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1.
Cardiol Rev ; 27(5): 260-266, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31393288

RESUMO

Long-acting basal insulins are used for the management of both type 1 and type 2 diabetes mellitus. Long-acting basal insulins were developed utilizing recombinant DNA technology and have been available since 2000 with the approval of insulin glargine U-100 followed by insulin detemir in 2005. In recent years, diabetes management has become more complex with the approval of insulin glargine U-300 and insulin degludec U-100 and U-200. Both insulin glargine U-300 and insulin degludec have been compared with insulin glargine U-100 and have demonstrated longer durations of action, as well as lower rates of hypoglycemia. This review discusses the Food and Drug Administration-approved long-acting insulins with a focus on recently approved agents and their efficacy and safety compared with the first long-acting basal insulins.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Guias de Prática Clínica como Assunto , Ensaios Clínicos como Assunto , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Masculino
2.
BMC Endocr Disord ; 19(1): 78, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337371

RESUMO

BACKGROUND: Hypoglycaemia, especially nocturnal, remains the main limiting factor of achieving good glycaemic control in type 1 diabetes. The effect of first generation long-acting insulin analogues in reducing nocturnal hypoglycaemia is well documented in patient with type 1 diabetes. The effect of the newer long-acting insulin degludec on risk of nocturnal hypoglycaemia remains undocumented in patients with type 1 diabetes and recurrent severe nocturnal hypoglycaemia. The HypoDeg trial is designed to investigate whether insulin degludec in comparison with insulin glargine U100 is superior in limiting the occurrence of nocturnal hypoglycaemia in patients with recurrent nocturnal severe hypoglycaemia. This paper reports the study design of the HypoDeg trial. METHODS/DESIGN: A Danish investigator-initiated, prospective, randomised, open, blinded endpoint (PROBE), multicentre, two-year cross-over study investigating the effect of insulin degludec versus insulin glargine U100 on frequency of nocturnal hypoglycaemia in patients with type 1 diabetes and one or more episodes of nocturnal severe hypoglycaemia during the preceding two years as the major inclusion criteria. Patients are randomised (1:1) to basal therapy with insulin degludec or insulin glargine. Insulin aspart is used as bolus therapy in both treatment arms. DISCUSSION: In contrast to most other insulin studies the HypoDeg trial includes only patients at high risk of hypoglycaemia. The HypoDeg trial will compare treatment with insulin degludec to insulin glargine U100 in terms of risk of nocturnal hypoglycaemic episodes in patients with type 1 diabetes with the greatest potential to benefit from near-physiological insulin replacement therapy. www.clinicaltrials.gov : NCT02192450.


Assuntos
Ritmo Circadiano/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/epidemiologia , Hipoglicemiantes/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Biomarcadores/análise , Glicemia/análise , Estudos Cross-Over , Esquema de Medicação , Feminino , Seguimentos , Humanos , Hipoglicemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Adulto Jovem
3.
Rev Med Liege ; 74(4): 226-232, 2019 Apr.
Artigo em Francês | MEDLINE | ID: mdl-30997973

RESUMO

Insulin degludec (Tresiba®) is characterized by an original mode of prolonged and continuous insulin release after its subcutaneous injection. Thereby, it has a very long glucose-lowering effect, around 42 hours, and a better reproducibility from both a pharmacokinetic and pharmacodynamic point of view. Its efficacy and safety have been assessed in the phase 3 clinical programme BEGIN as compared with insulin glargine U100, in patients with type 1 diabetes (T1D) and type 2 (T2D). For a similar glucose control (reduction in glycated haemoglobin), less hypoglycaemic episodes were recorded, including severe hypoglycaemia, during the nocturnal period, with insulin degludec than with insulin glargine U100. This clinical benefit has been confirmed in the complementary SWITCH programme in T1D and T2D patients at higher risk of hypoglycaemia, in the double-blind cardiovascular outcome trial DEVOTE in T2D patients at high cardiovascular risk and in real-life conditions in the observational European EU-TREAT study in patients with T1D and T2D. Insulin degludec (Tresiba®) is indicated and reimbursed for the treatment of patients with T1D, combined with a prandial insulin, and T2D, alone or combined with oral antidiabetic agents, a glucagon-like peptide-1 receptor agonist or a short-acting insulin.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Hipoglicemiantes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Hemoglobina A Glicada , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina Glargina , Insulina de Ação Prolongada/farmacologia , Insulina de Ação Prolongada/uso terapêutico , Estudos Observacionais como Assunto , Reprodutibilidade dos Testes
4.
Can J Diabetes ; 43(7): 515-523, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30872107

