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1.
Orv Hetil ; 161(5): 193-197, 2020 Feb.
Artigo em Húngaro | MEDLINE | ID: mdl-31984772

RESUMO

Mortality in type 1 diabetes, although showing a declining trend, is significantly higher than standard mortality. The case study focuses on a woman who lived for 91 years; she was insulin-dependent for 86 years and has been treated by a single physician - the author - for over 55 years. She was diagnosed with diabetes in 1932 at the age of five. Her diabetes was first treated with rapid-acting insulin three times daily, then from 1940 with rapid-acting and protamine zinc insulin once daily, while later on pork, then human crystalline zinc insulin was used, followed by a mixture of rapid-acting and NPH insulin for the last 16 years. The reason behind the above treatment regimen was that the patient obsessively insisted on a once daily insulin dose and the duration was shown to be 24 hours for each insulin. The continuous overdose of a single insulin for decades has resulted in hypoglycemic episodes almost daily, with consequent high fluctuations in blood glucose levels. She performed urine glucose tests using a polarimeter from the mid-1930s to the sixties, then used test strips until the early eighties, and later switched to blood glucose self-testing. Her HbA1c levels have been around 7% (53 mmol/mol) for the last 25 years. She did not develop retinopathy or nephropathy, only severe neuropathy caused complaints during the last years of her life. In addition, her vision continued to deteriorate due to age-related dry macular degeneration. She is a Joslin 75-year medalist. For the last two months of her life, she gave permission for degludec + glulisine insulin intensive treatment. Her death was caused by myocardial infarction. Although minimizing blood glucose fluctuations and sustaining good metabolic control significantly improve the life expectancy of people with diabetes, in our case neither has existed for well over half a century. Therefore, no explanation was found for the extremely long duration of diabetes and longevity. Orv Hetil. 2020; 161(5): 193-197.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Infarto do Miocárdio/mortalidade , Idoso de 80 Anos ou mais , Glicemia , Evolução Fatal , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Insulina , Insulina Glargina/administração & dosagem , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Infarto do Miocárdio/complicações , Resultado do Tratamento
3.
Medicina (B Aires) ; 79(4): 241-250, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31487242

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina Glargina/administração & dosagem , Insulina Glargina/farmacocinética , Medicina Baseada em Evidências , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacocinética , Insulina Glargina/efeitos adversos
4.
Acta Diabetol ; 56(12): 1283-1292, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31407113

RESUMO

AIMS: Subcutaneous administration of insulin in patients suffering from diabetes is associated with the distress of daily injections. Among alternative administration routes, the oral route seems to be the most advantageous for long-term administration, also because the peptide undergoes a hepatic first-pass effect, contributing to the inhibition of the hepatic glucose output. Unfortunately, insulin oral administration has so far been hampered by degradation by gastrointestinal enzymes and poor intestinal absorption. Loading in lipid nanoparticles should allow to overcome these limitations. METHODS: Entrapment of peptides into such nanoparticles is not easy, because of their high molecular weight, hydrophilicity and thermo-sensitivity. In this study, this objective was achieved by employing fatty acid coacervation method: solid lipid nanoparticles and newly engineered nanostructured lipid carriers were formulated. Insulin and insulin analog-glargine insulin-were entrapped in the lipid matrix through hydrophobic ion pairing. RESULTS: Bioactivity of lipid entrapped peptides was demonstrated through a suitable in vivo experiment. Ex vivo and in vivo studies were carried out by employing fluorescently labelled peptides. Gut tied up experiments showed the superiority of glargine insulin-loaded nanostructured lipid carriers, which demonstrated significantly higher permeation (till 30% dose/mL) compared to free peptide. Approximately 6% absolute bioavailability in the bloodstream was estimated for the same formulation through in vivo pharmacokinetic studies in rats. Consequently, a discrete blood glucose responsivity was noted in healthy animals. CONCLUSIONS: Given the optimized ex vivo and in vivo intestinal uptake of glargine insulin from nanostructured lipid carriers, further studies will be carried out on healthy and diabetic rat models in order to establish a glargine insulin dose-glucose response relation.


Assuntos
Portadores de Fármacos , Insulina/administração & dosagem , Lipídeos , Nanopartículas , Administração Oral , Animais , Células Cultivadas , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Humanos , Insulina/análogos & derivados , Insulina/farmacocinética , Insulina Glargina/administração & dosagem , Insulina Glargina/análogos & derivados , Insulina Glargina/farmacocinética , Lipídeos/administração & dosagem , Lipídeos/química , Lipídeos/farmacocinética , Masculino , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/metabolismo , Técnicas de Cultura de Órgãos , Tamanho da Partícula , Ratos , Ratos Wistar
5.
Endocr J ; 66(8): 745-752, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31308304

