Insulinas análogas de ação prolongada comparadas à insulina NPH para tratamento de diabetes mellitus tipo 2 em adultos: revisão rápida / Long-acting basal insulin analogues compared to nph insulin for type 2 diabetes mellitus in adults: rapid review

Tecnologia: Insulinas análogas de liberação prolongada versus insulina NPH (protamina neutra de Hagedorn). Indicação: Tratamento de adultos com diabetes mellitus tipo 2. Pergunta: Há diferenças de efeito nos principais desfechos de eficácia e segurança entre insulinas análogas de liberação prolongada versus insulina NPH no tratamento de pacientes com DM2? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foi selecionada e incluída uma revisão sistemática. Conclusão: As insulinas análogas (glargina e detemir) não demonstraram superioridade nos desfechos de eficácia e segurança quando comparadas à insulina NPH, não demonstraram redução significativa em relação à mortalidade por todas as causas e complicações secundárias ao DM2. Quando comparadas à insulina NPH, foi observado redução na hipoglicemia confirmada e hipoglicemia noturna a favor das insulinas análogas e na hipoglicemia grave a favor da insulina detemir

Technology: Long-acting insulin analogues versus NPH insulin (human isophane insulin). Indication: Treatment of adults with type 2 diabetes mellitus. Question: Are there effect differences in key efficacy and safety outcomes between long-acting insulin analogues versus NPH insulin in the treatment of DM2 patients? Methods: Rapid review of evidence (overview) of systematic reviews, with a bibliographic survey carried out in the PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Results: A systematic review was selected and included. Conclusion: Analog insulins (glargine and detemir) did not demonstrate superiority in efficacy and safety outcomes when compared to NPH insulin, did not demonstrate a significant reduction in all-cause mortality and complications secondary to DM2. When compared to NPH insulin, a reduction in confirmed hypoglycemia and nocturnal hypoglycemia in favor of analogue insulins and in severe hypoglycemia in favor of insulin detemir was observed

Underutilization of insulin and better metabolic control. A NOVA clinic experience

SUMMARY OBJECTIVE To present the results of metabolic control in patients with type 2 Diabetes Mellitus from a private clinic in Northern Mexico, METHODS This cross-sectional study used retrospective data obtained from electronic records from a private outpatient clinic at the end of 2018. Inclusion criteria were a diagnosis of T2DM and age ≥ 18 years. Baseline characteristics (age, gender, drug use) were reported. The achievement of glycated hemoglobin goals was established as <7%. RESULTS A total of 3820 patients were evaluated. Their mean age was 59.86 years (+/-15.01). Of the population, 46.72% were men, and 53.28% were women. Glycated hemoglobin goals were adequate in 1872 (54%) patients. There were 3247 patients (85%) treated with oral medications, of which 1948 (60%) reported glycated hemoglobin less than 7%. Insulin use was reported in 573 (15%) patients, with 115 (20%) reporting glycated hemoglobin less than 7%. The most frequently used basal insulin was glargine in 401 (70%) patients. CONCLUSIONS Our findings are clearly higher than the control rate reported by our national health surveys of 25% with glycated hemoglobin < 7%, but similar to that reported in other countries. The most commonly used therapeutic scheme was the combination of oral hypoglycemic agents. The percentage of cases that include insulin in their treatment was lower. Clinical inertia to insulin initiation and intensification has been defined as an important cause of this problem.

RESUMO OBJETIVO Apresentar os resultados do controle metabólico de pacientes com Diabetes Mellitus tipo 2 em uma clínica privada no norte do México, MÉTODOS Este estudo transversal utilizou dados retrospectivos obtidos em prontuários eletrônicos de um ambulatório privado no final de 2018. Os critérios de inclusão foram o diagnóstico de DM2 e idade ≥ 18 anos. Características basais (idade, sexo, uso de drogas) foram relatadas. A realização de metas de hemoglobina glicada foi estabelecida como <7%. RESULTADOS Um total de 3820 pacientes foram avaliados. A média de idade foi de 59,86 anos (+/- 15,01). Da população, 46,72% eram homens e 53,28% eram mulheres. Objetivos de hemoglobina glicada foram adequados em 1872 (54%) pacientes. Havia 3247 pacientes (85%) tratados com medicamentos orais relatando em 1948 (60%) menos de 7%. O uso de insulina foi relatado em 573 (15%) pacientes, com 115 (20%) relatando menos de 7%. A insulina basal mais utilizada foi a glargina, em 401 (70%) pacientes. CONCLUSÕES Nossos resultados são claramente mais altos do que a taxa de controle relatada por nossos levantamentos nacionais de saúde de 25% com hemoglobina glicada <7%, mas semelhante à relatada em outros países. O esquema terapêutico mais utilizado foi a combinação de hipoglicemiantes orais. A porcentagem de casos que incluem insulina no tratamento foi menor. A inércia clínica à iniciação e intensificação da insulina tem sido definida como uma importante causa desse problema.

