[Pharmacological and clinical characteristics of Insulin Faster Aspart (Fiasp®)]. / Características farmacológicas y clínicas de Insulina Aspártica Más Rápida (Fiasp®).

Fast acting aspart insulin is a faster-acting formulation of aspart insulin, having nicotinamide and Larginine added to the molecule, in order to achieve a faster absorption through the subcutaneous cellular tissue. Pharmacokinetic and pharmacodynamic studies showed a left-shifted mean serum concentration-time profile compared to the conventional formulation. Its efficacy profile is highlighted in terms of early postprandial glycemic control. In addition, fast acting aspart insulin allows a more flexible treatment schedule, as it may be administrated at mealtime, immediately before or up to 20 minutes after; this schedule represents an advantage regarding quality of life in patients with diabetes treated with prandial insulin, especially in populations such as children, pregnant women or elderly subjects. The safety and tolerability profiles are comparable to conventional aspart insulin.

La insulina aspártica de acción rápida es una formulación más rápida de la insulina aspártica convencional, a la que se adicionan nicotinamida y L-arginina para lograr una absorción más rápida en el tejido celular subcutáneo. Estudios farmacocinéticos y farmacodinámicos demostraron un desplazamiento de las curvas de concentración sérica de insulina/tiempo hacia la izquierda en comparación con la formulación convencional. Su perfil de eficacia se destaca en términos del control de la glucemia posprandial temprana. Además, la insulina aspártica de acción rápida aporta flexibilidad al tratamiento, ya que puede aplicarse al momento de la comida, inmediatamente antes o hasta 20 minutos después, lo que constituye una ventaja en cuanto a calidad de vida en los pacientes con diabetes en tratamiento con insulina prandial, especialmente en poblaciones como los niños, las embarazadas o los ancianos. El patrón de seguridad y tolerabilidad es comparable al de la insulina aspártica convencional.

Características farmacológicas y clínicas de insulina aspártica más rápida (Fiasp®) / Pharmacological and clinical characteristics of Insulin Faster Aspart (Fiasp®)

Resumen La insulina aspártica de acción rápida es una formulación más rápida de la insulina aspártica convencional, a la que se adicionan nicotinamida y L-arginina para lograr una absorción más rápida en el tejido celular subcutáneo. Estudios farmacocinéticos y farmacodinámicos demostraron un desplazamiento de las curvas de concentración sérica de insulina/tiempo hacia la izquierda en comparación con la formulación conven cional. Su perfil de eficacia se destaca en términos del control de la glucemia posprandial temprana. Además, la insulina aspártica de acción rápida aporta flexibilidad al tratamiento, ya que puede aplicarse al momento de la comida, inmediatamente antes o hasta 20 minutos después, lo que constituye una ventaja en cuanto a calidad de vida en los pacientes con diabetes en tratamiento con insulina prandial, especialmente en poblaciones como los niños, las embarazadas o los ancianos. El patrón de seguridad y tolerabilidad es comparable al de la insulina aspártica convencional.

Abstract Fast acting aspart insulin is a faster-acting formulation of aspart insulin, having nicotinamide and L-arginine added to the molecule, in order to achieve a faster absorption through the subcutaneous cellular tissue. Pharmacokinetic and pharmacodynamic studies showed a left-shifted mean serum concentration-time profile compared to the conventional formulation. Its efficacy profile is highlighted in terms of early postprandial glycemic control. In addition, fast acting aspart insulin allows a more flexible treatment schedule, as it may be administrated at mealtime, immediately before or up to 20 minutes after; this schedule represents an advantage regarding quality of life in patients with diabetes treated with prandial insulin, especially in populations such as children, pregnant women or elderly subjects. The safety and tolerability profiles are comparable to conventional aspart insulin.

Effect of ultra-rapid insulin aspart on glycemic control in children with type 1 diabetes: the experience of a Portuguese tertiary centre.