RESUMO

To examine the efficacy and safety of once-daily insulin degludec/insulin aspart (IDegAsp) or once-daily second-generation basal insulin analogs (insulin degludec and insulin glargine 300 units/mL) in insulin-naïve Japanese adults with type 2 diabetes in routine clinical practice. A 12-week multicenter, open-label, randomized, pilot study was performed in 52 subjects with type 2 diabetes treated with oral antidiabetic drugs (OADs). Subjects were randomized to once-daily IDegAsp (n = 26) or basal insulin (n = 26). The primary endpoint was percent change in HbA1c from baseline to week 12. Furthermore, it was analyzed post hoc in subgroups stratified by baseline HbA1c. During a follow-up period, percent change in HbA1c was not significantly different between the two groups (p = 0.161). Daily insulin doses and frequency of overall hypoglycemia were also similar in the two groups. In post hoc analyses, once-daily basal insulin was more effective than IDegAsp in subjects with HbA1c more than or equal to 8.5% (p < 0.05); however, in subjects with HbA1c less than 8.5%, once-daily IDegAsp showed a significant improvement in percent change in HbA1c at week 12, compared with basal insulin (p < 0.01). Although there was no apparent difference in the HbA1c-lowering effects between two groups, when compared in subjects with HbA1c less than 8.5%, once-daily IDegAsp showed a significant effect in comparison with once-daily basal insulin. These findings suggest that the baseline HbA1c level might provide the important information for choosing IDegAsp or basal insulin in patients insufficiently controlled with OADs. This trial was registered with UMIN (no. UMIN000035431).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina Glargina/administração & dosagem , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/efeitos adversos , Administração Oral , Adulto , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Preparações de Ação Retardada , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Combinação de Medicamentos , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Projetos Piloto
6.
Aten. prim. (Barc., Ed. impr.) ; 51(6): 350-358, jun.-jul. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-185715

RESUMO

Objetivos: Evaluar el impacto de una estrategia de intervención en el patrón de prescripción de la insulina glargina biosimilar (IGBio) respecto al compuesto de referencia y analizar la influencia del perfil del prescriptor y su repercusión económica. Diseño: Estudio cuasiexperimental de tipo antes/después, con un grupo control. Emplazamiento: Dos áreas de gestión sanitaria (AGS) de Sevilla: AGS Sur (área intervención) y AGS Osuna (área control). Participantes: La totalidad de los médicos de atención primaria de cada área: 220 y 100, respectivamente. Intervención: Se realizaron sesiones formativas, se envió un boletín farmacoterapéutico e informes de retroalimentación mensual durante los 6meses tras la intervención formativa. El estudio fue llevado a cabo desde la comercialización del biosimilar, en octubre de 2015, hasta febrero de 2016 (pre-intervención) y desde febrero hasta agosto de 2016 (intervención). Mediciones principales: Los indicadores analizados han sido porcentaje de pacientes y porcentaje de dosis diaria definida (DDD) con IGBio respecto al total y el coste. Los médicos han sido analizados por subgrupos de edad, sexo, formación, tipo de contrato, años de experiencia y cupo. Resultados principales: Ambos indicadores aumentan al mismo nivel en ambas áreas antes de la intervención. Sin embargo, después de la intervención fueron significativamente diferentes entre las áreas (p < 0,0005), intervalo de confianza al 95% (2,5-4,7). La razón del porcentaje de incremento relativo acumulado de ambas variables entre áreas fue 3,73 veces mayor tras la intervención. En el área intervención no se encontraron diferencias para los subgrupos de médicos evaluados. Conclusiones: Estrategias encaminadas a la formación/información, así como el seguimiento a los profesionales sanitarios, inciden en el patrón de prescripción y pueden tener una repercusión económica. Nuestros resultados no se han visto influenciados por el perfil del prescriptor


Objectives: To examine the effects of specific interventions on biosimilar glargine insulin (BGI) prescribing in general practices and to analyse the influence of prescriber and economic impact. Design: Non randomized controlled study. Setting: General practices in 2 health areas of Seville, intervention and control group. Participants: 220 general practices (intervention group) and 100 general practices (control group). Intervention: Intervention group received educational seminars on biosimilar drugs, pharmacotherapeutic bulletin and prescribing feedback. The study was carried out from the biosimilar commercialization, October-2015, to February-2016 (pre-intervention) and from February to August 2016 (intervention). Main measurements: Percentage of patients and DDD with BGI respect to total glargine before and during intervention for both areas were analysed. Physicians have been analysed by subgroups of age, sex, training, type of contract, years of experience and quota. Main results: Both indicators for intervention group were significantly greater than for control group (P < .0005), with a 95% confidence interval (2.5-4.7). The ratio of the percentage of cumulative increase of both variables between areas was 3.73 times higher after the intervention. No differences were found for the evaluated categories of physicians in the intervention group. Conclusions: Intervention strategies aimed at training and information, as well as monitoring health professionals, influence the pattern of prescription and can have an economic impact. Our results have not been influenced by the profile of the prescriber