RESUMO

Limiting postprandial glucose (PPG) excursions is an important aspect of overall glycemic control. Rapid-acting insulin analogues (RAIAs) aim to mimic the physiologic action of endogenous insulin observed in individuals without diabetes and prevent excessive PPG excursions. However, many people with type 1 diabetes and type 2 diabetes treated with RAIAs do not achieve glycated hemoglobin (A1C) targets, and there is an unmet need for further improvements in PPG control. Current RAIAs have a delayed onset and a longer duration of action compared with endogenous insulin secreted in response to meals. Approaches to developing new mealtime insulins with accelerated absorption kinetics include changing the route of administration (i.e. via inhalation) and changing the insulin formulation. Fast-acting insulin aspart (faster aspart) is a novel formulation of insulin aspart (IAsp) containing the excipients niacinamide and L-arginine. Faster aspart has an earlier onset of insulin exposure and a greater early glucose-lowering effect than IAsp. In large clinical trials, mealtime faster aspart demonstrated noninferiority to IAsp with respect to A1C reduction and provided superior PPG control with no increase in overall severe or blood glucose-confirmed hyperglycemia. In addition, faster aspart administered up to 20 min after the start of a meal was noninferior to mealtime IAsp in terms of A1C control, highlighting the opportunity for postmeal dosing. Faster aspart is the first of a new generation of mealtime insulins to be approved in Canada for the treatment of adults with type 1 diabetes and type 2 diabetes, and it is included in the 2018 Diabetes Canada clinical practice guidelines.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Aspart/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Período Pós-Prandial , Adulto , Glicemia/análise , Canadá , Diabetes Mellitus Tipo 2/sangue , Combinação de Medicamentos , Hemoglobina A Glicada/análise , Humanos , Prognóstico
6.
Endocr Pract ; 25(3): 226-229, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30913005

RESUMO

OBJECTIVE: Many youth with diabetes struggle to meet glycemic targets. The new ultralong duration of action of insulin degludec (iDeg) holds potential to ameliorate missed doses of basal insulin and improve glycemic control in youth with diabetes. METHODS: A retrospective chart review was undertaken of youth age 13 to <24 years in our practice with type 1 diabetes (T1D) or type 2 diabetes (T2D) who had been switched from glargine or detemir to iDeg to evaluate the impact of this transition on glycemic control. RESULTS: Glycated hemoglobin A1c (HbA1c) in youth with T1D (n = 82) remained stable during 6 months of treatment with iDeg (10.1 ± 2.11% [87 ± 23 mmol/mol] at start of iDeg compared to 10.1 ± 2.12% [87 ± 23 mmol/mol] at 6 months of treatment), whereas in youth with T2D (n = 16), HbA1c significantly declined from 10.6 ± 2.3% (92 ± 25 mmol/mol) to 8.3 ± 2.2% (67 ± 24 mmol/mol) ( P = .0024). CONCLUSION: In youth switched to iDeg, which in our practice is commonly due to ineffectiveness of the patient's current regimen, the outcome differences we saw may be due to preserved beta-cell function in youth with T2D. It remains to be seen whether there are benefits of transition to iDeg in youth with T1D beyond glycemic outcomes, such as reduction in ketosis and episodes of diabetic ketoacidosis. ABBREVIATIONS: DKA = diabetic ketoacidosis; DPV = Diabetes-Patienten-Verlaufsdokumentation (German/Austrian Prospective Diabetes Follow-Up Registry); HbA1c = glycated hemoglobin A1c; iDeg = insulin degludec; T1D = type 1 diabetes; T2D = type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Insulina de Ação Prolongada/uso terapêutico , Hemoglobina A Glicada , Humanos , Hipoglicemiantes , Insulina Glargina , Estudos Prospectivos , Estudos Retrospectivos
7.
Life Sci ; 219: 90-99, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30639280