Background: Postprandial hyperglycemia is one of the biggest challenges in children with type 1 diabetes (T1D). Ultra-fast-acting aspartic insulin (faster aspart) has a quicker onset of action and an earlier maximum activity. The aim of this study is to analyze the impact of faster aspart in metabolic control of pediatric patients with T1D in a "real-world" setting. Methods: Retrospective analysis of 60 pediatric patients with T1D who changed their insulin analogue to faster aspart. Anthropometric data, insulin doses, capillary and interstitial glucose recordings and average glycated hemoglobin before and after insulin analogue's switch were obtained. After all population analyses, patients were analyzed separately according to the type of treatment, multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII), and according to age group. Results: Faster aspart significantly improved metabolic control, increasing time in range (TIR) (42 vs.54%, respectively; P = 0.007) and decreasing time above range (TAR) (52 vs.40%, respectively; P = 0.009), without an increased time in hypoglycemia (7% before and after faster aspart's introduction; P = 0.933). This was reassured in the adolescent years (n = 45), with an increase in TIR (37 vs. 47%, respectively; P = 0.034) and decrease in TAR (51 vs. 45%, respectively; P = 0.022). Patients on CSII (n = 47), also demonstrated an increase in TIR (38 vs. 50%, respectively; P = 0.010). The reduction of A1c was not statistically significant. Conclusion: Although the advantage of faster aspart had already been demonstrated in pediatric patients under MDI, "real-world" studies, including patients under CSII, are still lacking. This study highlights the important impact of faster aspart on metabolic control in children with T1D, particularly among adolescents under CSII.

Impacto de faster aspart sobre el control glucémico en niños y adolescentes con diabetes tipo 1 en tratamiento con un sistema integrado / The impact of «faster aspart» on blood glucose control in children and adolescents with type 1 diabetes treated using a sensor-augmented insulin pump

Introducción y objetivos: El control glucémico postprandial es fundamental para conseguir los objetivos metabólicos en pacientes con diabetes mellitus tipo 1 (DM1). La nueva insulina faster aspart presenta un perfil farmacológico caracterizado por una absorción e inicio de acción más rápidos, mayor disponibilidad precoz y menor incremento de la glucosa postprandial. El objetivo principal del estudio fue analizar su eficacia en pacientes con DM1 tratados con un sistema integrado.Pacientes y métodos: Estudio analítico, longitudinal, prospectivo y multicéntrico, evaluando el empleo de faster aspart durante tres meses en pacientes en edad pediátrica con DM1 con sistema integrado MiniMed640G® tratados previamente con insulina aspart. Al inicio y final del estudio se analizaron para posterior comparación: glucosa media, porcentajes de tiempo en objetivo, tiempo en hipoglucemia e hiperglucemia, área bajo la curva (AUC) < 70 y > 180 mg/dL, glucosa media pre y postprandial en comidas principales, necesidades diarias de insulina, porcentaje basal/bolo y HbA1c. Se registraron complicaciones agudas y eventos adversos, y se evaluó grado de satisfacción mediante encuesta.Resultados: Se incluyeron 31 pacientes de 13,49 ± 2,42 años de edad con DM1 de 7,0 ± 3,67 años de evolución. Faster aspart se asoció con menor porcentaje de tiempo en hiperglucemia > 180 mg/dL (25,8 ± 11,3 vs. 22,4 ± 9,5; p = 0,011) y > 250 mg/dL (5,2 ± 4,9 vs. 4,0 ± 3,6; p = 0,04) y AUC > 180 mg/dL (10,8 ± 6,5 vs. 9,3 ± 6,1; p = 0,03), incrementándose el tiempo en objetivo (71,4 ± 10,0 vs. 74,3 ± 9,2; p = 0,03) sin aumentar hipoglucemias. Las necesidades de insulina, porcentajes basal/bolo y HbA1c no se modificaron significativamente. Faster aspart fue bien tolerada y valorada por los participantes.Conclusiones: Faster aspart consigue un mejor control glucémico, aumentando el tiempo de glucosa en objetivo en niños y adolescentes con DM1 en tratamiento con un sistema integrado. (AU)

