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1.
BMJ Open Diabetes Res Care ; 7(1): e000679, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31641521

RESUMO

We summarize here clinical and trial data on a once-daily administration of a single bolus to the meal with the largest expected postprandial glucose excursion (basal-plus), and comment on its clinical utility in the treatment of type 2 diabetes. A PubMed search of data published until September 2018 was taken into consideration and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Eighteen reports representing 15 studies were identified (age: 18-80 years; 50-890 patients; follow-up: 8 days to 60 weeks). Data suggest basal-plus is efficacious for improving glycemic control, with a low incidence of (severe) hypoglycemia and minor increases in bodyweight. The timing of short-acting insulin administration and use of different monitoring/titration approaches appear to have minimal impact. When compared with premixed insulin, basal-plus results in largely comparable outcomes. Compared with basal-bolus, it may result in non-inferior glycemic improvements with less weight gain, less hypoglycemia and fewer daily injections. A basal insulin/glucagon-like peptide-1 receptor agonist fixed ratio combination may offer several advantages over the basal-plus regimen, at the cost of gastrointestinal side effects. We conclude that the stepwise introduction of short-acting insulin via the basal-plus strategy represents a viable alternative to a full basal-bolus regimen and may help to overcome barriers associated with multiple injections and anticipated complexity of the insulin regimen.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Curta/administração & dosagem , Administração Oral , Humanos
2.
J Manag Care Spec Pharm ; 25(11): 1162-1171, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31405345

RESUMO

BACKGROUND: As new biosimilar and follow-on insulins enter the market, more data are needed on safety, effectiveness, and patterns of use for these products to inform prescriber and patient decision-making regarding treatment. Additionally, data are needed regarding real-world patterns of use to inform future studies comparing the safety and effectiveness of bio-similars to already approved agents for diabetes treatment. OBJECTIVE: To analyze the medication use patterns, adverse events, and availability of glycated hemoglobin (A1c) values for adult patients with type 2 diabetes mellitus (T2DM) who use long-acting insulin (LAI) or neutral protamine Hagedorn (NPH), an intermediate-acting insulin. METHODS: We used the Biologics and Biosimilars Collective Intelligence Consortium's (BBCIC) distributed research network (DRN) for this descriptive analysis. The analysis time frame was January 1, 2011, to September 30, 2015, and included patients continuously insured for at least 183 days before the first date of a filled prescription for LAI or NPH insulin alone or with rapid- or short-acting insulin or sulfonylureas, whether newly starting insulin or switching to a different product. Insulin exposure episodes were the unit of analysis, and patients were classified in cohorts according to treatment. We followed patients until end of health plan enrollment or the end of the study period. We used occurrence of a study outcome, switch to another medication regimen, discontinuation of the current medication, or study end date to mark the end of an insulin episode. We describe demographics and availability of A1c values for analysis. Study outcomes included severe hypoglycemic events and major adverse cardiac events (MACE). RESULTS: We identified 103,951 patients with T2DM from a database of 39.1 million patients with commercial or Medicare Advantage pharmacy and medical benefits, who contributed 279,533 unique insulin exposure episodes. Most episodes (89%) included patients using LAI, and 52% of patients contributed data to 2 or more exposure cohorts. Insulin episodes lasted an average of 3.5 months, and patients had an average follow-up of 8.6 months. The unadjusted rate of severe hypoglycemic events requiring medical attention was 96.9 per 10,000 patient-years at risk (10kPYR). The unadjusted incident MACE rate was 676.9 events per 10kPYR. 38,330 T2DM patients in the BBCIC DRN had a baseline A1c available, and of those, less than 50% had a follow-up A1c result. CONCLUSIONS: Among patients with T2DM, our observed insulin patterns of use and rates of severe hypoglycemic outcomes and MACE are consistent with other studies. We noted a paucity of A1c results available, which implies that additional data sources may be needed to augment the BBCIC DRN. DISCLOSURES: This study was coordinated and funded by the Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) and represents the independent findings of the BBCIC Insulins Principal Investigator and the BBCIC Insulins Research Team. Lockhart is employed by the BBCIC and the Academy of Managed Care Pharmacy (AMCP). Eichelberger was employed by the BBCIC and AMCP at the time of this study. McMahill-Walraven is employed by Aetna, a CVS Health business. Panozzo, Marshall, and Brown are employed by Harvard Pilgrim Healthcare Institute. Aetna was reimbursed for data and analytic support from Harvard Pilgrim Healthcare Institute and the Reagan Udall Foundation for the U.S. Food and Drug Administration. Aetna receives external funding through research grants and subcontracts with Harvard Pilgrim Healthcare Institute, which are funded by the FDA, NIH, PCORI, BBCIC, Pfizer, and GSK; the Reagan-Udall Foundation for IMEDS; and PCORI for the ADAPTABLE Study. This work was previously presented as a poster at AMCP Nexus 2018; October 22-25, 2018; in Orlando, FL.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Cardiopatias/epidemiologia , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Medicamentos Biossimilares/administração & dosagem , Medicamentos Biossimilares/efeitos adversos , Glicemia/análise , Glicemia/efeitos dos fármacos , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Hemoglobina A Glicada/análise , Cardiopatias/sangue , Cardiopatias/etiologia , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Curta/administração & dosagem , Insulina de Ação Curta/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos de Sulfonilureia/administração & dosagem , Compostos de Sulfonilureia/efeitos adversos , Adulto Jovem
4.
Bioanalysis ; 10(15): 1207-1220, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30062907