RESUMO

Insulin remains a predominant life-saving medication for type 1 and type 2 Diabetes Mellites. Natural insulin secretion limits the fluctuation of the narrow and high surge of blood glucose levels. However, imitating the same by external insulin remains a challenge as a variety of insulin analogs (rapid acting, short acting, intermediate acting and long-acting) have different pharmacokinetic (PK) and pharmacodynamic (PD) properties. Inconsistent reduction in overall hyperglycemia level and nocturnal hypoglycemia due to variable absorption time and time action profile predominantly highlights the need of revisiting the PK/PD of insulin analogs as single analog is not yet sufficed to replace internal insulin exogenously. Combination therapy with basal and prandial insulins or intensification of hypoglycemic therapy with premixed insulins are of prime importance in managing diabetes effectively, imitating the natural insulin secretion. Therefore, the knowledge of PK/PD properties might help a practitioner to design, implement and manage insulin replacement therapy effectively and averting adverse events. Present study reports the comparative analysis of PK/PD profile of various insulin analogs based on the concurrent information about clinical aspects. Moreover, study interlinks the major concerns of therapeutic efficacy of insulin analogs with their respective onset of action and duration of effectiveness and reported adverse drug reaction which explore the scope of improvement.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Insulina/análogos & derivados , Previsões , Humanos , Insulina/uso terapêutico , Insulina Aspart/uso terapêutico , Insulina Detemir/uso terapêutico , Insulina Glargina/uso terapêutico , Insulina Lispro/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico
8.
Postgrad Med ; 131(2): 117-128, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30691343

RESUMO

The treatment of type 2 diabetes (T2D) is often complicated by factors such as patient co-morbidities, complex drug-drug interactions, and management of adverse events. In addition, some of these factors are highly dependent on the nature of the treatment regimen and the molecular and physical properties of the drugs being used to treat patients with this disease. This calls for a better understanding of how the properties of individual drugs affect the overall outcome for patients with diabetes. Clinical pharmacology studies to assess the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of new diabetes drugs play an important role in advancing our understanding of the interactions between a drug and the human body. Specific PK and PD techniques such as the glucose clamp test can be applied to assess the properties of drugs used for the treatment of diabetes. Basal insulin analogs are a common treatment option for the maintenance of glycemic control in patients with T2D. These drugs work by mimicking endogenous insulin secretion within the body and provide stable and prolonged insulin action to achieve optimal glucose levels. Insulin glargine 300 U/mL (Gla-300) and insulin degludec (IDeg) 100 U/mL and 200 U/mL represent a new generation of longer-acting basal insulins. These drugs demonstrate improved PK and PD properties compared with previous basal insulins, allowing them to more closely mimic physiological basal insulin secretion. Here we review the methods used to evaluate the PK and PD profiles of Gla-300 and IDeg and describe studies that have investigated the PK/PD properties of these drugs in type 1 diabetes. The aim of this review is to inform primary care physicians of the value and limitations of data from clinical pharmacology studies when prescribing these agents for the management of T2D.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina de Ação Prolongada/farmacocinética , Humanos , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina de Ação Prolongada/farmacologia , Insulina de Ação Prolongada/uso terapêutico
9.
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
10.
Adv Ther ; 36(2): 265-277, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30610613