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.

Effectiveness of insulin analogs compared with human insulins in pregnant women with diabetes mellitus: systematic review and meta-analysis / Efetividade dos análogos da insulina comparados às insulinas humanas em gestantes com diabetes mellitus: Revisão sistemática com metanálise

Abstract Diabetes during pregnancy has been linked to unfavorable maternal-fetal outcomes. Human insulins are the first drug of choice because of the proven safety in their use. However, there are still questions about the use of insulin analogs during pregnancy. The objective of the present study was to determine the effectiveness of insulin analogs compared withhuman insulin in the treatment of pregnant women with diabetes througha systematic review withmeta-analysis. The search comprised the period since the inception of each database until July 2017, and the following databases were used:MEDLINE, CINAHL, EMBASE, ISIWeb of Science, LILACS, Scopus, SIGLE andGoogle Scholar.We have selected 29 original articles: 11 were randomized clinical trials and 18 were observational studies.We have explored data from 6,382 participants. All of the articles were classified as having an intermediate to high risk of bias. The variable that showed favorable results for the use of insulin analogs was gestational age, with a mean difference of - 0.26 (95 % confidence interval [CI]: 0.03-0.49; p = 0.02), but with significant heterogeneity (Higgins test [I2] = 38%; chi-squared test [χ2] = 16.24; degree of freedom [DF] = 10; p = 0.09). This result, in the clinical practice, does not compromise the fetal well-being, since all babies were born at term. There was publication bias in the gestational age and neonatal weight variables. To date, the evidence analyzed has a moderate-to-high risk of bias and does not allow the conclusion that insulin analogs are more effective when compared with human insulin to treat diabetic pregnant women.

Resumo Diabetes durante a gestação tem sido relacionado a desfechos materno-fetais desfavoráveis. As insulinas humanas são a primeira escolha medicamentosa, devido à comprovada segurança no seu uso. Entretanto, ainda há questionamentos sobre o uso dos análogos da insulina na gestação. O objetivo do presente estudo foi determinar a efetividade dos análogos da insulina comparados às insulinas humanas no tratamento de gestantes com diabetes por meio de uma revisão sistemática com metanálise. A busca compreendeu desde o início de cada base de dados até julho de 2017, e foi realizada nos seguintes bancos de dados: MEDLINE, CINAHL, EMBASE, ISI Web of Science, LILACS, Scopus, SIGLE e Google Scholar. Selecionamos 29 artigos originais, sendo 11 ensaios clínicos randomizados e 18 estudos observacionais. Exploramos dados de 6.382 participantes. Todos os artigos foram classificados como sendo de intermediário a alto risco de viés. A variável que demonstrou resultado favorável ao uso dos análogos da insulina foi idade gestacional, com uma diferençamédia de - 0.26 (95% índice de confiança [IC]: 0.03-0.49; p = 0.02), porém com heterogeneidade significativa (teste de Higgins [I2] = 38%; teste do qui quadrado [χ2] =16.24; graus de liberdade [GL] =10; p = 0.09). Esse resultado, na prática clínica, não compromete o bem-estar fetal, uma vez que todos os bebês nasceram a termo. Houve viés de publicação nas variáveis idade gestacional e peso neonatal. Até o momento, as evidências analisadas possuem um risco de viés moderado a elevado e não permitem concluir que os análogos da insulina sejam mais efetivos em comparação às insulinas humanas para tratar gestantes diabéticas.

Effectiveness and Safety of Adding Basal Insulin Glargine in Patients with Type 2 Diabetes Mellitus Exhibiting Inadequate Response to Metformin and DPP-4 Inhibitors with or without Sulfonylurea

BACKGROUND: We aimed to investigate the effectiveness and safety of adding basal insulin to initiating dipeptidyl peptidase-4 (DPP-4) inhibitor and metformin and/or sulfonylurea (SU) in achieving the target glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM). METHODS: This was a single-arm, multicenter, 24-week, open-label, phase 4 study in patients with inadequately controlled (HbA1c ≥7.5%) T2DM despite the use of DPP-4 inhibitor and metformin. A total of 108 patients received insulin glargine while continuing oral antidiabetic drugs (OADs). The primary efficacy endpoint was the percentage of subjects achieving HbA1c ≤7.0%. Other glycemic profiles were also evaluated, and the safety endpoints were adverse events (AEs) and hypoglycemia. RESULTS: The median HbA1c at baseline (8.9%; range, 7.5% to 11.1%) decreased to 7.6% (5.5% to 11.7%) at 24 weeks. Overall, 31.7% subjects (n=33) achieved the target HbA1c level of ≤7.0%. The mean differences in body weight and fasting plasma glucose were 1.2±3.4 kg and 56.0±49.8 mg/dL, respectively. Hypoglycemia was reported in 36 subjects (33.3%, 112 episodes), all of which were fully recovered. There was no serious AE attributed to insulin glargine. Body weight change was significantly different between SU users and nonusers (1.5±2.5 kg vs. −0.9±6.0 kg, P=0.011). CONCLUSION: The combination add-on therapy of insulin glargine, on metformin and DPP-4 inhibitors with or without SU was safe and efficient in reducing HbA1c levels and thus, is a preferable option in managing T2DM patients exhibiting dysglycemia despite the use of OADs.