Background and aims: Post-prandial glucose control is essential to achieve metabolic goals in patients with type 1 diabetes mellitus (T1DM). The new «faster aspart» insulin has a pharmacological profile noted for its faster absorption and onset of action, and increased early availability, resulting in improved blood glucose control after meals. The main objective of the study was to analyse the efficacy of «faster aspart» vs. «insulin aspart» in children and adolescents with DM1 on sensor-augmented pump treatment.Patients and methods: Multicentre, longitudinal and prospective analytical trial evaluating the use of faster aspart insulin for three months in children with T1DM with MiniMed640G® sensor-augmented pumps previously treated with aspart insulin. At the beginning and end of the study the following variables were analysed for subsequent comparison: mean sensor glucose, percentage of time in range, hypoglycaemia and hyperglycaemia, area under the curve (AUC) < 70 and > 180 mg/dL, mean sensor glucose pre and postprandial in main meals, daily insulin requirements, basal/bolus percentage, and HbA1c. Acute complications, adverse events and satisfaction survey were assessed.Results: The study included 31 patients with a mean of 13.49 ± 2.42 years of age and with T1DM of 7.0 ± 3.67 years of onset. The use of faster aspart was associated with lower time in hyperglycaemia > 180 mg/dL (25.8 ± 11.3 vs. 22.4 ± 9.5; p = 0.011) and > 250 mg/dL (5.2 ± 4.9 vs. 4.0 ± 3.6; p = 0.04), lower AUC > 180 mg/dL (10.8 ± 6.5 vs. 9.3 ± 6.1; p = 0.03), and increased time in range (71.4 ± 10.0 vs. 74.3 ± 9.2; p = 0.03). No significant changes in hypoglycaemia, HbA1c, insulin requirements, and basal/bolus percentages were detected. Faster aspart was safe and well-evaluated by patients and caregivers.Conclusions: Faster aspart achieves better glycaemic control by increasing glucose time in range in children and adolescents with T1DM on treatment with sensor-augmented pumps. (AU)

The impact of "faster aspart" on blood glucose control in children and adolescents with type 1 diabetes treated using a sensor-augmented insulin pump.

BACKGROUND AND AIMS: Post-prandial glucose control is essential to achieve metabolic goals in patients with type 1 diabetes mellitus (T1DM). The new "faster aspart" insulin has a pharmacological profile noted for its faster absorption and onset of action, and increased early availability, resulting in improved blood glucose control after meals. The main objective of the study was to analyse the efficacy of "faster aspart" vs. "insulin aspart" in children and adolescents with DM1 on sensor-augmented pump treatment. PATIENTS AND METHODS: Multicentre, longitudinal and prospective analytical trial evaluating the use of faster aspart insulin for three months in children with T1DM with MiniMed640G® sensor-augmented pumps previously treated with aspart insulin. At the beginning and end of the study the following variables were analysed for subsequent comparison: mean sensor glucose, percentage of time in range, hypoglycaemia and hyperglycaemia, area under the curve (AUC) <70 and >180 mg/dL, mean sensor glucose pre- and postprandial in main meals, daily insulin requirements, basal/bolus percentage, and HbA1c. Acute complications, adverse events and satisfaction survey were assessed. RESULTS: The study included 32 patients with a mean of 13.49 ± 2.42 years of age and with T1DM of 7.0 ± 3.67 years of onset. The use of faster aspart was associated with lower time in hyperglycaemia >180 mg/dL (25.8 ± 11.3 vs. 22.4 ± 9.5; p = .011) and >250 mg/dL (5.2±4.9 vs. 4.0 ± 3.6; p = .04), lower AUC >180 mg/dL (10.8 ± 6.5 vs. 9.3 ± 6.1; p = .03), and increased time in range (71.4 ± 10.0 vs. 74.3 ± 9.2; p = .03). No significant changes in hypoglycaemia, HbA1c, insulin requirements, and basal/bolus percentages were detected. Faster aspart was safe and well-evaluated by patients and caregivers. CONCLUSIONS: Faster aspart achieves better glycaemic control by increasing glucose time in range in children and adolescents with T1DM on treatment with sensor-augmented pumps.

Metformin for gestational diabetes study: metformin vs insulin in gestational diabetes: glycemic control and obstetrical and perinatal outcomes: randomized prospective trial.