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estratégias , Resultado do Tratamento , Prescrições de Medicamentos/normas , Insulina Glargina/normas , Atenção Primária à Saúde , Medicamentos Biossimilares/uso terapêutico , Insulina Glargina/administração & dosagem , Prescrições de Medicamentos/economia , Diabetes Mellitus/tratamento farmacológico
7.
Intern Med ; 58(20): 2943-2948, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31243228

RESUMO

Objective We compared the pain accompanying the injection of high-concentration (300 units/mL) insulin glargine (U300G) with that accompanying the injection of conventional (100 units/mL) insulin glargine (U100G). Methods U100G was switched to U300G at basically the same dosage. Visual analog scales were used to assess the quality of life (QOL). The primary outcome was the change in the pain accompanying injections in those using ≥30 units of U100G compared with those using <30 units at baseline. Standardized mean differences (Cohen's d) were used to measure the effect size. Patients Adult patients with type 2 diabetes mellitus using U100G. Results One hundred and eight patients were recruited. The numbers of patients who used U100G at ≥30 units, 20 to <30 units, 10 to <20 units, and <10 units were 13, 14, 34, and 47, respectively. The improvement in the pain score was not significant for ≥30 units compared with <30 units (-50.3±24.0 vs. -40.4±28.5, p=0.25, d=0.38), but a significant difference was observed for ≥20 units compared with <20 units (-50.8±22.7 vs. -38.4±29.1, p=0.03, d=0.48), as well as for ≥10 units compared with <10 units (-48.1±25.0 vs. -33.0±29.7, p<0.01, d=0.56). When all patients were analyzed together, significant improvements in the pain score (-41.5±28.0, p<0.01), ease of use score (-37.5±32.2, p<0.01), force needed to inject score (-46.5±28.6, p<0.01), and preference for U300G compared with U100G score (-45.8±33.1, p<0.01) were observed. Conclusion There is possibility that switching from U100G to U300G might be associated with better QOL for patients who require insulin glargine injections. To prove this hypothesis, a randomized controlled trial (preferably double-blinded) will be required in the future.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina Glargina/administração & dosagem , Dor/etiologia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Composição de Medicamentos , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Injeções Subcutâneas/efeitos adversos , Insulina Glargina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Preferência do Paciente , Psicometria
8.
Diabetes Res Clin Pract ; 152: 58-64, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31102682

RESUMO

AIM: To report glycemic control and pregnancy outcome in pregnant women with type 1 diabetes on insulin degludec. METHODS: Twenty-two women with type 1 diabetes on degludec from conception to delivery between 2014 and 2018 were compared with 51 pregnant women with type 1 diabetes on glargine. RESULTS: Baseline characteristics were comparable, however HbA1c was higher at median 9 (range 5-19) weeks in women on degludec compared to women on glargine (6.9% (5.7-8.7); (52 (39-72) mmol/mol) versus 6.4% (5.1-10.1); (46 (32-87) mmol/mol), p = 0.04). HbA1c was similar in late pregnancy (6.3% (5.6-7.1); (45 (38-54) mmol/mol) versus 6.1% (5.2-9.0); (43 (33-75) mmol/mol), p = 0.28). The prevalence of severe hypoglycemia was 3 (14%) versus 6 (12%), p = 1.00 during pregnancy and 0 versus 1, p = 1.00 during hospital admittance after delivery. Most women on degludec used one daily injection in early (20 (91%) versus 25 (49%), p = 0.001) and late pregnancy (21 (96%) versus 19 (37%), p < 0.001). No significant differences in obstetrical and neonatal outcomes were found between the groups. Maternal hospital admittance after delivery was 2 (1-5) versus 3 (2-11) days (p = 0.004). CONCLUSIONS: Glycemic control in late pregnancy, severe hypoglycemia during and immediately after pregnancy as well as pregnancy outcome were comparable in women on degludec or glargine. Degludec initiated preconceptionally may be continued in pregnancy.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina de Ação Prolongada/administração & dosagem , Gravidez em Diabéticas/tratamento farmacológico , Adulto , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/metabolismo , Hospitalização/estatística & dados numéricos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina Glargina/administração & dosagem , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez/epidemiologia , Gravidez em Diabéticas/sangue , Gravidez em Diabéticas/epidemiologia , Prevalência , Resultado do Tratamento , Adulto Jovem
9.
Nutr Metab Cardiovasc Dis ; 29(5): 496-503, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30952575