Insulina degludec en pacientes diabéticos tipo 1: observación a 18 meses / Degludec insulin in type 1 diabetic patients: 18 months of observation

Antecedentes: En el tratamiento de la diabetes se buscan insulinas de acción más prolongada y con menores tasas de hipoglicemias. Objetivo. Uso del análogo de insulina de acción ultralenta degludec en diabéticos tipo 1 (DM1) tratados previamente con glargina. Pacientes y método: Se observaron 230 DM1 durante 18 meses, promedio de edad 34 años y de diagnóstico 14 años, registrándose parámetros clínicos, bioquímicos, hipoglicemias y requerimientos de insulina (U/kg/peso), en régimen basal/bolo, con degludec y ultra-rápida precomidas. Degludec se ajustó quincenalmente. Resultados: A los 3 meses, la glicemia de ayunas disminuyó de 253mg/dl (243-270) a 180 mg/dl (172- 240), (p< 0,05); a los 6 meses a 156 mg/dl (137-180) (p< 0,05), a los 12 meses a 151 mg/dl (50-328) (p< 0,001) y a los 18 meses 150 (50-321) (p<0,001). La HbA1c, inicialmente de 10,6% (10,3-12,2) bajó a los 3 meses a 8,7% (8,2-11,1) (p< 0,05), a 6 meses a 8,3% (8,0-9,6) (p<0,05), a los 12 meses subió 9,0% (5,9-14,5) (p<0,001) y a los 18 meses 9,0% (5,9-14,6) (p<0,001). La dosis de degludec fue 0,5 U/kg/peso a los 18 meses. Hubo reducción de hipoglicemias: a los 3 meses 14 leves, 4 moderados 1 grave; a los 6 meses 8 leves, 2 moderados y ninguna grave; a los 12 meses 1 leve, y a los 18 meses 2 leves, 1 moderado y ninguna grave. Un 7,8% no presentó hipoglicemias. Conclusión: Degludec en DM1 mostró reducir las glicemias de ayunas y HbA1c, y menor número de hipoglicemias.

Background: In the treatment of diabetes, longer-acting insulins with lower rates of hypoglycaemia are sought. Objective. Use of ultralow-acting insulin analog degludec in type 1 diabetic patients (T1D) previously treated with glargine. Patients and method: 230 T1D patients were observed during 18 months, average of age 34 years and of diagnosis 14 years, registering clinical, biochemical, hypoglycemia and insulin requirements (U / kg / weight), in basal / bolus regimen, with degludec and ultra-fast pre-meals. Degludec adjusted himself fortnightly. Results: At 3 months, the fasting glycemia decreased from 253 mg / dl (243-270) to 180 mg / dl (172 - 240), (p <0.05); at 6 months at 156 mg / dl (137-180) (p <0.05), at 12 months at 151 mg / dl (50-328) (p <0.001) and at 18 months 150 (50-321) ;(p <0.001). HbA1c, initially of 10.6% (10.3-12.2), decreased after 3 months to 8.7% (8.2 - 11.1) (p <0.05), to 6 months to 8 months, 3% (8.0-9.6) (p <0.05), at 12 months it rose 9.0% (5.9-14.5) (p <0.001) and at 18 months 9.0 % (5.9-14.6) (p <0.001). The dose of degludec was 0.5 U / kg / weight at 18 months. There was reduction of hypoglycemia: at 3 months, 14 mild, 4 moderate, 1 severe; at 6 months 8 mild, 2 moderate and none serious; at 12 months 1 mild, and at 18 months 2 mild, 1 moderate and none serious. 7.8% did not present hypoglycemia. Conclusion: Degludec in T1D patients showed to reduce fasting glycemia and HbA1c, and lower number of hypoglycemia.