RESUMO

AIM: Advances in technology have led to a shift for peptide quantification from traditional ligand-binding assays to LC-MS/MS-based analysis, which presents challenges, in other assay sensitivity, specificity and ruggedness, in addition to lacking of regulatory guidance, especially for the hybrid assay format. Methodology & results: This report communicates a strategy that has been employed in our laboratories for method development and assay validation, and exemplified in a case study of MK-2640, a glucose-responsive insulin, in multiple matrices. Intact MK-2640 was monitored, while immunoaffinity purification and SPE were used to support the rat/dog GLP and clinical studies, respectively. The rationale and considerations behind our approach, as well as the acceptance criteria applied to the assay validation are discussed.


Assuntos
Cromatografia Líquida de Alta Pressão , Insulina/análogos & derivados , Peptídeos/sangue , Espectrometria de Massas em Tandem , Animais , Anticorpos Monoclonais/imunologia , Cromatografia de Afinidade , Cães , Meia-Vida , Humanos , Insulina/análise , Insulina/química , Insulina/farmacologia , Insulina de Ação Prolongada/química , Insulina de Ação Curta/química , Insulinas/química , Insulinas/imunologia , Limite de Detecção , Peptídeos/isolamento & purificação , Peptídeos/farmacocinética , Ratos , Reprodutibilidade dos Testes , Extração em Fase Sólida
5.
Ann Med ; 50(6): 453-460, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30103624

RESUMO

Type 2 diabetes mellitus (T2DM) is a growing problem in the USA, affecting 30.3 million Americans, or 9.4% of the US population. Given that T2DM is a progressive disease, intensification of rapid acting insulin (RAI) to address hyperglycaemia is often required. The American Diabetes Association and the European Association for the Study of Diabetes recommend individualizing the treatment approach to glucose control, considering factors such as age, health behaviours, comorbidities and life expectancy. There are several validated treatment algorithms in the literature, which can be helpful for providing guidance on initiation of RAI while simultaneously considering patient preferences and clinical needs during treatment intensification. This paper provides expert recommendations on prandial insulin regimens and how to use treatment algorithms to promote better glucose control through best practice guidelines. To help patients reach HbA1c targets through treatment intensification, the FullSTEP, SimpleSTEP, ExtraSTEP and AUTONOMY algorithms are discussed in this paper. KEY MESSAGES Clinical inertia should be prevented with timely intensification of therapy when HbA1c levels are greater than 7% (or rising above a patient's individual target) according to national guidelines. Increased personalization in the intensification of T2D treatment is necessary to improve HbA1c targets while addressing risk of hypoglycaemia, concern about weight gain, and overall health goals. Healthcare providers are encouraged to address glycaemic control with a variety of strategies, including prandial insulin, while developing evidence-based treatment plans on the basis of algorithms discussed in the literature.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina de Ação Curta/administração & dosagem , Fatores Etários , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Europa (Continente) , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/normas , Hemoglobina A Glicada/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/normas , Insulina de Ação Curta/efeitos adversos , Insulina de Ação Curta/normas , Guias de Prática Clínica como Assunto , Estados Unidos , Instituições Filantrópicas de Saúde/normas , Ganho de Peso/efeitos dos fármacos
6.
Diabetes Technol Ther ; 20(6): 448-451, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29901406