RESUMO

BACKGROUND AND AIMS: Fostering patient's self-managing of basal insulin therapy could improve glucose control, by removing patient's and physician's barriers to basal insulin initiation, titration and glucose monitoring. The Italian Titration Approaches Study (ITAS) aims at demonstrating non-inferiority (<0.3% margin) in efficacy of glucose control (change in glycated hemoglobin [HbA1c] after 24 weeks) by the same titration algorithm of insulin glargine 300 U/mL (Gla-300), managed by the (nurse assisted) patient versus the physician, in insulin naïve patients with Type 2 Diabetes Mellitus (T2DM), uncontrolled with previous treatments. METHODS AND RESULTS: ITAS is a phase IV, 24-week, national, multicenter, open label, randomized (1:1) parallel group study. 458 patients were enrolled, 359 randomized, and 339 completed the study, in 46 Italian centers. Baseline characteristics and previous medications of the ITT population (N = 355) are reported. Mean ± SD age, T2DM duration, HbA1c, FPG and BMI were 64.0 ± 9.8 years, 11.6 ± 7.6 years, 8.79 ± 0.65%, 170.9 ± 42.3 mg/dL, and 30.3 ± 5.6 kg/m2, respectively. Vascular and metabolic disorders were most frequent (73.8% and 58.3%, respectively). More than 90% of patients were on metformin. CONCLUSION: ITAS is the first study to compare two different managers (nurse-assisted patient vs physician) of the same titration algorithm of Gla-300 in insulin naïve patients with T2DM in unsatisfactory glucose control. This study might provide novel evidence on the efficacy/effectiveness of patient-managed titration algorithm of Gla-300 in a pragmatic setting and may reduce barriers to basal insulin initiation and its titration.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina Glargina/administração & dosagem , Autocuidado , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/enfermagem , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Itália , Masculino , Pessoa de Meia-Idade , Papel do Profissional de Enfermagem , Participação do Paciente , Papel do Médico , Fatores de Tempo , Resultado do Tratamento
10.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(4): 210-216, abr. 2019. graf
Artigo em Espanhol | IBECS | ID: ibc-183170

RESUMO

Introducción: Los tratamientos insulínicos actuales para diabetes tipo 1 (DM1) no siempre consiguen los objetivos de control metabólico debido, entre otros aspectos, a la aparición de episodios de hipoglucemia asociados al uso de insulina. Material y métodos: Estudio descriptivo en la vida real con 247 pacientes DM1, el 55,5% varones, de 46,53 ± 16,23 años, con un tiempo de evolución de 21,89 ± 11,99 años, a los que se sustituyó su insulina basal, glargina U100, por glargina U300. Los objetivos primarios fueron los cambios en la HbA1c y en el número de hipoglucemias y los secundarios fueron los cambios en el peso y en la dosis de insulina trascurridos 6 y 12 meses. Resultados: Tras un año, no se observaron cambios en la HbA1c en el total de los pacientes, si bien se comprobó un descenso significativo en los pacientes mal controlados. Sin embargo, aumentó el porcentaje de pacientes con HbA1c < 7,5% a los 6 meses (33,5 vs. 40,5%; p < 0,05), que se mantuvo al año. El número de hipoglucemias leves se redujo tras los 12 meses de tratamiento en aquellos pacientes con antecedentes de hipoglucemias leves. En cuanto al peso, no observamos cambios. La dosis total de insulina/kg se incrementó significativamente en un 7,24% a los 6 meses y en un 8,69% al año por el aumento de la insulina basal. Las diferencias en las dosis a los 6 meses y al año no fueron significativas. Este aumento fue similar entre los grupos según el control metabólico, la presencia de hipoglucemias y no se relacionó con la insulina basal inicial, la HbA1c inicial, el número de hipoglucemias leves ni con el peso inicial. Discusión: En la vida real glargina U300 muestra un mejor control glucémico en pacientes mal controlados, al reducir las hipoglucemias en pacientes con antecedentes de hipoglucemias sin incrementar el peso corporal


Introduction: Current treatment of type 1 diabetes mellitus (T1DM) does not always achieve metabolic control because, among other things, the ocurrence of hypoglycemic events associated to insulin use. Material and methods: A descriptive real life study of 247 T1DM patients, 55.5% male, aged 46.53 ± 16.23 years, and with a mean diabetes duration of 21.89 ± 11.99 years, who were switched from basal insulin glargine U100 to glargine U300. The primary endpoints were changes in Hba1c and number of hypoglycemic events, while secondary endpoints included changes in weight and insulin dose after 6 and 12 months. Results: After one year, no changes were seen in HbA1c, but the proportion of patients with HbA1c values <7.5% increased at 6 months (33.5 vs. 40.5%; P<0.05) and remained stable during one year of follow-up. Hypoglycemic events significantly decreased after one year of treatment in patients with previous hypoglycemic events. No changes were seen in body weight. Total insulin dose (U/kg) increased 7.24% at 6 months of treatment and by 8.69% at one year, mainly due to basal insulin. No changes were seen between the doses given at 6 and 12 months. These changes were similar in the different metabolic control groups and in patients with or without hypoglycemia. This increase was not related with prior basal insulin dose, baseline HbA1c level, number of hypoglycemic events or baseline weight. Discussion: Glargine U300 is a good basal insulin alternative to treat T1DM, improving metabolic control in patients with HbA1c levels >7,5 and decreasing hypoglycemic events in patients with history of hypoglycemia without increasing body weight


