieving HbA1c= 6.5% and= 7.0%, body weight change, self-monitored blood glucose (BG) values, and hypoglycemia rates. LM25 demonstrated greater HbA1c reduction (- 2.4% ± 0.16 vs. -2.0% ± 0.16, P = 0.002), a higher proportion of patients achieving HbA1c= 7.0% (P = 0.012), and lower BG levels after the morning (P = 0.028) and evening (P = 0.011) meals, and at 3:00AM (P = 0.005) compared with GL. Fasting BG and proportion of patients achieving HbA1c= 6.5% were similar between groups. Both groups increased body weight, although the gain was higher at endpoint with LM25 (6.35 kg vs. 4.23 kg, P < 0.001). No differences in hypoglycemia rates were observed between groups, and no serious adverse events were reported for either group. In this subgroup from Argentina, LM25 demonstrated greater improvement in glucose control with similar risk of hypoglycemia and more weight gain than GL.

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.

Novas opções na terapia insulínica: [revisão] / New options in insulin therapy: [review]

OBJETIVO: Revisar as novas opções nas terapêuticas insulínicas para controlar o diabetes melito de crianças e adolescentes. FONTES DOS DADOS: Foram revisados artigos indexados no PubMed buscados conforme as palavras insulin analogs in children and adolescents e incluídas informações contidas nos consensos da American Diabetes Association e Sociedade Brasileira de Diabetes. SÍNTESE DOS DADOS: São apresentadas informações sobre os novos análogos da insulina e, para comparação, são também revisadas as outras diferentes modalidades de insulina que estão atualmente disponíveis, focalizando nas terapias insulínicas que tentam fornecer uma aproximação mais fisiológica das estratégias basal-bolos no tratamento. Com o objetivo de obter melhor controle metabólico, mais e mais crianças estão em regimes de múltiplas injeções diárias ou usando infusões subcutâneas contínuas de insulina. Atingir controle glicêmico ótimo nas crianças é difícil devido ao maior risco de hipoglicemia decorrente da grande variabilidade em hábitos de ingerir alimentos e em níveis de atividade física. Se aplicados em bolos, subcutâneos, no diabetes tipo 1, os análogos de ação rápida, comparados com insulina humana regular, geralmente reduzem os episódios de hipoglicemia e glicemia pós-prandial, enquanto os análogos basais tendem a reduzir particularmente a hipoglicemia noturna. CONCLUSÃO: Embora os benefícios nos desfechos individuais metabólicos e clínicos pareçam modestos, a maioria dos estudos demonstra benefícios quando são usados análogos de insulina no tratamento do diabetes tipo 1 ou 2.

OBJECTIVE:To review the new options in insulin therapy for controlling diabetes mellitus in children and adolescents. SOURCES: Articles indexed in PubMed were located using the search terms insulin analogs in children and adolescents and reviewed. Information was also obtained from American Diabetes Association and Sociedade Brasileira de Diabetes consensus documents. SUMMARY OF THE FINDINGS: Information is presented on new analogs of insulin and, for purposes of comparison, the other insulin modalities currently available are also reviewed, focusing on insulin therapies which attempt to approximate basal-bolus treatment strategies to physiology. With the objective of obtaining improved metabolic control, more and more children are being put on multiple daily injection regimes or using continuous subcutaneous insulin infusion. It is difficult to achieve optimum glycemic control in children due to the increased risk of hypoglycemia resulting from the great variability in dietary intake habits and in physical activity levels. With diabetes type 1, if rapid-acting analogs are given subcutaneously in bolus, they generally reduce hypoglycemia episodes and postprandial glycemia levels, compared with regular human insulin, while basal analogs tend to reduce particularly the number of episodes of nocturnal hypoglycemia. CONCLUSIONS: Although the benefits to individual metabolic and clinical outcomes appear modest, the majority of studies demonstrate benefits when insulin analogs are used in the treatment of diabetes type 1 or 2.