RESUMO

Treatment with Afrezza® (insulin human) inhalation powder in individuals with type 1 diabetes (T1D) reduces HbA1c levels similar to rapid-acting insulin analogs, but with significantly less hypoglycemia due to its unique time action profile. Examinations of studies of Afrezza pharmacokinetics/pharmacodynamics, relevant clinical trials, and U.S. Food and Drug Administration (FDA) documentation suggest that current FDA-mandated dosing recommendations for initiating Afrezza treatment may not result in optimal glycemic control for individuals with T1D. Recommendations for initiating Afrezza insulin therapy in T1D patients are presented in this article.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina de Ação Curta/uso terapêutico , Administração por Inalação , Glicemia/análise , Humanos , Hipoglicemiantes/administração & dosagem , Insulina de Ação Curta/administração & dosagem
7.
Appl Health Econ Health Policy ; 16(3): 357-366, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29525908

RESUMO

OBJECTIVE: The aim of the present study was to evaluate the cost effectiveness of rapid-acting analog insulin relative to regular human insulin in adults with type 1 diabetes mellitus in Germany. METHODS: The PRIME Diabetes Model, a patient-level, discrete event simulation model, was used to project long-term clinical and cost outcomes for patients with type 1 diabetes from the perspective of a German healthcare payer. Simulated patients had a mean age of 21.5 years, duration of diabetes of 8.6 years, and baseline glycosylated hemoglobin of 7.39%. Regular human insulin and rapid-acting analog insulin regimens reduced glycosylated hemoglobin by 0.312 and 0.402%, respectively. Compared with human insulin, hypoglycemia rate ratios with rapid-acting analog insulin were 0.51 (non-severe nocturnal) and 0.80 (severe). No differences in non-severe diurnal hypoglycemia were modeled. Discount rates of 3% were applied to future costs and clinical benefits accrued over the 50-year time horizon. RESULTS: In the base-case analysis, rapid-acting analog insulin was associated with an improvement in quality-adjusted life expectancy of 1.01 quality-adjusted life-years per patient (12.54 vs. 11.53 quality-adjusted life-years). Rapid-acting analog insulin was also associated with an increase in direct costs of €4490, resulting in an incremental cost-effectiveness ratio of €4427 per quality-adjusted life-year gained vs. human insulin. Sensitivity analyses showed that the base case was driven predominantly by differences in hypoglycemia; abolishing these differences reduced incremental quality-adjusted life expectancy to 0.07 quality-adjusted life-years, yielding an incremental cost-effectiveness ratio of €74,622 per quality-adjusted life-year gained. CONCLUSIONS: Rapid-acting analog insulin is associated with beneficial outcomes in patients with type 1 diabetes and is likely to be considered cost effective in the German setting vs. regular human insulin.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina de Ação Curta/administração & dosagem , Insulina de Ação Curta/economia , Adolescente , Adulto , Criança , Análise Custo-Benefício , Feminino , Alemanha , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Anos de Vida Ajustados por Qualidade de Vida , Adulto Jovem
8.
Georgian Med News ; (274): 92-97, 2018 Jan.
Artigo em Russo | MEDLINE | ID: mdl-29461234

RESUMO

Aim of study‒ estimate the influence of the metformin therapy on the sCD40-ligand and sVE-cadherinlevels among patients with acute myocardial infarction and concomitant type 2 diabetes mellitus. The study included44patients with AMI and type 2 diabetes whichweredividedintotwo groupsdependingonthe glucose lowering drugs they have been taken: I group ‒ 21patients who have been taken metformin; II group ‒ 23patients, who have been taken short-acting insulin. Accordingtotheobtainedresults using of metformin as a glucose lowering drug in comparison with patients who have been taken short-acting insulin causes faster decreasing of the sCD40L level (-29,3% and -24,4% accordingly; р<0,05). Whereas there was no significant differencesin the dynamics of sVE-cadherinlevels (-22,4% and -19,2% accordingly; р>0,05). Positive influence of them et form in on thes CD40-ligand level probably is caused by the inhibition of the Akt-kinase phosphorylation responsible for the activation of the nuclear factor kappa-b which controls expression of the immune response genes, particulary CD40. It leads to the inhibition of the thrombocytes activation and differentiation of the monocytes to the macrophages able to product proatherogenic factors. It was established that metformin therapy among patients with acute myocardial infarction and diabetes mellitus type 2 leads to the faster decreasing of sCD40-ligand in comparison with insulin therapy, which can contribute to the improvemenet of the prognosis in this cohort.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Insulina de Ação Curta/uso terapêutico , Metformina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Antígenos CD/sangue , Antígenos CD/genética , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Plaquetas/patologia , Ligante de CD40/sangue , Ligante de CD40/genética , Caderinas/sangue , Caderinas/genética , Diferenciação Celular/efeitos dos fármacos , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Hemoglobina A Glicada/genética , Hemoglobina A Glicada/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Monócitos/patologia , Infarto do Miocárdio/sangue , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , NF-kappa B , Fosforilação/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
9.
J Diabetes ; 10(2): 94-111, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28581207