BACKGROUND: Gestational diabetes that is not properly controlled with diet has been commonly treated with insulin. In recent years, several studies have published that metformin can lead to, at least, similar obstetrical and perinatal outcomes as insulin. Nevertheless, not all clinical guidelines endorse its use, and clinical practice is heterogeneous. OBJECTIVE: This study aimed to test whether metformin could achieve the same glycemic control as insulin and similar obstetrical and perinatal results, with a good safety profile, in women with gestational diabetes that is not properly controlled with lifestyle changes. STUDY DESIGN: The metformin for gestational diabetes study was a multicenter, open-label, parallel arms, randomized clinical trial performed at 2 hospitals in Málaga (Spain), enrolling women with gestational diabetes who needed pharmacologic treatment. Women at the age of 18 to 45 years, in the second or third trimesters of pregnancy, were randomized to receive metformin or insulin (detemir or aspart). The main outcomes were (1) glycemic control (mean glycemia, preprandial and postprandial) and hypoglycemic episodes and (2) obstetrical and perinatal outcomes and complications (hypertensive disorders, type of labor, prematurity, macrosomia, large for gestational age, neonatal care unit admissions, respiratory distress syndrome, hypoglycemia, jaundice). Outcomes were analyzed on an intention-to-treat basis. RESULTS: Between October 2016 and June 2019, 200 women were randomized, 100 to the insulin-treated group and 100 to the metformin-treated group. Mean fasting and postprandial glycemia did not differ between groups, but postprandial glycemia was significantly better after lunch or dinner in the metformin-treated-group. Hypoglycemic episodes were significantly more common in the insulin-treated group (55.9% vs 17.7% on metformin; odds ratio, 6.118; 95% confidence interval, 3.134-11.944; P=.000). Women treated with metformin gained less weight from the enrollment to the prepartum visit (36-37 gestational weeks) (1.35±3.21 vs 3.87±3.50 kg; P=.000). Labor inductions (45.7% [metformin] vs 62.5% [insulin]; odds ratio, 0.506; 95% confidence interval, 0.283-0.903; P=.029) and cesarean deliveries (27.6% [metformin] vs 52.6% [insulin]; odds ratio, 0.345; 95% confidence interval, 0.187-0.625; P=.001) were significantly lower in the metformin-treated group. Mean birthweight, macrosomia, and large for gestational age and babies' complications were not different between treatment groups. The lower cesarean delivery rate for women treated with metformin was not associated with macrosomia, large or small for gestational age, or other complications of pregnancy. CONCLUSION: Metformin treatment was associated with a better postprandial glycemic control than insulin for some meals, a lower risk of hypoglycemic episodes, less maternal weight gain, and a low rate of failure as an isolated treatment. Most obstetrical and perinatal outcomes were similar between groups.

[The impact of «faster aspart¼ on blood glucose control in children and adolescents with type 1 diabetes treated using a sensor-augmented insulin pump]. / Impacto de faster aspart sobre el control glucémico en niños y adolescentes con diabetes tipo 1 en tratamiento con un sistema integrado.

BACKGROUND AND AIMS: Post-prandial glucose control is essential to achieve metabolic goals in patients with type 1 diabetes mellitus (T1DM). The new «faster aspart¼ insulin has a pharmacological profile noted for its faster absorption and onset of action, and increased early availability, resulting in improved blood glucose control after meals. The main objective of the study was to analyse the efficacy of «faster aspart¼ vs. «insulin aspart¼ in children and adolescents with DM1 on sensor-augmented pump treatment. PATIENTS AND METHODS: Multicentre, longitudinal and prospective analytical trial evaluating the use of faster aspart insulin for three months in children with T1DM with MiniMed640G® sensor-augmented pumps previously treated with aspart insulin. At the beginning and end of the study the following variables were analysed for subsequent comparison: mean sensor glucose, percentage of time in range, hypoglycaemia and hyperglycaemia, area under the curve (AUC) < 70 and > 180 mg/dL, mean sensor glucose pre and postprandial in main meals, daily insulin requirements, basal/bolus percentage, and HbA1c. Acute complications, adverse events and satisfaction survey were assessed. RESULTS: The study included 31 patients with a mean of 13.49 ± 2.42 years of age and with T1DM of 7.0 ± 3.67 years of onset. The use of faster aspart was associated with lower time in hyperglycaemia > 180 mg/dL (25.8 ± 11.3 vs. 22.4 ± 9.5; p = 0.011) and > 250 mg/dL (5.2 ± 4.9 vs. 4.0 ± 3.6; p = 0.04), lower AUC > 180 mg/dL (10.8 ± 6.5 vs. 9.3 ± 6.1; p = 0.03), and increased time in range (71.4 ± 10.0 vs. 74.3 ± 9.2; p = 0.03). No significant changes in hypoglycaemia, HbA1c, insulin requirements, and basal/bolus percentages were detected. Faster aspart was safe and well-evaluated by patients and caregivers. CONCLUSIONS: Faster aspart achieves better glycaemic control by increasing glucose time in range in children and adolescents with T1DM on treatment with sensor-augmented pumps.