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina Glargina/administração & dosagem , Hipoglicemiantes/administração & dosagem , Estudos Retrospectivos , Peso Corporal/efeitos da radiação , Resultado do Tratamento , Seguimentos
11.
Drugs ; 79(2): 173-186, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30623349

RESUMO

The recent introduction of the second-generation long-acting analogue insulins degludec and insulin glargine U300 have increased the choice of basal insulin therapy for patients with type 2 diabetes. The pharmacokinetic and pharmacodynamic properties of these insulins result in a flatter profile that lasts over 24 h and provides an increased window of administration of 6 h once daily. Large-scale multicentre randomised clinical trial programmes (BEGIN for degludec U100 and U200 and EDITION for glargine U300) evaluating these insulin therapies against glargine U100 have demonstrated that they are either non-inferior or superior for glycaemic efficacy and safety, but less likely to result in severe or nocturnal hypoglycaemia than glargine U100. The disposable pen devices for these insulins have been designed with patient satisfaction and convenience in mind. No concerns have arisen with adverse events with insulin analogues or cardiovascular safety from the ORIGIN and DEVOTE trials. As they demonstrate equivalent glycaemic efficacy to other basal insulins, they should be considered more in selected patient groups including those with recurrent or increased risk of hypoglycaemia, especially severe or nocturnal episodes, in the elderly or those living alone, and in patients with multiple co-morbidities such as cardiovascular or renal disease.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Glicemia , Esquema de Medicação , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina Glargina/administração & dosagem , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/efeitos adversos , Resultado do Tratamento
12.
Med. clín (Ed. impr.) ; 152(1): 19-21, ene. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-181669

RESUMO

Introducción: La diabetes tipo MODY engloba un grupo heterogéneo de formas monogénicas de diabetes de baja prevalencia. Pacientes y métodos: Presentamos un caso clínico con clínica cardinal, diabetes e insuficiencia renal sin acidosis, con antecedentes familiares de diabetes y padre monorreno. Resultados: Dado el aumento de obesidad y antecedentes familiares de diabetes en la población general, su sospecha diagnóstica no resulta fácil. Distinguir diabetes tipo MODY de DM1 y DM2 es crucial ya que el tratamiento óptimo y el riesgo de complicaciones varía con el defecto genético subyacente. Discusión: Un adecuado diagnóstico precisa de una historia clínica orientada y detallada, permitiendo una identificación más temprana de los miembros en riesgo de la familia y adecuar el tratamiento, ya que muchos de estos pacientes pueden ser tratados con éxito en monoterapia retirando la insulinoterapia innecesaria


Introduction: MODY diabetes encompasses heterogeneous group of monogenic forms of diabetes with low prevalence. It is not easily diagnosed because of the increase in obesity and family history of diabetes in the general population. Patients and methods: We present a clinical case with cardinal symptoms, diabetes,renal insufficiency with no acidosis and with a family history of diabetes and renal agenesis. Results: Distinguishing MODY diabetes from DM1 and DM2 is very important to ensure optimal treatment, and because the risk of complications depends on each genetic defect. A proper diagnosis needs a detailed medical history. Discussion: An earlier identification of family members at risk and a correct and individualised treatment could be possible. Many of these patients can be managed successfully in monotherapy without insulin therapy


Assuntos
Humanos , Masculino , Adulto , Rim Único/epidemiologia , Diabetes Mellitus/etiologia , Obesidade/epidemiologia , Insulina Glargina/administração & dosagem , Rim Único/complicações , Diabetes Mellitus/genética , Obesidade/complicações , Índice Glicêmico , Diagnóstico Diferencial
13.
Diabetes Obes Metab ; 21(2): 234-243, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30129089