RESUMO

A large number of patients with type 2 diabetes (T2D) on basal insulin do not reach their HbA1c goals and require additional therapy to address postprandial hyperglycemia. Guidelines from expert bodies have outlined several approaches to accomplish postprandial glucose (PPG) control, and recent literature suggests several more. This article provides strategies for primary care physicians caring for patients with T2D who do not achieve glycemic control with basal insulin alone. Current treatment guidelines and strategies for improving PPG control are reviewed, including the efficacy, safety, and cost-effectiveness of rapid-acting insulin (RAI) analogs, premixed insulin, glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, and α-glucosidase inhibitors. Other approaches, such as combinations of newer basal insulin plus RAI and a fixed-ratio combination of basal insulin and a GLP-1 RA, are also described.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina de Ação Curta/uso terapêutico , Glicemia/análise , Diabetes Mellitus Tipo 2/complicações , Humanos , Hiperglicemia/etiologia
10.
Postgrad Med ; 129(8): 791-800, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29032696

RESUMO

Worldwide, many people with type 2 diabetes are not at recommended glycemic targets and remain at increased risk of microvascular and macrovascular complications. Reaching recommended glycemic targets requires normalizing both fasting and postprandial glucose (PPG). For some patients, this will require addition of a prandial insulin delivered by injection to control PPG excursions. Evidence from epidemiological studies suggests an association between postprandial hyperglycemia and cardiovascular disease, and thus, expert guidelines recommend that treatment for elevated PPG not be delayed. Indeed, studies have demonstrated that PPG makes the greatest contribution to HbA1c in patients who are approaching, but have not yet reached HbA1c <7.0%. Appropriately timed exposure of the liver to insulin is critical in suppressing hepatic glucose output (and therefore PPG levels) after a meal. Rapid-acting insulin analogs, with their faster onset and shorter duration of action, offer advantages over regular human insulin. Unfortunately, even with improved pharmacokinetic/pharmacodynamic characteristics, rapid-acting insulin analogs are still unable to fully reproduce the rapid release of insulin into the portal circulation and suppression of hepatic glucose output that occurs in the individual without diabetes after starting a meal. The next generation of rapid-acting insulin analogs will have an even more favorable pharmacokinetic profile that should allow patients to further improve glycemic control. Continuous subcutaneous insulin infusion (CSII) represents another option for intensifying therapy and improving postprandial control in some patients, and studies have shown that the benefits are sustainable long-term. However, it is currently unclear which patients stand to benefit the most from the extra expense and complexity of a CSII regimen, and further studies are needed.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Hemoglobina A Glicada/metabolismo , Humanos , Hiperglicemia/fisiopatologia , Sistemas de Infusão de Insulina , Insulina de Ação Curta/uso terapêutico , Período Pós-Prandial/fisiologia
11.
Pharm Res ; 34(11): 2270-2286, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28762200

RESUMO

PURPOSE: Comparison of the dissociation kinetics of rapid-acting insulins lispro, aspart, glulisine and human insulin under physiologically relevant conditions. METHODS: Dissociation kinetics after dilution were monitored directly in terms of the average molecular mass using combined static and dynamic light scattering. Changes in tertiary structure were detected by near-UV circular dichroism. RESULTS: Glulisine forms compact hexamers in formulation even in the absence of Zn2+. Upon severe dilution, these rapidly dissociate into monomers in less than 10 s. In contrast, in formulations of lispro and aspart, the presence of Zn2+ and phenolic compounds is essential for formation of compact R6 hexamers. These slowly dissociate in times ranging from seconds to one hour depending on the concentration of phenolic additives. The disadvantage of the long dissociation times of lispro and aspart can be diminished by a rapid depletion of the concentration of phenolic additives independent of the insulin dilution. This is especially important in conditions similar to those after subcutaneous injection, where only minor dilution of the insulins occurs. CONCLUSION: Knowledge of the diverging dissociation mechanisms of lispro and aspart compared to glulisine will be helpful for optimizing formulation conditions of rapid-acting insulins.