Short-acting insulin analogues versus regular human insulin on postprandial glucose and hypoglycemia in type 1 diabetes mellitus: a systematic review and meta-analysis.

INTRODUCTION: Strict glucose control using multiple doses of insulin is the standard treatment for type 1 diabetes mellitus (T1DM), but increased risk of hypoglycemia is a frequent drawback. Regular insulin in multiple doses is important for achieving strict glycemic control for T1DM, but short-acting insulin analogues may be better in reducing hypoglycemia and postprandial glucose levels. OBJECTIVE: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effects of short-acting insulin analogues vs regular human insulin on hypoglycemia and postprandial glucose in patients with T1DM. METHODS: Searches were run on the electronic databases MEDLINE, Cochrane-CENTRAL, EMBASE, ClinicalTrials.gov, LILACS, and DARE for RCTs published until August 2017. To be included in the study, the RCTs had to cover a minimum period of 4 weeks and had to assess the effects of short-acting insulin analogues vs regular human insulin on hypoglycemia and postprandial glucose levels in patients with T1DM. Two independent reviewers extracted the data and assessed the quality of the selected studies. The primary outcomes analyzed were hypoglycemia (total episodes, nocturnal hypoglycemia, and severe hypoglycemia) and postprandial glucose (at all times, after breakfast, after lunch, and after dinner). Glycated hemoglobin (HbA1c) levels and quality of life were considered secondary outcomes. The risk of bias of each RCT was assessed using the Cochrane Collaboration Risk of Bias table, while the quality of evidence for each outcome was assessed using the GRADEpro software. The pooled mean difference in the number of hypoglycemic episodes and postprandial glucose between short-acting insulin analogues vs. regular human insulin was calculated using the random-effects model. RESULTS: Of the 2897 articles retrieved, 22 (6235 patients) were included. Short-acting insulin analogues were associated with a decrease in total hypoglycemic episodes (risk rate 0.93, 95% CI 0.87-0.99; 6235 patients; I2 = 81%), nocturnal hypoglycemia (risk rate 0.55, 95% CI 0.40-0.76, 1995 patients, I2 = 84%), and severe hypoglycemia (risk rate 0.68, 95% CI 0.60-0.77; 5945 patients, I2 = 0%); and with lower postprandial glucose levels (mean difference/MD - 19.44 mg/dL; 95% CI - 21.49 to - 17.39; 5031 patients, I2 = 69%) and lower HbA1c (MD - 0,13%; IC 95% - 0.16 to - 0.10; 5204 patients; I2 = 73%) levels. CONCLUSIONS: Short-acting insulin analogues are superior to regular human insulin in T1DM patients for the following outcomes: total hypoglycemic episodes, nocturnal hypoglycemia, severe hypoglycemia, postprandial glucose, and HbA1c.

[Faster aspart insulin (FIASP®)]. / Le médicament du mois. L'insuline «faster aspart¼ (Fiasp®).

Fast-acting insulin aspart (faster aspart), commercialized under the trade name of Fiasp®, is insulin aspart in a new formulation aiming to mimic the physiologic prandial insulin release more closely than currently available rapid-acting insulin products. Fiasp® is insulin aspart (NovoRapid®) in which two excipients (L-arginine and niacinamide) have been added, L-arginine serving as a stabilising agent, while niacinamide being responsible for accelerated initial absorption after subcutaneous administration. The pharmacokinetic characteristics of insulin faster aspart have the potential to better reproduce the fast endogenous prandial insulin secretion and thereby to improve postprandial glucose control compared with insulin aspart. The onset phase 3 programme compares head-to-head insulin faster aspart to insulin aspart. Studies showed significant reductions in postprandial glucose increment (in type 1 and type 2 diabetic patients), and glycated haemoglobin (HbA1C, in type 1 diabetes), without markedly increasing the risk of hypoglycaemia. A post hoc analysis of pooled data from six clinical trials conducted in patients with type 1 diabetes confirmed the beneficial pharmacokinetic and pharmacodynamic profiles of insulin faster aspart (earlier plasma insulin appearance, early insulin exposure two times greater and earlier offset of exposure of insulin faster aspart versus insulin aspart).