RESUMO

AIM: To compare the efficacy and safety of once-weekly dulaglutide with that of insulin glargine in combination with metformin and/or a sulphonylurea in mainly Asian patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: In this 52-week, randomized, parallel-arm open-label study, we enrolled patients aged ≥18 years with T2DM for at least 6 months and a glycated haemoglobin (HbA1c) concentration ≥53.0 mmol/mol (7.0%) and ≤96.7 mmol/mol (11.0%). The primary outcome was change in HbA1c from baseline to week 26 to determine non-inferiority of dulaglutide 1.5 mg versus glargine. RESULTS: A total of 774 patients from China, South Korea, Mexico and Russia were randomly assigned (1:1:1) to dulaglutide 1.5 mg, dulaglutide 0.75 mg or glargine treatment groups. The patients' mean age was 55 years and the average T2DM duration was ~8 years. The least squares mean (SE) changes from baseline in HbA1c at 26 weeks were - 18.9 (0.73) mmol/mol (-1.73 [0.067]%) for dulaglutide 1.5 mg and -14.5 (0.73) mmol/mol (-1.33 [0.067]%) for dulaglutide 0.75 mg, compared with -12.7 (0.73) mmol/mol (-1.16 [0.067]%) for glargine. Statistical criteria for superiority were met with both dulaglutide 1.5 mg and dulaglutide 0.75 mg. More patients in the dulaglutide 1.5 and 0.75 mg groups achieved HbA1c target <53.0 mmol/mol (<7.0%) than in the glargine group at week 26 (P < 0.001 and P = 0.004, respectively). Body weight decreased with dulaglutide and increased with glargine. The incidence and rate of total hypoglycaemia were lower with dulaglutide versus glargine. Gastrointestinal adverse events, including diarrhoea and nausea, were the most frequently reported for patients taking dulaglutide. CONCLUSIONS: Once-weekly dulaglutide provides greater improvement in HbA1c, with weight loss and less hypoglycaemia, than once-daily insulin glargine in a population of mainly Asian patients with T2DM who had failed to achieve optimal glycaemic control on metformin and/or a sulphonylurea.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Insulina Glargina/administração & dosagem , Metformina/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Compostos de Sulfonilureia/administração & dosagem , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , China/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Esquema de Medicação , Quimioterapia Combinada , Feminino , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/metabolismo , Humanos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Insulina Glargina/efeitos adversos , Masculino , Metformina/efeitos adversos , México/epidemiologia , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/efeitos adversos , República da Coreia/epidemiologia , Federação Russa/epidemiologia , Compostos de Sulfonilureia/efeitos adversos , Resultado do Tratamento
14.
Diabetes Obes Metab ; 21(2): 402-407, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30160030

RESUMO

The EDITION trials in type 2 diabetes demonstrated comparable glycaemic control with less nocturnal and anytime (24-hour) hypoglycaemia for insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100). However, the predefined nocturnal window (0:00-5:59 AM) may not be the most relevant for clinical practice. This post-hoc analysis compared expansions of the predefined nocturnal interval during basal insulin treatment without prandial insulin. Patient-level, 6-month data, pooled from the EDITION 2 and 3 trials and the EDITION JP 2 trial (N = 1922, basal insulin only) were analysed. Accompanying hypoglycaemia during treatment with Gla-300 was compared to that during treatment with Gla-100, using predefined (0:00-5:59 AM) and expanded (10:00 PM-5:59 AM, 0:00-7:59 AM, 10:00 PM to pre-breakfast SMPG) windows. Confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events were reported most frequently between 6:00 AM and 8:00 AM. Windows expanded beyond 6:00 AM included more events than other windows. The percentage of participants with at least one event was lower with Gla-300 than Gla-100 in all windows examined. Expanding the nocturnal interval allows better assessment of the risk of hypoglycaemia associated with basal insulin. The risk of nocturnal hypoglycaemia was consistently lower with Gla-300 versus Gla-100 using all four windows.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Insulina Glargina/administração & dosagem , Insulina Glargina/efeitos adversos , Insulina/administração & dosagem , Adulto , Ritmo Circadiano/efeitos dos fármacos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Insulina/efeitos adversos , Masculino , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
15.
Diabetes Obes Metab ; 21(2): 439-443, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30226296

RESUMO

For patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic control, addition of basal insulin is recommended, but titration and optimization of basal insulin therapy in primary care is not well understood. We conducted an observational trial in 2470 patients with T2DM who initiated insulin glargine 100 U/L (Gla-100) on top of oral antidiabetic drugs. Physicians were free to choose either a "Davies," "Fritsche" or "individual" titration algorithm. We found that fasting blood glucose (FBG) and glycated haemoglobin (HbA1c) levels were effectively reduced by Gla-100; 65.9% of patients achieved the primary endpoint (FBG ≤6.1 mmol/L (110 mg/dL) or an individual HbA1c target). There were no significant differences in efficacy and safety between the algorithms used. The mean FBG decreased by 3.2 mmol/L (59 mg/dL) over 12 months, while the mean HbA1c decreased by 15.3 mmol/mol (1.4%)%. From a starting dose of 11.7 U/d, the Gla-100 dosage was 22.8 U/d at 12 months, with similar values in each group. Rates of hypoglycaemia were low and did not differ by titration algorithm. We conclude that Gla-100 was effective at reducing FBG and HbA1c, independent of the titration algorithm, but observed that algorithms were inconsistently applied in clinical practice.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cálculos da Dosagem de Medicamento , Hipoglicemiantes/administração & dosagem , Insulina Glargina/administração & dosagem , Administração Oral , Idoso , Algoritmos , Glicemia/efeitos dos fármacos , Calibragem , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Falha de Tratamento
16.
Diabet Med ; 36(1): 110-119, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30362181