Assuntos
Hipoglicemiantes/química , Insulina Regular Humana/química , Humanos , Injeções Subcutâneas , Insulina/análogos & derivados , Insulina/química , Insulina Aspart/química , Insulina Lispro/química , Insulina de Ação Curta , Cinética , Peso Molecular , Fenóis/química , Agregados Proteicos , Estabilidade Proteica , Relação Estrutura-Atividade , Zinco/química
12.
Diabetes Obes Metab ; 19(12): 1773-1780, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28573681

RESUMO

AIM: To assess the impact of faster aspart vs insulin aspart on long-term clinical outcomes and costs for patients with type 1 diabetes mellitus (T1DM) in the UK setting. METHODS: The QuintilesIMS CORE Diabetes Model was used to project clinical outcomes and costs over patient lifetimes in a cohort with data on baseline characteristics from the "onset 1" trial. Treatment effects were taken from the 26-week main phase of the onset 1 trial, with costs and utilities based on literature review. Future costs and clinical benefits were discounted at 3.5% annually. RESULTS: Projections indicated that faster aspart was associated with improved discounted quality-adjusted life expectancy (by 0.13 quality-adjusted life-years) vs insulin aspart. Improved clinical outcomes resulted from fewer diabetes-related complications and a delayed time to their onset with faster aspart. Faster aspart was found to be associated with reduced costs vs insulin aspart (cost savings of £1715), resulting from diabetes-related complications avoided and reduced treatment costs. CONCLUSIONS: Faster aspart was associated with improved clinical outcomes and cost savings vs insulin aspart for patients with T1DM in the UK setting.


Assuntos
Efeitos Psicossociais da Doença , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Aspart/uso terapêutico , Insulina de Ação Curta/uso terapêutico , Modelos Econômicos , Qualidade de Vida , Biomarcadores/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/economia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Estudos de Coortes , Análise Custo-Benefício , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/economia , Custos Diretos de Serviços , Método Duplo-Cego , Custos de Medicamentos , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/economia , Hiperglicemia/prevenção & controle , Hiperglicemia/terapia , Hipoglicemia/economia , Hipoglicemia/prevenção & controle , Hipoglicemia/terapia , Hipoglicemiantes/economia , Incidência , Insulina Aspart/economia , Insulina de Ação Curta/economia , Pessoa de Meia-Idade , Risco , Reino Unido/epidemiologia
13.
Curr Med Res Opin ; 33(7): 1309-1316, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28393573

RESUMO

OBJECTIVE: To examine the persistence with rapid-acting insulin (RAI) and its association with clinical outcomes among elderly patients with type 2 diabetes (T2D). METHODS: This observational, retrospective cohort study analyzed RAI persistence and its association with change in glycated hemoglobin A1c and risk of severe hypoglycemia among elderly (≥65 years) Medicare beneficiaries with T2D who added RAI to their basal insulin regimen. RESULTS: Among T2D patients with >1 RAI prescriptions (n = 3927), only 21% were persistent. Baseline factors positively associated with RAI persistence (adjusted odds ratio [95% CI]) were: age ≥75 vs. 65-74 years: 1.20 (1.01-1.43); use of ≥3 oral antidiabetes drugs: 1.63 (1.16-2.28); cognitive impairment: 1.34 (1.03-1.73); and A1C >9.0%: 1.58 (1.15-2.17). Elderly T2D patients having emergency department visits (0.73 [0.59-0.91]) and higher RAI out-of-pocket costs (≥$75 vs. $0 - <$6.40: 0.56 [0.44-0.70]) were less likely to be persistent. Persistent RAI users had a significantly higher reduction in A1C (beta coefficient [standard error]): -0.24 (0.10) and lower odds of severe hypoglycemia (adjusted odds ratio [95% CI]): 0.73 (0.53-0.99). CONCLUSION: Among elderly T2D patients, persistence with RAI added to basal insulin was associated with improved glycemic control and lower risk of severe hypoglycemia. Despite treatment effectiveness, RAI persistence was poor and might be improved by reducing RAI out-of-pocket costs.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobina A Glicada , Hipoglicemiantes/administração & dosagem , Insulina de Ação Curta/administração & dosagem , Idoso , Glicemia , Estudos de Coortes , Feminino , Gastos em Saúde , Humanos , Hipoglicemia/epidemiologia , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/uso terapêutico , Masculino , Estudos Retrospectivos , Resultado do Tratamento
14.
Postgrad Med ; 129(4): 436-445, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28294702