L'insuline aspart ultra-rapide («faster aspart¼), commercialisée sous le nom de Fiasp®, est de l'insuline aspart modifiée dans le but de reproduire, de manière plus proche que ne le font les préparations d'insuline à action rapide actuellement disponibles, la sécrétion physiologique prandiale d'insuline. Fiasp® est constituée d'insuline aspart (commercialisée sous le nom de Novorapid®) à laquelle deux excipients (L-arginine et nicotinamide) ont été ajoutés, la L-arginine comme agent stabilisateur de la préparation et la nicotinamide pour favoriser une absorption initiale accélérée après administration sous-cutanée. Les caractéristiques pharmacocinétiques de l'insuline faster aspart présentent le potentiel de mieux mimer la sécrétion précoce d'insuline qui suit le repas et, de ce fait, de contrôler, de manière plus efficace, l'hyperglycémie postprandiale en comparaison à ce que l'on observe avec de l'insuline aspart. Le programme onset d'études cliniques de phase 3 vise à comparer directement l'insuline faster aspart à l'insuline aspart. Ces études ont démontré une réduction significative des augmentations de la glycémie postprandiale (chez les sujets diabétiques de type 1 et de type 2) et de l'hémoglobine glyquée (HbA1C, dans le diabète de type 1), sans augmenter sensiblement le risque d'hypoglycémie. Une analyse post hoc de données rassemblées à partir de six études cliniques réalisées dans le diabète de type 1 a confirmé le bénéfice du profil pharmacocinétique et pharmacodynamique de l'insuline faster aspart par rapport à l'insuline aspart (apparition plasmatique plus précoce de l'insuline et exposition initiale à l'insuline deux fois plus importante, avec une durée d'exposition raccourcie).

[Insulinization in type 2 diabetes mellitus. Intensification options]. / Insulinización en la diabetes mellitus tipo 2. Alternativas de intensificación.

Diabetes mellitus is associated with vascular complications and high rates of morbidity and mortality. Timely insulin therapy, intensified when necessary, represent appropriate measures to prevent or delay the onset of complications. However, the incidence of hypoglycemia and difficulties in treatment adherence represent barriers to achieve therapeutic success. Premixes analogs and, specially, combinations of insulin analogues are associated with pharmacokinetic and pharmacodynamic advantages, that translate into clinical benefits such as improved metabolic control, decreased hypoglycemic events and, for their simplicity, potentially greater adherence.

Insulinización en la diabetes mellitus tipo 2: Alternativas de intensificación / Insulinization in type 2 diabetes mellitus. Intensification options

La diabetes mellitus se asocia con complicaciones vasculares y elevadas tasas de morbimortalidad. La terapia oportuna con insulina y su intensificación cuando es necesaria, representan estrategias apropiadas para evitar o retardar la aparición de dichas complicaciones. Sin embargo, la incidencia de hipoglucemia y las dificultades en la adherencia al tratamiento representan barreras para alcanzar el éxito terapéutico. Las nuevas combinaciones de análogos de insulina constituyen tratamientos que presentarían ventajas farmacocinéticas y farmacodinámicas, logrando beneficios clínicos tales como un mejor control metabólico, la disminución de eventos hipoglucémicos y, por su simplicidad, potencialmente una mayor adherencia al tratamiento.

Diabetes mellitus is associated with vascular complications and high rates of morbidity and mortality. Timely insulin therapy, intensified when necessary, represent appropriate measures to prevent or delay the onset of complications. However, the incidence of hypoglycemia and difficulties in treatment adherence represent barriers to achieve therapeutic success. Premixes analogs and, specially, combinations of insulin analogues are associated with pharmacokinetic and pharmacodynamic advantages, that translate into clinical benefits such as improved metabolic control, decreased hypoglycemic events and, for their simplicity, potentially greater adherence.

Rheological properties of regular insulin and aspart insulin Langmuir monolayers at the air/water interface: condensing effect of Zn2+ in the subphase.