Experiencia con insulina degludec en pacientes diabéticos Tipo 1 del Hospital San Juan de Dios Santiago / Experience with degludec insulin in Type 1 diabetic patients at the San Juan de Dios Hospital

OBJECTIVE: To study the efficacy and safety of degludec insulin in Type 1 diabetic patients. PATIENTS AND METHOD: In a prospective study, 230 type 1 diabetics patients, average aged 34 years age and 14 years of diagnosis of diabetes and treated with two doses of insulin glargine U-100, were changed to degludec. Patients had glycosylated hemoglobins (HbA1c) greater than 10 percent. Results were recorded at 3 and 6 months with parameters clinical, biochemical, insulin requirements per kilogram of weight (U/kg/wt) and hypoglycemia. Capillary glycemia was evaluated three times a day and the dose of insulin degludec every two weeks. The statistical analysis used was average and rank, standard deviation, normal Swilk test, categorical Chi2 and continuous ANOVA or Kwallis, and p < 0.05. A psychological survey was conducted to evaluate satisfaction with the new treatment. RESULTS: Fasting blood glucose decreased from 253 (range 243-270) at 180 mg/dl (172-240) at 3 months and at 156 (137-180) at 6 months after the change insulin (p < 0.05). HbA1c, initially 10.6 percent (10.4-12.2) decreased to 8.7 percent (9.3-10.1) and 8.3 percent (8.7-9.7) at 3 and 6 months, respectively (p < 0.05). There was a decrease in basal insulin requirements from 0.7 to 0.4 U/kg/60 percent reduction in hypoglycaemia; both mild and moderate and severe. Isolated nocturnal hypoglycaemias were recorded in only 4 patients in this group. CONCLUSION: Six months of treatment with degludec insulin reduces fasting blood glucose, glycosylated hemoglobin and hypoglycemia, both mild and moderate severe and nocturnal, which makes this new ultra-long acting basal insulin a safe and effective tool for the management of type 1 diabetics patients

Practical Focus on American Diabetes Association/European Association for the Study of Diabetes Consensus Algorithm in Patients with Type 2 Diabetes Mellitus: Timely Insulin Initiation and Titration (Iran-AFECT)

BACKGROUND: The aim of this study was to evaluate the safety and effectiveness of insulin glargine in a large population from a variety of clinical care in Iranian people with type 2 diabetes mellitus (T2DM) and to measure the percentage of patients achieving glycosylated hemoglobin (HbA1c) <7% by the end of 24 weeks of treatment in routine clinical practice. METHODS: This study was a 24 week, observational study of patients with T2DM, for whom the physician had decided to initiate or to switch to insulin glargine. The safety and efficacy of glargine were assessed at baseline and at week 24. RESULTS: Seven hundred and twenty-five people with T2DM (63% female) including both insulin naïve and prior insulin users were recruited in this study. The mean age of the participants was 54.2±11.2 years, and the mean HbA1c level was 8.88%±0.93% at baseline. By the end of the study, 27% of the entire participants reached to HbA1c target of less than 7% and 52% had HbA1c ≤7.5%. No serious adverse event was reported in this study. Furthermore, overall hypoglycemia did not increase in prior insulin users and the entire cohort. In addition, body weight did not change in participants while lipid profile improved significantly. CONCLUSION: Treatment with insulin glargine could improve glycemic control without increasing the risk of hypoglycemic events in people with T2DM. In addition, a significant clinical improvement was observed in lipid profile.

Exenatide versus Insulin Lispro Added to Basal Insulin in a Subgroup of Korean Patients with Type 2 Diabetes Mellitus

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) and obesity is increasing in Korea. Clinical studies in patients with T2DM have shown that combining the glucagon-like peptide-1 receptor agonist exenatide twice daily with basal insulin is an effective glucose-lowering strategy. However, these studies were predominantly conducted in non-Asian populations. METHODS: We conducted a subgroup analysis of data from a multinational, 30-week, randomized, open-label trial to compare the effects of exenatide twice daily (n=10) or three times daily mealtime insulin lispro (n=13) among Korean patients with T2DM inadequately controlled (glycosylated hemoglobin [HbA1c] >7.0%) on metformin plus optimized insulin glargine. RESULTS: Exenatide twice daily and insulin lispro both reduced HbA1c (mean −1.5% and −1.0%, respectively; P<0.01 vs. baseline). Fasting glucose and weight numerically decreased with exenatide twice daily (−0.7 mmol/L and −0.7 kg, respectively) and numerically increased with insulin lispro (0.9 mmol/L and 1.0 kg, respectively). Minor hypoglycemia occurred in four patients receiving exenatide twice daily and three patients receiving insulin lispro. Gastrointestinal adverse events were the most common with exenatide twice daily treatment. CONCLUSION: This analysis found treatment with exenatide twice daily improved glycemic control without weight gain in Korean patients with T2DM unable to achieve glycemic control on metformin plus basal insulin.