RESUMO

OBJECTIVE: To consolidate the evidence from randomized controlled trials evaluating the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as add-on to basal insulin therapy in type 2 diabetes (T2D) patients. RESEARCH DESIGN AND METHODS: We searched the EMBASE® and NCBI PubMed (Medline) databases and relevant congress abstracts for randomized controlled trials evaluating the efficacy and safety of GLP-1 RAs as add-on to basal insulin compared with basal insulin with or without rapid-acting insulin (RAI) through 23 May 2016. The pooled data were analyzed using a random-effects meta-analysis model. A subanalysis was performed for trials investigating basal insulin plus GLP-1 RAs versus basal insulin plus RAI. RESULTS: Of the 2617 retrieved records, 19 randomized controlled trials enrolling 7,053 patients with T2D were included. Compared with basal insulin ± RAI, reduction in glycated hemoglobin (HbA1c) from baseline (difference in means: -0.48% [95% confidence interval (CI), -0.67 to -0.30]; p < 0.0001) and weight loss (-2.60 kg [95% CI, -3.32 to -1.89]; p < 0.0001) were significantly greater with basal insulin plus GLP-1 RA. The subanalysis similarly showed significant results for change in HbA1c from baseline and for weight loss, as well as a significantly lower risk of symptomatic hypoglycemia in patients treated with basal insulin plus GLP-1 RA versus basal insulin plus RAI (odds ratio, 0.52 [95% CI, 0.42 to 0.64]; p < 0.0001). CONCLUSIONS: Addition of GLP-1 RA to basal insulin provided improved glycemic control, led to weight reduction and similar hypoglycemia rates versus an intensified insulin strategy; however, symptomatic hypoglycemia rates were significantly lower when compared with a basal insulin plus RAI.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Hemoglobina A Glicada/análise , Humanos , Insulina de Ação Curta/uso terapêutico
15.
Appl Physiol Nutr Metab ; 42(4): 377-383, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28177738

RESUMO

Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC50 = 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU50 = 3.5% ± 1.6%) or without insulin (GU50 = 7.0% ± 0.5%) in a concentration-dependent manner. Furthermore, sorbitol significantly delayed gastric emptying, accelerated digesta transit, inhibited intestinal glucose absorption, and reduced blood glucose increase in both normoglycemic and type 2 diabetic rats after 1 h of coingestion with glucose. Data of this study suggest that sorbitol exhibited anti-hyperglycemic potentials, possibly via increasing muscle glucose uptake ex vivo and reducing intestinal glucose absorption in normal and type 2 diabetic rats. Hence, sorbitol may be further investigated as a possible anti-hyperglycemic sweetener.


Assuntos
Absorção Fisiológica , Diabetes Mellitus Tipo 2/dietoterapia , Glucose/metabolismo , Absorção Intestinal , Músculo Esquelético/metabolismo , Adoçantes Calóricos/uso terapêutico , Sorbitol/uso terapêutico , Absorção Fisiológica/efeitos dos fármacos , Animais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Carboidratos da Dieta/metabolismo , Esvaziamento Gástrico/efeitos dos fármacos , Trânsito Gastrointestinal/efeitos dos fármacos , Hiperglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Técnicas In Vitro , Insulina de Ação Curta/farmacologia , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Cinética , Masculino , Metformina/farmacologia , Músculo Esquelético/efeitos dos fármacos , Adoçantes Calóricos/efeitos adversos , Adoçantes Calóricos/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Sorbitol/efeitos adversos , Sorbitol/metabolismo
16.
J Manag Care Spec Pharm ; 23(3): 291-298, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28230457