The interfacial behavior of regular insulin (Reg-insulin) and aspart insulin (Asp-insulin) was critically affected by the presence of Zn(2+) in the subphase. This cation induced a condensed-like behavior in the compression isotherms, especially apparent for Reg-insulin films when observed by Brewster angle microscopy. Immediately after spreading, Reg-insulin, but not Asp-insulin, showed bright patches that moved in a gaseous-like state. Moreover, Zn(2+) caused marked variations of the surface electrostatics of both insulin monolayers and considerable hysteresis of their molecular organization. By oscillatory compression-expansion cycles, we observed in all cases the development of a dilatational response to the surface perturbation, and both monolayers exhibited well-defined shear moduli in the presence of Zn(2+), which was higher for Reg-insulin. Development of a shear modulus indicates behavior resembling a nominal solid, more apparent for Reg-insulin than for Asp-insulin, suggesting the presence of viscoelastic networks at the surface.

Efficacy and safety of biphasic insulin aspart 30/70 in type 2 diabetes suboptimally controlled on oral antidiabetic therapy in Korea: a multicenter, open-label, single-arm study.

BACKGROUND: The purpose of this study was to evaluate change in glycosylated hemoglobin (HbA1c), side effects, and quality of life (QOL) after a 16-week treatment period with Biphasic insulin aspart 30/70 (BIasp30) in patients with type 2 diabetes mellitus (T2DM) who had been suboptimally controlled with oral antidiabetic drugs (OADs). METHODS: The study consisted of a 4-week titration period when concurrent OAD(s) were replaced with BIasp30 and followed by a 12-week maintenance period. All patients completed the Diabetes Treatment Satisfaction Questionnaire at the beginning and the end of the trial. Hypoglycemic episodes were recorded by the patient throughout the trial. RESULTS: Sixty patients were included, of whom 55 patients (92%) completed the full 16-week treatment period. Seven-point blood glucose was significantly improved as compared with the baseline, except for the postlunch blood glucose level. HbA1c at the end of period was significantly improved from 9.2% to 8.2% (P<0.001). Eleven percent (n=6) of patients achieved HbA1c values ≤6.5% and 22% (n=12) of patients achieved <7.0%. There were 3.4 episodes/patients-year of minor hypoglycemia and 0.05 episodes/patients-year of major hypoglycemia. QOL showed significant changes only in the acceptability of high blood glucose category (P=0.003). CONCLUSION: Treatment with once or twice daily BIasp30 may be an option for the patients with T2DM suboptimally controlled with OADs in Korea. However, considering the low number of patients achieving the HbA1c target and the high postlunch blood glucose levels, additional management with another modality may be required for optimal control.

Efficacy and Safety of Biphasic Insulin Aspart 30/70 in Type 2 Diabetes Suboptimally Controlled on Oral Antidiabetic Therapy in Korea: A Multicenter, Open-Label, Single-Arm Study

BACKGROUND: The purpose of this study was to evaluate change in glycosylated hemoglobin (HbA1c), side effects, and quality of life (QOL) after a 16-week treatment period with Biphasic insulin aspart 30/70 (BIasp30) in patients with type 2 diabetes mellitus (T2DM) who had been suboptimally controlled with oral antidiabetic drugs (OADs). METHODS: The study consisted of a 4-week titration period when concurrent OAD(s) were replaced with BIasp30 and followed by a 12-week maintenance period. All patients completed the Diabetes Treatment Satisfaction Questionnaire at the beginning and the end of the trial. Hypoglycemic episodes were recorded by the patient throughout the trial. RESULTS: Sixty patients were included, of whom 55 patients (92%) completed the full 16-week treatment period. Seven-point blood glucose was significantly improved as compared with the baseline, except for the postlunch blood glucose level. HbA1c at the end of period was significantly improved from 9.2% to 8.2% (P<0.001). Eleven percent (n=6) of patients achieved HbA1c values < or =6.5% and 22% (n=12) of patients achieved <7.0%. There were 3.4 episodes/patients-year of minor hypoglycemia and 0.05 episodes/patients-year of major hypoglycemia. QOL showed significant changes only in the acceptability of high blood glucose category (P=0.003). CONCLUSION: Treatment with once or twice daily BIasp30 may be an option for the patients with T2DM suboptimally controlled with OADs in Korea. However, considering the low number of patients achieving the HbA1c target and the high postlunch blood glucose levels, additional management with another modality may be required for optimal control.