Effectiveness of glargine insulin on recovery of patients with diabetic ketoacidosis

Background: Diabetic Ketoacidosis [DKA] is one of emergency conditions caused by acute hyperglycemia in diabetic patients. The main treatment is injection of rapid-acting Regular insulin. This study was aimed to investigate the effect of Glargine insulin on recovery of patients with DKA

Methods: A randomized clinical trial [RCT] conducted on 40 patients [twenty patients in each group] with DKA. Both groups received standard treatment regimen for DKA. In addition, the experimental group was given 0.4 U/kg of insulin glargine

Results: The mean duration of acidosis correction time and recovery from DKA was 13.77+/-6.10 hours in the case group and 16.91+/-6.49 hours in control group [p=0.123]. The mean dosage of regular insulin until recovery from DKA was 84.8+/-45.6 units in the case group and 116.5+/-91.6 units in control group [p=0.17]. Hypokalemia [p=l] and hypoglycemia [p=l] were not different between two groups. In 35% of samples in case group and 51% in controls, the blood sugar [BS] was more than 180 mg/dl for 24 hours after discontinuation of the insulin infusion [pFO.046]. The mean duration of hospitalization was 5.1+/-1.88 days in case and 5.9+/-2.19 days in control group [p=0.225]

Conclusion: Adding insulin Glargine to the standard treatment regimen of DKA significantly reduced rebound hyperglycemia without incurring episodes of hypoglycemia and hypokalemia

It also reduced the average time of recovery from DKA, regular insulin consumption and hospital length, although these changes were not statistically significant. It seems that the non-significant difference be related to the paucity of sample size and close monitoring of patients

Predetermined Anti-Diabetic Drug Regimen Adjustments during Ramadan Fasting: An Observational Study of Safety

BACKGROUND: Many Muslim type 2 diabetes mellitus (T2DM) patients choose to fast the month of Ramadan despite the possible adverse health effects brought about by the change in dietary habits, among other things. Clinical data regarding the safety of multi-drug regimens during fasting are particularly scarce. The aim of the study was to evaluate the safety of a drug protocol devised by the authors to accommodate Ramadan's dietary changes, involving dose adjustments of four anti-diabetic drug regimens in T2DM patients fasting Ramadan. METHODS: In this prospective, observational, open-label study, 301 T2DM patients who wished to fast Ramadan were followed during Ramadan and the preceding month. The incidence of hypoglycemia, diabetic ketoacidosis (DKA) and non-ketotic hyperosmolar state (NKHS) was monitored. Patients were classified into four groups: A group (those taking metformin, sulfonylurea and insulin [n=33]); B group (metformin and sulfonylurea [n=89]); C group (metformin and insulin [n=96]); and D group (premixed 70/30, glargine or regular insulin [n=82]). During Ramadan, drug doses were adjusted as percentages of their pre-Ramadan values: 75% for sulfonylureas, 75% for glargine, 75% for premixed insulin 70/30 in two doses, and 75% for regular insulin. Metformin was adjusted to a twice-daily regimen. RESULTS: No cases of DKA or NKHS were reported. Hypoglycemia occurred at a lower rate than pre-Ramadan values in groups C, and D; and a similar rate in groups A, and B. CONCLUSION: The data suggested that using the above protocol to adjust the doses of anti-diabetic drugs is safe in T2DM patients in regards to hypoglycemia, DKA, and NKHS.

Análisis comparativo de insulina glargina frente a la insulina detemir: un modelo de minimización de costos aplicable en Colombia / Comparative analysis of insulin glargine vs. insulin detemir: A cost-minimization study applicable to Colombia

Introducción. Más del 90 % de los individuos diagnosticados con diabetes mellitus presentan el tipo 2, cuya resistencia periférica a la acción de la insulina es conocida. Objetivo. Desarrollar un modelo de minimización de costos del tratamiento con insulina glargina una vez al día o con insulina detemir, una o dos veces al día, en pacientes con diabetes mellitus de tipo 2 que requieren insulina, desde la perspectiva del tercer pagador en Colombia. Materiales y métodos. Se hizo una búsqueda sistemática de estudios clínicos comparativos de la administración de insulina glargina e insulina detemir en pacientes con diabetes mellitus de tipo 2 que requieren insulina, con el fin de extraer los datos sobre su uso y efectividad, y sobre la frecuencia de eventos secundarios. La meta establecida de control glucémico fue de HbA1c=7 %. Los costos de la insulina se tomaron del Sistema Integrado de Precios de Medicamentos, 2012, del Ministerio de Salud y Protección Social, y los precios por tableta se basaron en el promedio móvil de doce meses en diciembre de 2012 según el IMS Consulting Group. Los análisis de sensibilidad se hicieron con simulaciones de Montecarlo para las dosis y los costos de la insulina. Resultados. Cinco publicaciones cumplieron con los criterios de inclusión. El rango de la diferencia entre dosis de insulina fue de 3,2 a 33 UI. El porcentaje de pacientes que requirieron dos dosis de insulina detemir estuvo entre 12,6 y 100 %. No hubo diferencias significativas en los eventos hipoglucémicos. Tanto para el canal de compra al por menor como para el de compras institucionales, la diferencia de costos entre la insulin glargina y la detemir favoreció a la primera en cuatro y cinco estudios, respectivamente. Solo un estudio mostró lo contrario en lo concerniente a la venta al por menor. Conclusiones. La diferencia en cuanto a la dosis promedio entre la insulina ganglir y la detemir, genera costos anuales que favorecen el uso de la insulina ganglir, lo que la convierte en una alternativa costo-efectiva frente a la determir.