RESUMO

BACKGROUND: Although there are a variety of insulin products and new delivery modalities available, the absence of direct clinical and economic comparisons can make treatment planning and formulary decision making difficult. Direct comparisons between insulin aspart and insulin lispro from a large heterogeneous population are not available. OBJECTIVE: To assess differences in clinical outcomes, medication adherence, utilization, and total health care costs between aspart and lispro and vial versus pen modalities for administering these short-acting insulin analogs. METHODS: This retrospective cohort study used administrative claims data from the Humana Research Database to identify people with type 1 or type 2 diabetes and Medicare or commercial insurance (with medical and pharmacy benefits) who newly initiated rapid-acting insulin between January 1, 2008, and December 31, 2013, and were continuously enrolled during the 12-month baseline and 12-month follow-up periods. Generalized linear models were used to assess differences in costs and utilization. Logistic regression models measured the likelihood of having a hypoglycemic event, worsening diabetes complications, or a change in glycated hemoglobin (A1c). RESULTS: 8,189 patients included in the study were grouped by rapid-acting insulin product (aspart, n = 5,364, and lispro, n = 2,566) and modality (vial, n = 6,135, and pen, n = 2,054). There were no significant differences in the percentage of patients with a hypoglycemic event, new or worsening diabetes complications, or change in A1c, and there were no significant differences in adjusted total health care, medical and pharmacy costs, or emergency department visits between any of the product or modality comparisons. There was a significant difference in mean annual inpatient stays between lispro and aspart (adjusted mean = 2.24, 95% CI = 0.73-6.69, and adjusted mean = 2.65, 95% CI = 0.86-7.86, respectively; P < 0.001) and pen and vial cohorts (adjusted mean = 1.74, 95% CI = 0.56-4.99, and adjusted mean = 3.05, 95% CI = 1.01-9.08, respectively; P < 0.001). Adherence was similar for the lispro and aspart cohorts. Adherence was higher in the pen cohort (as measured by medication possession ratio ≥80%) compared with the vial cohort (adjusted odds ratio = 1.29, 95% CI = 1.12-1.50). CONCLUSIONS: This study provides a comprehensive assessment of outcomes and costs between 2 commonly used rapid-acting insulin products. Overall, there was little differentiation between products, although adherence improved significantly with pen devices. These findings may simplify decisions related to formulary options and choice of therapy. DISCLOSURES: No outside funding supported this study. Racsa and Ellis are employees of Comprehensive Health Insights, a subsidiary of Humana, and Saverno was employed with Comprehensive Health Insights at the time of this study. Meah is an employee of, and owns stock in, Humana. The authors have no financial disclosures or potential conflicts of interest to report. All authors contributed equally to study concept and design, data interpretation, and manuscript preparation. Racsa collected the data.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina de Ação Curta/uso terapêutico , Idoso , Diabetes Mellitus Tipo 1/economia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/economia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Hemoglobina A Glicada/metabolismo , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Hipoglicemiantes/economia , Insulina de Ação Curta/economia , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
Diabetes Metab Syndr ; 11(1): 51-57, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27578616

RESUMO

AIM: Optimal treatment intensification strategies in patients with type-2 diabetes mellitus (T2DM) receiving basal insulin supported oral antidiabetic therapy (BOT) remain controversial. The objective of the present study was to compare outcomes of BOT-intensification by either the uptitration of long-acting insulin glargine or by the immediate addition of a rapid acting insulin analogue (RAIA). METHODS: This was a prospective, observational, 24-week study in T2DM patients with BOT using insulin glargine and baseline glycated hemoglobin (HbA1c) between 7.0 and 8.5%. Patients were stratified by their physicians to one of the following treatment intensification strategies: Basal insulin titration to target with discretionary subsequent addition of RAIA at weeks 12 or 24 (GLAR), or immediate addition of RAIA at baseline (GLARplus). RESULTS: A total of 3266 patients were prescreened of whom 2202 fulfilled the selection criteria. Of these, 1684 patients were documented in the GLAR group and 518 in the GLARplus group. In the GLAR group, in 91 (5.5%) and 21 patients (1.3%) RAIA was added at weeks 12 and 24, respectively. The groups displayed similar baseline characteristics; except, mean diabetes duration was slightly shorter in the GLAR group (8.7 vs. 9.4 years). During the study, insulin glargine dose was increased from 18.7 to 26.4U (plus 7.7U) in GLAR and from 24.9 to 27.3U (plus 2.4U) in GLARplus patients. Mean RAIA dose was 9.6±4.7U at the final visit. After 24 weeks, HbA1c was reduced by 0.8 and 0.9% in the GLAR and GLARplus groups, respectively (both p<0.001). An HbA1c of ≤7.0% was achieved in 49.2% of GLAR and 48.5% of GLARplus patients. In both groups, we observed improvements in cardiovascular risk factors such as lipids and blood pressure. The rates of symptomatic (1.6 vs. 1.7%) and severe (0.18 vs. 0.19%) hypoglycemic episodes were low and comparable in both groups. CONCLUSION: These findings provide evidence that treatment intensification in patients with type 2 diabetes not at glycemic target on BOT with insulin glargine is equally safe and effective using either long-acting insulin titration alone or the addition of a rapid-acting insulin analogue.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/análogos & derivados , Insulina/uso terapêutico , Administração Oral , Adolescente , Adulto , Idoso , Biomarcadores/análise , Glicemia/análise , Diabetes Mellitus Tipo 2/complicações , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/induzido quimicamente , Hipoglicemia/induzido quimicamente , Insulina de Ação Prolongada/uso terapêutico , Insulina de Ação Curta/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Adulto Jovem
18.
Psychiatr Q ; 88(1): 75-91, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27155828