RESUMO

The progressive nature of type 2 diabetes (T2D) means that many patients will require basal insulin therapy at some point in the course of the disease due to ß-cell failure. As basal insulin primarily targets fasting plasma glucose, patients may still experience considerable postprandial glucose excursions and therefore require an additional agent to achieve good glycemic control. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide an alternative to prandial insulin, with the benefits of fewer daily injections, and a lower risk of hypoglycemia and weight gain. Two fixed-ratio combinations (FRCs) of basal insulin and a GLP-1 RA are now available in the USA and the EU: insulin glargine + lixisenatide (iGlarLixi) and insulin degludec + liraglutide (IDegLira). Titratable FRCs are suitable for most patients with T2D and can help to simplify treatment regimens into one daily injection, potentially aiding in patient adherence. The complementary modes of action of the two components target seven of the many known pathophysiologic defects in T2D. FRCs have demonstrated enhanced glycemic control compared with their constituent components alone, comparable risk of hypoglycemia compared with basal insulin alone, and better tolerability compared with the GLP-1RA component alone due to the slower titration. In this article, we discuss the advantages of FRCs over multiple daily injections, present case studies of typical patients who could benefit from FRC therapy, and outline practical considerations for the initiation of FRC therapy in clinical practice.Funding Sanofi.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Insulina/uso terapêutico , Terapia Combinada , Combinação de Medicamentos , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Hemoglobina A Glicada/análise , Humanos , Liraglutida/administração & dosagem , Cooperação do Paciente , Período Pós-Prandial , Ganho de Peso
11.
Ther Innov Regul Sci ; 53(2): 279-286, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29793353

RESUMO

BACKGROUND: In 2013, a randomized, double-blind, active comparator-controlled, event-driven cardiovascular outcomes trial (DEVOTE) was initiated to compare the cardiovascular safety of insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes at high risk of cardiovascular events. The FDA agreed that an interim analysis could form the basis for an early regulatory approval. We report here the operational model developed to support the DEVOTE interim analysis and the results. METHODS: The interim analysis model was designed to reduce the risk of any confidentiality breaches. The Data Access Management Plan comprehensively described the interim analysis operational processes and procedures to maintain the integrity of the ongoing trial while the interim analysis was conducted, submitted, and acted upon by the FDA, and also until completion of the full trial. Most importantly, those who were unblinded to the interim results were limited to a team of 14 members. RESULTS: A total of 150 first major adverse cardiovascular events were recorded at cut-off for the interim analysis. The estimated hazard ratio was 0.92 (95% CI 0.67, 1.27) and non-inferiority to glargine U100 was confirmed as the upper bound of the confidence interval was below 1.8, as prespecified. Based on these results, the FDA approved the use of degludec and degludec/insulin aspart (IDegAsp) in the United States in 2015 before trial completion. CONCLUSIONS: The DEVOTE interim analysis succeeded as a model by which to conduct an interim analysis and submit confidential data for regulatory review and action while continuing the trial to address a primary hypothesis.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Sistema Cardiovascular/efeitos dos fármacos , Método Duplo-Cego , Humanos , Resultado do Tratamento
12.
J Diabetes Investig ; 10(2): 343-351, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29947060