Introduction: More than 90% of subjects diagnosed with diabetes mellitus present with type 2, which is recognized for peripheral insulin resistance. Objective: To determine the costs of achieving glycemic target with the use of basal insulin analogs, insulin glargine (IG) once a day vs. insulin detemir (ID) once or twice a day, with a cost minimization model built from a third-party payer perspective in Colombia. Materials and methods: A systematic review of comparative clinical trials between IG and ID in patients with insulin-resistant type 2 diabetes was performed to determine data of use, effectiveness and frequency of and adverse events. The goal of glycemic control (effectiveness measure) was defined as HbA1c=7%. The costs of insulin were extracted from the Integrated System of Medication Prices 2012 (Ministerio de Salud y Protección Social de Colombia) and the IMS Consulting Group mobile average cost for the past year as of December, 2012. Sensitivity analyses were performed via Montecarlo simulations for dose and medication costs (insulin). Results: Five publications met inclusion criteria. The range of the difference between insulin doses was 3.2 IU to 33 IU. The percentage of patients requiring two ID doses was 12.6-100%. There were no significant differences in hypoglycemic events. For both retail and institutional channels, there was a higher differential cost between IG vs. ID favoring IG in 4 and 5 studies, respectively. For the retail channel only one study showed the opposite results. Conclusions: As only medication costs are considered, differences in insulin units between IG and ID result in a differential cost in favor of IG that makes it a cost/effective alternative.

Clinical Use of New Insulins and New Insulin Delivery Systems / 임상당뇨병

Insulin plays an important role in the treatment of diabetes. Since it was discovered in the early 1920s, major advances have been made in the medical use of insulin. However, certain insulin associated challenges remain, such as hypoglycemia, weight gain, complex management, and injection site pain. Novel insulins and delivery systems are being developed that can address these limitations. Insulin degludec is a novel basal insulin with a long half-life (25 hours) and action duration (> 42 hours). Glargine U300 is a concentrated formulation of insulin glargine. For improvement in postprandial glucose control, ultrarapid-acting insulins are being investigated. New insulin delivery systems including inhaled insulin and insulin patches are also being developed to overcome the inconvenience associated with subcutaneous injection. In this review, clinical studies of new insulins and new insulin delivery systems are summarized.

Insulinas análogas de longa ação Diabetes Mellitus tipo II / Analog Long-acting Insulins Type II Diabetes Mellitus