RESUMO

AIM: To conduct an open-label study to provide UK real-world evidence regarding the use of insulin glargine 300 units/ml (U300) in people with Type 1 diabetes mellitus. METHODS: People with Type 1 diabetes who had been prescribed U300 ≥6 months before data collection and had HbA1c levels recorded within 3 months prior to U300 (baseline) were included. The primary endpoint was change in HbA1c from baseline to month 6 after U300 initiation. Other endpoints included number of documented hypoglycaemic and diabetic ketoacidosis episodes, and change in daily basal insulin dose. RESULTS: A total of 298 people with Type 1 diabetes were included [mean age 42.1 years, mean HbA1c 79 mmol/mol (9.4%)]. After U300 initiation, the mean reduction in HbA1c from baseline to month 6 was -4 mmol/mol (-0.4%; P<0.001; n=188). The total daily basal insulin dose at 6 months was 1.3 units higher than at the time of U300 initiation (P<0.001; n=275) but was not significantly different from the prior basal insulin dose. There was no clinically significant difference in weight between baseline and month 6 [mean difference +0.7 kg, 95% CI -0.1, 1.5; P=0.084; n=115). During the 6 months before and after U300 initiation, severe hypoglycaemic episodes were documented for 6/298 and 4/298 participants. Diabetic ketoacidosis episodes requiring Accident and Emergency department visits or hospitalization were documented for 4/298 and 6/298 participants, before and after U300 initiation, respectively. CONCLUSIONS: In people with Type 1 diabetes, a change in basal insulin to U300 was associated with clinically and statistically significant HbA1c improvements, without significant changes in basal insulin dose and weight. Documented severe hypoglycaemia episodes and diabetic ketoacidosis requiring Accident and Emergency department visits or hospitalization were low and similar before and after U300 initiation.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cetoacidose Diabética/prevenção & controle , Insulina Glargina/administração & dosagem , Insulina Glargina/uso terapêutico , Adulto , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/fisiopatologia , Cetoacidose Diabética/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Reino Unido/epidemiologia
17.
Diabetes Obes Metab ; 21(3): 622-630, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30362250

RESUMO

AIMS: To investigate the association between day-to-day fasting self-monitored blood glucose (SMBG) variability and risk of hypoglycaemia in type 1 (T1D) and type 2 diabetes (T2D), and to compare day-to-day fasting SMBG variability between treatments with insulin degludec (degludec) and insulin glargine 100 units/mL (glargine U100). MATERIALS AND METHODS: Data were retrieved from two double-blind, randomized, treat-to-target, two-period (32 weeks each) crossover trials of degludec vs glargine U100 in T1D (SWITCH 1, n = 501) and T2D (SWITCH 2, n = 720). Available fasting SMBGs were used to determine the standard deviation (SD) of day-to-day fasting SMBG variability for each patient and the treatment combination. The association between day-to-day fasting SMBG variability and overall symptomatic, nocturnal symptomatic and severe hypoglycaemia was analysed for the pooled population using linear regression, with fasting SMBG variability included as a three-level factor defined by population tertiles. Finally, day-to-day fasting SMBG variability was compared between treatments. RESULTS: Linear regression showed that day-to-day fasting SMBG variability was significantly associated with overall symptomatic, nocturnal symptomatic and severe hypoglycaemia risk in T1D and T2D (P < 0.05). Day-to-day fasting SMBG variability was significantly associated (P < 0.01) with all categories of hypoglycaemia risk, with the exception of severe hypoglycaemia in T2D when analysed within tertiles. Degludec was associated with 4% lower day-to-day fasting SMBG variability than glargine U100 in T1D (P = 0.0082) and with 10% lower day-to-day fasting SMBG variability in T2D (P < 0.0001). CONCLUSIONS: Higher day-to-day fasting SMBG variability is associated with an increased risk of overall symptomatic, nocturnal symptomatic and severe hypoglycaemia. Degludec has significantly lower day-to-day fasting SMBG variability vs glargine U100.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Jejum/sangue , Hipoglicemia/induzido quimicamente , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Adolescente , Adulto , Glicemia/metabolismo , Automonitorização da Glicemia , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Jejum/fisiologia , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Insulina Glargina/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
18.
Diabetes Obes Metab ; 21(3): 584-591, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30328252