RESUMO

AIMS/INTRODUCTION: Compared with glargine 100 U/mL (Gla100), glargine 300 U/mL (Gla300) and degludec (Deg) - the ultralong-acting insulins - reportedly have more stable effects and reduce the risk of hypoglycemia. Currently, they are considered to be the most useful basal insulins. The present study aimed to compare the efficacy and safety of Gla300 and Deg on glycemic control using continuous glucose monitoring. MATERIALS AND METHODS: In this single-center, open-label, parallel-group, two-period, cross-over study, 30 patients with type 2 diabetes were randomized to once-daily Gla300 followed by Deg with the same units (n = 15) or vice versa (n = 15). The primary end-points of this study were the mean percentage of time within the target glucose range of 70-180 mg/dL as efficacy and hypoglycemia of <70 mg/dL as safety indicators, as measured using continuous glucose monitoring during each treatment period. RESULTS: The mean percentage of time within the target glucose range was not different between Gla300 and Deg (77.8 ± 19.2 vs 76.9 ± 18.3%, P = 0.848). However, the mean percentage of time of hypoglycemia with Gla300 was significantly lower than that of Deg (1.3 ± 2.7 vs 5.5 ± 6.4%, P = 0.002). In the secondary safety end-points, the mean percentage of time of severe hypoglycemia (<54 mg/dL) or nocturnal hypoglycemia with Gla300 was also significantly lower than that of Deg. CONCLUSIONS: The present study showed the comparable efficacy of Gla300 and Deg on glycemic control; however, the risk of hypoglycemia was markedly lower for Gla300 than for Deg.


Assuntos
Biomarcadores/análise , Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Idoso , Automonitorização da Glicemia/métodos , Estudos Cross-Over , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Masculino , Prognóstico , Segurança
13.
Endocr Pract ; 25(2): 144-155, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30383495

RESUMO

OBJECTIVE: The efficacy and safety of insulin degludec/liraglutide (IDegLira) in older patients has not yet been reported. This analysis aimed to evaluate the efficacy and safety of IDegLira in patients aged ≥65 years. METHODS: A post hoc analysis compared results of patients aged ≥65 versus <65 years from DUAL II, III, and V. These were 26-week, phase 3, randomized, twoarm parallel, treat-to-target trials in patients already taking injectable glucose-lowering agents. We evaluated 311 patients aged <65 and 87 patients aged ≥65 years from DUAL II, 326 patients <65 years and 112 patients ≥65 years from DUAL III, and 412 patients <65 years and 145 patients ≥65 years from DUAL V. Patients were randomized to IDegLira or insulin degludec (DUAL II), IDegLira or unchanged glucagon-like peptide 1-receptor agonist (GLP-1RA) (DUAL III), or IDegLira or IGlar U100 (DUAL V). RESULTS: In patients ≥65 years, hemoglobin A1C decreased to a greater extent with IDegLira than with comparators (estimated treatment differences, -1.0% [-1.5; -0.6]95% confidence interval [CI], -0.8% [-1.0; -0.5]95% CI, and -0.9% [-1.3; -0.6]95%CI) for DUAL II, V, and III, respectively; all P<.001). These mirrored results of patients <65 years of age. Hypoglycemia rates were lower with IDegLira versus basal insulin and higher versus unchanged GLP-1RA (estimated rate ratios, 0.5 [0.2; 1.6]95% CI [ P = .242]; 0.3 [0.1; 0.5]95% CI [ P<.001], and 11.8 [3.3; 42.8]95% CI [ P<.001] for DUAL II, V, and III, respectively). CONCLUSION: Patients aged ≥65 years on basal insulin or GLP-1RA can improve glycemic control with IDegLira, and it is well tolerated overall. ABBREVIATIONS: A1C = hemoglobin A1C; AE = adverse event; CI = confidence interval; Degludec = insulin degludec; EOT = end of trial; ETD = estimated treatment difference; FPG = fasting plasma glucose; GLP-1RA = glucagon-like peptide 1 receptor agonist; IDegLira = insulin degludec/liraglutide; IGlar U100 = insulin glargine 100 U/mL; SU = sulfonylurea; T2D = type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Idoso , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Combinação de Medicamentos , Hemoglobina A Glicada , Humanos , Hipoglicemiantes , Insulina Glargina , Insulina de Ação Prolongada/uso terapêutico , Liraglutida/uso terapêutico
14.
J Diabetes Investig ; 10(2): 352-357, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29989335