A DOENÇA: Diabetes Mellitus (DM), de acordo com a Organização Mundial da Saúde (OMS), é o termo que descreve uma desordem metabólica de etiologia múltipla, caracterizada por hiperglicemia crônica e distúrbios no metabolismo de carboidratos, lipídios e proteínas resultantes de defeitos na secreção de insulina, na ação da insulina ou em ambos. Para a Sociedade Brasileira de Diabetes (SDB), a classificação atual do DM deve levar em conta a sua etiologia. Assim, convergente com associações internacionais e com a própria OMS, a Diabetes Mellitus é classificada em quatro classes clínicas: DM tipo 1, DM tipo 2, outros tipos específicos de DM e DM gestacional. O diabetes tipo 2 (DM2) é a forma mais presente destas manifestações, atingindo mais de 90% dos casos e caracteriza-se por defeitos na ação e secreção de insulina. Desenvolve-se geralmente em adultos e tem sido relacionada à obesidade, falta de atividade física e hábitos alimentares não saudáveis. TRATAMENTO: No tratamento do diabetes tipo 2, é recomendado um plano terapêutico que vise o controle glicêmico e a prevenção de complicações crônicas decorrentes da doença. Para isso, este plano deve englobar não apenas o tratamento farmacológico, mas medidas que conduzam à mudança de estilo vida, com orientação nutricional e atividade física, pois existem comprovadas evidências do impacto do tratamento não farmacológico na melhoria de parâmetros importantes para a doença, como redução da hemoglobina glicada, sensibilidade à insulina, diminuição do colesterol, perda de peso e gordura visceral, diminuição do risco de doença cardiovascular e melhora da qualidade de vida. Em relação ao tratamento farmacológico, atualmente está disponível no SUS para o tratamento da DM2 as insulinas de ação intermediária (insulina NPH) e de ação rápida (insulina regular), além de medicamentos hipoglicemiantes (biguanidas, derivados da uréia, sulfonamidas). A TECNOLOGIA: Insulinas análogas de longa ação: As insulinas análogas de longa ação são resultantes de mudanças estruturais na molécula de insulina humana, obtida a partir da tecnologia do DNA-recombinante, com o objetivo de estender a duração do efeito e diminuir a variação intra-individual. São consideradas alternativas terapêuticas para o controle glicêmico basal, possuindo o mesmo objetivo da insulina NPH. EVIDÊNCIAS CIENTÍFICAS: A Secretaria-Executiva da CONITEC realizou busca na literatura por artigos científicos, com o objetivo de localizar a melhor evidência científica disponível sobre o tema. Considerando o grande número de publicações sobre o tema, restringiram-se os resultados apenas às revisões sistemáticas disponíveis, entendendo que esta é a melhor evidência para avaliar a eficácia de uma tecnologia para tratamento. A busca por evidências sobre a eficácia das insulinas glargina e detemir em comparação à insulina NPH no controle do DM2 foi realizada nas bases de dados MEDLINE (via Pubmed), Cochrane Library (via Bireme) e Centre for Reviews and Dissemination. CONSIDERAÇÕES FINAIS: A evidência atualmente disponível sobre eficácia e segurança das insulinas análogas de longa ação (glargina e detemir) no tratamento do diabetes mellitus tipo 2 não mostrou que esta fosse superior à insulina NPH em relação ao controle glicêmico medido pela hemoglobina glicosilada (HbA1c), glicemia em jejum, redução da hipoglicemia severa e presença de efeitos adversos (segurança). No que diz respeito à menor ocorrência de hipoglicemia noturna, os resultados tendem a favorecer as insulinas análogas, mas deve-se avaliar o real benefício clínico frente à diferença aferida nos estudos. Deve-se, também, considerar as limitações metodológicas dos estudos, como a avaliação subjetiva e as diferentes definições para o episódio de hipoglicemia, o desenho aberto dos estudos, o potencial conflito de interesse de alguns autores e estudos patrocinados pelo produtor farmacêutico. Além disso, o curto período de seguimento dos estudos impede a mensuração de efeitos primordiais (morbidade, mortalidade, complicações em longo prazo), impossibilitando a medida da real relevância clínica das insulinas análogas de longa ação em relação ao tratamento convencional (insulina NPH). Assim, observa-se que a literatura científica internacional aponta na direção de que não há evidências de que as insulinas análogas trazem melhoras significativas nas condições de saúde dos pacientes e que o benefício clínico associado ao uso das insulinas análogas é ainda discreto frente aos custos relacionados ao tratamento. As insulinas análogas de longa ação (detemir e glargina) parecem não ser inferiores à insulina humana NPH, mas também não está claro se apresentariam alguma superioridade em benefício clínico. O impacto orçamentário também se apresentou como um obstáculo na incorporação destas insulinas análogas, quando consideramos o grande aporte de recursos necessários para a sua introdução e o seu benefício clínico incerto frente à insulina NPH. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na 24ª reunião ordinária do plenário do dia 09/04/2014, por unanimidade, ratificaram a deliberação de não recomendar a incorporação das insulinas análogas de longa ação (detemir e glargina) para o tratamento do Diabetes Mellitus tipo II. DECISÃO: PORTARIA Nº 30, de 4 de setembro de 2014 - Torna pública a decisão de não incorporar as insulinas análogas para diabetes mellitus tipo II no âmbito do Sistema Único de Saúde - SUS.

MEK1 and MEK2 differentially regulate human insulin- and insulin glargine-induced human bladder cancer T24 cell proliferation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Increased risk of bladder cancer has been reported in diabetic patients. This study was to investigate the roles of mitogen-activated protein kinase kinase (MEK) 1 and 2 in the regulation of human insulin- and insulin glargine-induced proliferation of human bladder cancer T24 cells.</p><p><b>METHODS</b>In the absence or presence of a selective inhibitor for MEK1 (PD98059) or a specific siRNA for MEK2 (siMEK2), with or without addition of insulin or glargine, T24 cell proliferation was evaluated by cell counting kit (CCK)-8 assay. Protein expression of MEK2, phosphorylation of ERK1/2 and Akt was analyzed by Western blotting.</p><p><b>RESULTS</b>T24 cell proliferation was promoted by PD98059 at 5 - 20 µmol/L, inhibited by siMEK2 at 25 - 100 nmol/L. PD98059 and siMEK2 remarkably reduced phosphorylated ERK1/2. Insulin- and glargine-induced T24 cell proliferation was enhanced by PD98059, suppressed while not blocked by siMEK2. Insulin- and glargine-induced ERK1/2 activation was blocked by PD98059 or siMEK2 treatment, whereas activation of Akt was not affected.</p><p><b>CONCLUSION</b>MEK1 inhibits while MEK2 contributes to normal and human insulin- and insulin glargine-induced human bladder cancer T24 cell proliferation.</p>