RESUMO

This study investigates the prevalence of anxiety disorder (AD) in Taiwanese patients with type 2 diabetes (T2D). Study participants were identified based on at least one service claim for ambulatory or inpatient care with a principal diagnosis of AD and at least 2 service claims for ambulatory care or one service claim for inpatient care with a principal diagnosis of T2D, as listed in the National Health Insurance database of Taiwan. The prevalence of AD decreased from 13.75 to 11.00 % in patients with T2D, whereas it increased from 4.17 to 6.09 % in the general population during the 2000-2010 period. A high prevalence of AD in patients with T2D was associated with age >30 years, the female sex, living in the northern region, comorbidities of congestive heart failure, peripheral vascular disease, cerebrovascular disease, and depression disorder, and a Charlson participant comorbidity index of ≥1. A low prevalence of AD in patients with T2D was associated with residency in urban areas, the comorbidity of hemiplegia or paraplegia, the usage of metformin and sulfonylureas, and rapid-acting insulin injection therapy. The prevalence of AD was higher in patients with T2D than in the general population. Therefore, more public health emphasis is required for preventing and treating AD in patients with T2D, specifically those with the mentioned risk factors.


Assuntos
Transtornos de Ansiedade/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Transtornos Cerebrovasculares/epidemiologia , Comorbidade , Bases de Dados Factuais , Transtorno Depressivo/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Insuficiência Cardíaca/epidemiologia , Hemiplegia/epidemiologia , Humanos , Hipoglicemiantes/uso terapêutico , Insulina de Ação Curta/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Paraplegia/epidemiologia , Doenças Vasculares Periféricas/epidemiologia , Prevalência , Fatores de Risco , Fatores Sexuais , Compostos de Sulfonilureia/uso terapêutico , Taiwan/epidemiologia , População Urbana , Adulto Jovem
19.
Drugs Aging ; 34(1): 29-38, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27873152

RESUMO

BACKGROUND: Due to population aging, an increasing number of elderly patients with diabetes use insulin. It is therefore important to investigate the characteristics of new insulins in this population. Faster-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with faster absorption. This study investigated the pharmacological properties of faster aspart in elderly subjects with type 1 diabetes mellitus (T1DM). METHODS: In a randomised, double-blind, two-period crossover trial, 30 elderly (≥65 years) and 37 younger adults (18-35 years) with T1DM received single subcutaneous faster aspart or IAsp dosing (0.2 U/kg) and underwent an euglycaemic clamp (target 5.5 mmol/L) for up to 12 h. RESULTS: The pharmacokinetic and pharmacodynamic time profiles were left-shifted for faster aspart versus IAsp. In each age group, onset of appearance occurred approximately twice as fast (~3 min earlier) and early exposure (area under the concentration-time curve [AUC] for serum IAsp from time zero to 30 min [AUCIAsp,0-30 min]) was greater (by 86% in elderly and 67% in younger adults) for faster aspart than for IAsp. Likewise, onset of action occurred 10 min faster in the elderly and 9 min faster in younger adults, and early glucose-lowering effect (AUC for the glucose infusion rate [GIR] from time zero to 30 min [AUCGIR,0-30 min]) was greater (by 109%) for faster aspart than for IAsp in both age groups. Total exposure (AUCIAsp,0-t) and the maximum concentration (C max) for faster aspart were greater (by 30 and 28%, respectively) in elderly than in younger adults. No age group differences were seen for the total (AUCGIR,0-t) or maximum (GIRmax) glucose-lowering effect. CONCLUSION: This study demonstrated that the ultra-fast pharmacological properties of faster aspart are similar in elderly subjects and younger adults with T1DM. ClinicalTrials.gov Identifier: NCT02003677.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Insulina Aspart/farmacocinética , Insulina Aspart/uso terapêutico , Adolescente , Adulto , Idoso , Envelhecimento/sangue , Envelhecimento/efeitos dos fármacos , Glicemia/análise , Química Farmacêutica , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Técnica Clamp de Glucose , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Insulina Aspart/administração & dosagem , Insulina Aspart/química , Insulina de Ação Curta/administração & dosagem , Insulina de Ação Curta/química , Insulina de Ação Curta/farmacocinética , Insulina de Ação Curta/uso terapêutico , Masculino , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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