RESUMO

AIMS/INTRODUCTION: We compared the efficacy and safety of insulin glargine 300 U/mL (Gla300) and insulin degludec U100 (Deg) using a flash glucose monitoring system. MATERIALS AND METHODS: A total of 24 Japanese patients with type 2 diabetes were randomized to receive once-daily Gla300 (n = 12) or Deg (n = 12) in the morning. The primary end-points were the mean percentage of time in the target glucose range (70-179 mg/dL) and hypoglycemia (<70 mg/dL), as measured using flash glucose monitoring during the last 7 days of each 14-day period. RESULTS: The percentages of time with glucose levels <70 mg/dL were not significantly different between the two insulin treatments. No significant differences were observed in the percentages of time with glucose levels of 70-179 mg/dL or ≥180 mg/dL. The percentage of time with nocturnal hypoglycemia with Gla300 was significantly lower than that with Deg treatment (P = 0.021). This difference might be attributable to the difference in the duration of action between the two formulations, and the incidence of nocturnal hypoglycemia with Deg treatment was associated with the concomitant use of metformin (P = 0.035). CONCLUSIONS: The two formulations were comparable in efficacy, whereas the incidence of nocturnal hypoglycemia was significantly lower with Gla300. Thus, the present study suggests that, although Gla300 and Deg are comparable long-acting insulin analogs, Gla300 is safer with respect to the incidence of hypoglycemia.


Assuntos
Biomarcadores/análise , Automonitorização da Glicemia/métodos , Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Idoso , Estudos Cross-Over , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Masculino , Prognóstico
15.
Rev. chil. endocrinol. diabetes ; 12(1): 6-10, 2019. graf, tab
Artigo em Espanhol | LILACS | ID: biblio-981150

RESUMO

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.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Insulina de Ação Prolongada/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Hemoglobina A Glicada/análise , Seguimentos , Diabetes Mellitus Tipo 1/sangue , Insulina Glargina/efeitos adversos , Insulina Glargina/uso terapêutico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos
16.
Endocr Pract ; 24(9): 796-804, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30308134

RESUMO

OBJECTIVE: In the DUAL (Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes) VII trial, IDegLira (a combination of insulin degludec and liraglutide) was compared with insulin glargine U100 plus insulin aspart. Both treatment approaches achieved similar glycemic control, but there were differences in hypoglycemia, changes in body weight, and injection frequency. The aim of the present analysis was to assess the short-term cost effectiveness of IDegLira versus insulin glargine U100 plus insulin aspart for treatment of patients with type 2 diabetes mellitus not meeting glycemic targets on basal insulin in the U.S. METHODS: A cost-utility model was developed to evaluate the clinical and economic outcomes associated with the 2 treatments over a 1-year time horizon, capturing the impact on quality of life of hypoglycemic events, body mass index, and injection frequency. Costs were captured from a healthcare payer perspective in 2017 U.S. dollars ($). RESULTS: IDegLira was associated with improved quality of life by 0.12 quality-adjusted life years compared with insulin glargine U100 plus insulin aspart. The key drivers of this difference were reduced injection frequency and hypoglycemic events avoided. IDegLira was associated with increased annual drug costs, but this was entirely offset by reduced needle costs and reduced costs of self-monitoring of blood glucose testing. IDegLira was associated with total annual cost savings of $743 per patient. CONCLUSION: IDegLira was found to improve quality-adjusted life expectancy and reduce costs when compared with insulin glargine U100 plus insulin aspart for treatment of patients with type 2 diabetes not achieving glycemic control on basal insulin in the U.S. ABBREVIATIONS: ADA = American Diabetes Association; BMI = body mass index; CI = confidence interval; DUAL = Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes; GLP-1 = glucagon-like peptide-1; HbA1c = glycated hemoglobin; ICER = incremental cost-effectiveness ratio; IU = international units; QALY = quality-adjusted life year; SMBG = self-monitoring of blood glucose.