Application of an Insulin Analogue in Six Hypoglycemia-Prone Hemodialysis Patients with Type 2 Diabetes / 대한내과학회지

Day-to-day insulin requirements often change due to subtle variations in insulin metabolism in patients with type 2 diabetes undergoing hemodialysis. In such cases, intra-hemodialysis hypoglycemia frequently occurs and is a main factor interfering with the delivery of dialysis. As a result, it reduces the quality of life in patients undergoing hemodialysis. The long-acting insulin analogue glargine provides peakless, continuous release over 24 h that approximates a normal basal insulin pattern. Because it has no peak, its use in patients with diabetes undergoing hemodialysis would hypothetically be useful. Specifically, patients would be able to avoid intra-hemodialysis hypoglycemia without the necessity of skipping insulin administration on the day of hemodialysis and achieving adequate glucose control on other days. We recently experienced six cases that switched from treatment with intermediate-acting insulin to a long-acting insulin analogue, which provided better glycemic control by reducing hypoglycemia risk. Limited data are available in the literature concerning insulin analogue usage in patients with diabetes undergoing hemodialysis. Our experience suggests a large-scale prospective investigation is required on this issue.

Glycemic Effects of Once-a-Day Rapid-Acting Insulin Analogue Addition on a Basal Insulin Analogue in Korean Subjects with Poorly Controlled Type 2 Diabetes Mellitus

BACKGROUND: The present study investigates the efficacy in glycemic control by adding once-a-day glulisine to glargine as a basal plus regimen and factors influencing glycemic control with the basal plus regimen in Korean subjects with type 2 diabetes. METHODS: In the present retrospective study, subjects previously treated with the basal plus regimens for at least 6 months were reviewed. Changes in glycemic profiles and clinical parameters were evaluated. RESULTS: A total of 87 subjects were ultimately enrolled in this study. At baseline, mean glycated hemoglobin (A1c) and glycated albumin were 8.5% (8.0% to 9.6%) and 25.2+/-7.6%, respectively. After treatment with the basal plus regimen, patients had significant reductions of A1c at 6 months (0.8+/-0.1%, P<0.001) and their postprandial glucose levels were decreased by 48.7+/-10.3 mg/dL (P<0.001). Multiple logistic regression showed old age (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02 to 1.55), high initial A1c (OR, 22.21; 95% CI, 2.44 to 201.78), and lower amounts of glargine (OR, 0.85; 95% CI, 0.76 to 0.99), and glimepiride (OR, 0.23; 95% CI, 0.06 to 0.93) at baseline were independently associated with good responders whose A1c reduction was more than 0.5%. CONCLUSION: The authors suggest a basal plus regimen may be effective in reducing glucose levels of subjects with old age, high initial A1c, and patients on low doses of glimepiride and glargine. Despite the use of high doses of hypoglycemic agents, elderly patients with poorly-controlled diabetes are preferred for early initiation of the basal plus regimen.

Efficacy and safety evaluation of two insulin treatment protocols using a continuous glucose monitoring system / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of two insulin treatment protocols using a continuous glucose monitoring system.</p><p><b>METHODS</b>Type 2 diabetic patients mellitus with unsatisfactory control of fasting blood glucose by oral antidiabetic drugs were included in the study. The patients were randomized into two groups to receive bedtime injection of glargine and oral antidiabetic drugs (group A) or injection of Novolin 30 R twice a day (group B) for 12 weeks. The insuline dose was adjusted according to fasting blood glucose till discharge. Continuous glucose monitoring system was used to record the average blood glucose, fasting blood glucose, 2 h postprandial blood glucose, AUCPG ≥ 10.0 mmol/L%, HbA1c and C peptide, bedtime blood glucose, 3:00 AM blood glucose, the incidence of hypoglycemia and body mass index.</p><p><b>RESULTS</b>The average blood glucose, fasting blood glucose, 2 h postprandial blood glucose, AUCPG ≥ 10.0 mmol/L% and HbA1c was significantly decreased and C peptide significantly increased in the two groups after the treatments. The patients in glargine group showed better improvement with a significantly lower incidence of hypoglycemia than those in Novolin 30 R group. BMI underwent no significant changes in the two groups after the treatments.</p><p><b>CONCLUSION</b>Glargine therapy better mimics the physiological insulin secretion patterns, and when combined with oral antidiabetic drugs, can be more effective and safer than premixed insulin.</p>