RESUMO

AIMS: To investigate efficacy, safety and usability of the GlucoTab system for glycaemic management using insulin glargine U300 in non-critically ill hospitalized patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In this open, non-controlled single-arm pilot study, glycaemic control at the general ward of a tertiary care hospital was guided by a mobile decision support system (GlucoTab) for basal-bolus insulin dosing using the novel basal insulin analogue insulin glargine U300 for the first time. Glycaemic control was surveilled with capillary glucose measurements and continuous glucose monitoring (CGM). The primary endpoint was efficacy of glycaemic management, defined as the percentage of blood glucose measurements within the target range of 3.9 to 7.8 mmol/L. RESULTS: A total of 30 patients with T2D (12 female; age, 67 ± 11 years; HbA1c, 70 ± 26 mmol/mol; BMI, 31.8 ± 5.6 kg/m2 ; length of study, 8.5 ± 4.5 days) were included. In total, 894 capillary glucose values and 49 846 data points of CGM were available, of which 56.1% of all measured capillary glucose values and 54.3% of CGM values were within the target area (3.9-7.8 mmol/L). Overall capillary mean glucose was 8.5 ± 1.2 and 8.4 ± 1.2 mmol/L assessed by CGM. Time within glucose target improved continuously during the course of treatment, while time within hypoglycaemia (<3.9 mmol/L) decreased substantially. The GlucoTab-suggested total daily dose was accepted by staff in 97.3% of situations. CONCLUSIONS: Treatment with GlucoTab using insulin glargine U300 in hospitalized patients with T2D is effective and safe.


Assuntos
Glicemia/análise , Técnicas de Apoio para a Decisão , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina Glargina/administração & dosagem , Aplicativos Móveis , Idoso , Algoritmos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Automonitorização da Glicemia/instrumentação , Automonitorização da Glicemia/métodos , Cálculos da Dosagem de Medicamento , Feminino , Hospitalização , Humanos , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Risco
19.
J Pharm Pract ; 32(4): 447-449, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30270723

RESUMO

The US Food and Drug Administration recently approved 2 combination products containing a basal insulin and a glucagon-like peptide 1 receptor agonist: insulin glargine/lixisenatide and insulin degludec/liraglutide. These agents were shown to be noninferior in lowering hemoglobin A1c compared to basal insulin and are indicated for patients inadequately controlled on basal insulin or glucagon-like peptide 1 receptor agonists alone. The clinical implications of these agents are unclear due to limitations in the clinical trials and limited recommendations in current guidelines. While these agents may provide financial and adherence benefits, their role is likely limited to the outpatient setting. With the availability of these agents, concerns with transitions of care arise due to multiple vulnerabilities in reconciling these agents throughout the inpatient admission and discharge process. Provider awareness of the availability and dosing of insulin glargine/lixisenatide and insulin degludec/liraglutide is essential to reduce errors in the medication reconciliation process.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/administração & dosagem , Aprovação de Drogas , Combinação de Medicamentos , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Hipoglicemiantes/farmacologia , Insulina Glargina/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Liraglutida/administração & dosagem , Adesão à Medicação , Peptídeos/administração & dosagem , Guias de Prática Clínica como Assunto
20.
Diabetes Care ; 42(1): 85-92, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30305345

RESUMO

OBJECTIVE: This study characterized the pharmacokinetics (PK), pharmacodynamics (PD), and endogenous (hepatic) glucose production (EGP) of clinical doses of glargine U300 (Gla-300) and glargine U100 (Gla-100) under steady-state (SS) conditions in type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS: T1DM subjects (N = 18, age 40 ± 12 years, T1DM duration 26 ± 12 years, BMI 23.4 ± 2 kg/m2, A1C 7.19 ± 0.52% [55 ± 5.7 mmol · mol-1-1]) were studied after 3 months of Gla-300 or Gla-100 (evening dosing) titrated to fasting euglycemia (random, crossover) with the euglycemic clamp using individualized doses (Gla-300 0.35 ± 0.08, Gla-100 0.28 ± 0.07 units · kg-1). RESULTS: Plasma free insulin concentrations (free immunoreactive insulin area under the curve) were equivalent over 24 h with Gla-300 versus Gla-100 (point estimate 1.11 [90% CI 1.03; 1.20]) but were reduced in the first 6 h (0.91 [90% CI 0.86; 0.97]) and higher in the last 12 h postdosing (1.38 [90% CI 1.21; 1.56]). Gla-300 and Gla-100 both maintained 24 h euglycemia (0.99 [90% CI 0.98; 1.0]). The glucose infusion rate was equivalent over 24 h (1.03 [90% CI 0.88; 1.21]) but was lower in first (0.77 [90% CI 0.62; 0.95]) and higher (1.53 [90% CI 1.23; 1.92]) in the second 12 h with Gla-300 versus Gla-100. EGP was less suppressed during 0-6 h but more during 18-24 h with Gla-300. PK and PD within-day variability (fluctuation) was 50% and 17% lower with Gla-300. CONCLUSIONS: Individualized, clinical doses of Gla-300 and Gla-100 resulted in a similar euglycemic potential under SS conditions. However, Gla-300 exhibited a more stable profile, with lower variability and more physiological modulation of EGP compared with Gla-100.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina Glargina/administração & dosagem , Insulina Glargina/farmacocinética , Adulto , Índice de Massa Corporal , Estudos Cross-Over , Relação Dose-Resposta a Droga , Jejum , Feminino , Técnica Clamp de Glucose , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Insulina/sangue , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Método Simples-Cego
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