Assuntos
Redução de Custos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Aspart/uso terapêutico , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Liraglutida/uso terapêutico , Combinação de Medicamentos , Humanos , Hipoglicemiantes/economia , Insulina Glargina/economia , Insulina de Ação Prolongada/economia , Expectativa de Vida , Liraglutida/economia
17.
J Vet Med Sci ; 80(11): 1720-1723, 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30305465

RESUMO

Insulin degludec (IDeg) is a new insulin formulation that facilitates long-term control of glucose level in humans. In this study, we investigated the effects of IDeg on glycemic control in dogs. Its time-action profiles were monitored in healthy dogs using an artificial pancreas apparatus under euglycemic conditions. At 9.0-13.5 hr post-IDeg injection, an indistinct peak of glucose level was detected. Moreover, the action of IDeg was persistent for >20 hr. Both IDeg and neutral protamine Hagedorn insulin (NPH) lowered blood glucose concentrations in diabetic dogs, but IDeg caused postprandial hyperglycemia and a somewhat lower preprandial glucose level than that caused by NPH. IDeg might be ineffective in concurrently preventing postprandial hyperglycemia and preprandial hypoglycemia in a single-agent administration.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/veterinária , Doenças do Cão/tratamento farmacológico , Insulina de Ação Prolongada/uso terapêutico , Animais , Glicemia , Cães , Relação Dose-Resposta a Droga , Insulina Isófana/administração & dosagem , Insulina Isófana/uso terapêutico , Insulina de Ação Prolongada/administração & dosagem
18.
Rev Med Liege ; 73(10): 526-532, 2018 Oct.
Artigo em Francês | MEDLINE | ID: mdl-30335259

RESUMO

Xultophy® (IDegLira) is a fixed ratio combination of basal insulin degludec and glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide. Insulin degludec is characterized by an original mode of prolonged and continuous insulin diffusion after its subcutaneous injection. Thereby, it has a very long half-life, around 25 hours, and a better reproducibility from both a pharmacokinetic and pharmacodynamic point of view, with less hypoglycaemia, especially at night. Liraglutide is a well-known once-daily GLP-1 receptor agonist that showed a cardiovascular and renal protection in patients with type 2 diabetes at high cardiovascular risk. Both molecules exert complementary antihyperglycaemic effects, which allows a better glucose control, both in the fasting and postprandial states. IDegLira is more effective than another basal insulin regimen in reaching individualized glycated haemoglobin target, with a lower daily dose of insulin. It has a better tolerance profile, with a more favourable effect on body weight and less hypoglycaemia compared with a basal insulin and less gastrointestinal adverse effects when compared with liraglutide alone. Xultophy® is presented as a prefilled pen and is indicated in the management of type 2 diabetes not well controlled with basal insulin. The dose of IDegLira is progressively uptitrated, starting from 16 dose steps up to a maximum of 50 dose steps per day (corresponding to 50 IU insulin degludec and 1.8 mg liraglutide).


Assuntos
Hipoglicemiantes/farmacologia , Insulina de Ação Prolongada/farmacologia , Liraglutida/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Combinação de Medicamentos , Humanos , Hipoglicemiantes/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico
19.
Diabetes Obes Metab ; 20(12): 2885-2893, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30259644

RESUMO

AIM: To evaluate the efficacy and safety of mealtime or post-meal fast-acting insulin aspart (faster aspart) vs mealtime insulin aspart (IAsp), both in combination with insulin degludec, in participants with type 1 diabetes (T1D). METHODS: This multicentre, treat-to-target trial (Clinical trial registry: NCT02500706, ClinicalTrials.gov) randomized participants to double-blind mealtime faster aspart (n = 342) or IAsp (n = 342) or open-label post-meal faster aspart (n = 341). The primary endpoint was change from baseline in HbA1c 26 weeks post randomization. All available information, regardless of treatment discontinuation, was used for evaluation of the effect. RESULTS: Non-inferiority for the change from baseline in HbA1c was confirmed for mealtime and post-meal faster aspart vs IAsp (estimated treatment difference [ETD]: 95%CI, -0.02% [-0.11; 0.07] and 0.10% [0.004; 0.19], respectively). Mealtime faster aspart was superior to IAsp for 1-hour PPG increment using a meal test (ETD, -0.90 mmol/L [-1.36; -0.45]; P < 0.001). Self-monitored 1-hour PPG increment favoured faster aspart at breakfast (ETD, -0.58 mmol/L [-0.99; -0.17]; P = 0.006) and across all meals (-0.48 mmol/L [-0.74; -0.21]; P < 0.001). Safety profiles and overall rate of severe or blood glucose-confirmed hypoglycaemia were similar between treatments, but significantly less hypoglycaemia was seen 3 to 4 hours after meals with mealtime faster aspart. CONCLUSION: Mealtime and post-meal faster aspart in conjunction with insulin degludec provided effective glycaemic control compared with IAsp, with no increased safety risk. Mealtime faster aspart provided PPG control superior to that of IAsp.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Aspart/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Adolescente , Adulto , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/sangue , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Hipoglicemia/induzido quimicamente , Masculino , Refeições/efeitos dos fármacos , Pessoa de Meia-Idade , Período Pós-Prandial/efeitos dos fármacos , Resultado do Tratamento , Adulto Jovem
20.
J Med Econ ; 21(11): 1110-1118, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30114954

RESUMO

AIMS: The clinical and economic impact of diabetes is growing in the US. Choosing therapies that are both effective and cost-effective is becoming increasingly important. The aim of the present analysis was to assess the long-term cost-effectiveness of IDegLira for treatment of patients with type 2 diabetes mellitus not meeting glycemic targets on basal insulin, vs insulin glargine U100 plus insulin aspart, in the US setting. MATERIALS AND METHODS: Long-term projections of cost-effectiveness outcomes were made using the IQVIA CORE Diabetes Model. Clinical inputs were based on the DUAL VII trial, with costs (accounted from a healthcare payer perspective) and utilities based on published sources. Future costs and clinical benefits were discounted at 3% annually. RESULTS: IDegLira was associated with increased discounted life expectancy by 0.02 years and increased discounted quality-adjusted life expectancy by 0.22 quality-adjusted life years compared with insulin glargine U100 plus insulin aspart. Evaluation of direct medical costs suggested that the mean cost per patient with IDegLira was $3,571 lower than with insulin glargine U100 plus insulin aspart. The cost saving was driven predominantly by the lower acquisition cost of IDegLira compared with insulin glargine U100 plus insulin aspart, with further cost savings identified as a result of avoided treatment of diabetes-related complications. IDegLira was associated with improved clinical outcomes at a reduced cost compared with insulin glargine U100 plus insulin aspart. CONCLUSIONS: Based on clinical trial data, the present analysis suggests that IDegLira is associated with improved clinical outcomes and cost savings compared with treatment with insulin glargine U100 plus insulin aspart for patients with type 2 diabetes not achieving glycemic control on basal insulin in the US. Therefore, IDegLira is likely to be considered dominant (cost saving and more effective) and, consequently, highly cost-effective in the US setting.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/economia , Insulina Aspart/economia , Insulina Glargina/economia , Insulina de Ação Prolongada/economia , Liraglutida/economia , Idoso , Análise Custo-Benefício , Complicações do Diabetes/economia , Complicações do Diabetes/epidemiologia , Combinação de Medicamentos , Feminino , Hemoglobina A Glicada/análise , Gastos em Saúde , Humanos , Hipoglicemiantes/uso terapêutico , Insulina Aspart/uso terapêutico , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Lipídeos/sangue , Liraglutida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Modelos Econométricos , Método de Monte Carlo , Anos de Vida Ajustados por Qualidade de Vida
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