RESUMEN
Exenatide is used to treat type 2 diabetes mellitus. The current regimen is a 2 mg extended release (ER) weekly injection. The aim of our study was to prove the efficacy of exenatide ER if administered once-monthly. The proposed monthly dose was based on an Excel simulation using pharmacokinetic parameters extracted using Plot Digitizer® (version 2.6.8) from Cirincione et al. (2017), as well as accounting for the exenatide ER formulation characteristics, in vivo and in vitro exenatide stability. A PBPK model of exenatide molecule was developed using (Simcyp® version 19) based on data from in vitro and clinical PK studies. The model was used to confirm the Excel simulation findings of the effectiveness of exenatide ER monthly in maintaining the plasma level above the minimum effective concentration (MEC). Our simulation from Excel and Simcyp® showed that the drug plasma levels of the once monthly ER dose maintained a steady state concentration (Css ) above the MEC. The simulated Excel plasma level ranged from Cmin to Cmax of 60-130ng/L, respectively. The exenatide compound was successfully modeled and used to predict the Css of the ER monthly dose. The Simcyp® simulated Css of the ER was 117 ng/L. A monthly exenatide ER dose provides a plasma level within the therapeutic range. This new proposed dose has a significant pharmacoeconomic benefit and could well improve patient adherence.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Exenatida/administración & dosificación , Hipoglucemiantes/administración & dosificación , Modelos Biológicos , Análisis Costo-Beneficio , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/economía , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/economía , Esquema de Medicación , Exenatida/sangre , Exenatida/economía , Exenatida/farmacocinética , Humanos , Hipoglucemiantes/sangre , Hipoglucemiantes/economía , Hipoglucemiantes/farmacocinéticaRESUMEN
OBJECTIVES: Outcomes-based contracts tie rebates and discounts for expensive drugs to outcomes. The objective was to estimate the utility of outcomes-based contracts for diabetes medications using real-world data and to identify methodologic limitations of this approach. METHODS: A population-based cohort study of adults newly prescribed a medication for diabetes with a publicly announced outcomes-based contract (ie, exenatide microspheres ["exenatide"], dulaglutide, or sitagliptin) was conducted. The comparison group included patients receiving canagliflozin or glipizide. The primary outcome was announced in the outcomes-based contract: the percentage of adults with a follow-up hemoglobin A1C <8% up to 1 year later. Secondary outcomes included the percentage of patients diagnosed with hypoglycemia and the cost of a 1-month supply. RESULTS: Thousands of adults newly filled prescriptions for exenatide (n = 5079), dulaglutide (n = 6966), sitagliptin (n = 40 752), canagliflozin (n = 16 404), or glipizide (n = 59 985). The percentage of adults subsequently achieving a hemoglobin A1C below 8% ranged from 83% (dulaglutide, sitagliptin) to 71% (canagliflozin). The rate of hypoglycemia was 25 per 1000 person-years for exenatide, 37 per 1000 person-years for dulaglutide, 28 per 1000 person-years for sitagliptin, 18 per 1000 person-years for canagliflozin, and 34 per 1000 person-years for glipizide. The cash price for a 1-month supply was $847 for exenatide, $859 for dulaglutide, $550 for sitagliptin, $608 for canagliflozin, and $14 for glipizide. CONCLUSION: Outcomes-based pricing of diabetes medications has the potential to lower the cost of medications, but using outcomes such as hemoglobin A1C may not be clinically meaningful because similar changes in A1C can be achieved with generic medications at a far lower cost.
Asunto(s)
Contratos/economía , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Evaluación de Resultado en la Atención de Salud/métodos , Anciano , Canagliflozina/administración & dosificación , Canagliflozina/economía , Estudios de Cohortes , Diabetes Mellitus Tipo 2/economía , Exenatida/administración & dosificación , Exenatida/economía , Femenino , Estudios de Seguimiento , Glipizida/administración & dosificación , Glipizida/economía , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/análogos & derivados , Péptidos Similares al Glucagón/economía , Humanos , Hipoglucemiantes/economía , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/economía , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/economía , Fosfato de Sitagliptina/administración & dosificación , Fosfato de Sitagliptina/economíaRESUMEN
INTRODUCTION: Once-weekly semaglutide 1 mg is a novel glucagon-like peptide 1 receptor agonist (GLP-1 RA) that, in the SUSTAIN clinical trials, has demonstrated greater reductions in glycated haemoglobin (HbA1c) and body weight than the other GLP-1 RAs exenatide extended-release (ER) 2 mg, dulaglutide 1.5 mg and liraglutide 1.2 mg. The aim of this analysis was to evaluate the relative cost of control of achieving treatment goals in people with type 2 diabetes (T2D) treated with once-weekly semaglutide versus exenatide ER, dulaglutide and liraglutide from a UK perspective. METHODS: Proportions of patients reaching HbA1c targets (< 7.0% and < 7.5%), weight loss targets (≥ 5% reduction in body weight) and composite endpoints (HbA1c < 7.0% without weight gain or hypoglycaemia; reduction in HbA1c of ≥ 1% and weight loss of ≥ 5%) were obtained from the SUSTAIN clinical trials. Annual per patient treatment costs were based on wholesale acquisition costs from July 2019 in the UK. Cost of control was calculated by plotting relative treatment costs against relative efficacy. RESULTS: The annual per patient cost was similar for all GLP-1 RAs. Once-weekly semaglutide was superior to exenatide ER, dulaglutide and liraglutide in bringing patients to HbA1c and weight loss targets, and to composite endpoints. When looking at the composite endpoint of HbA1c < 7.0% without weight gain or hypoglycaemia, exenatide ER, dulaglutide and liraglutide were 50.0%, 21.6% and 51.3% less efficacious in achieving this, respectively, than once-weekly semaglutide. Consequently, the efficacy-to-cost ratios for once-weekly semaglutide were superior to all comparators in bringing patients to all endpoints. CONCLUSIONS: The present study showed that once-weekly semaglutide offers superior cost of control versus exenatide ER, dulaglutide and liraglutide in terms of achieving clinically relevant, single and composite endpoints. Once-weekly semaglutide 1 mg would therefore represent good value for money in the UK setting.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptidos Similares al Glucagón/economía , Péptidos Similares al Glucagón/uso terapéutico , Hipoglucemiantes/economía , Hipoglucemiantes/uso terapéutico , Peso Corporal , Análisis Costo-Beneficio , Esquema de Medicación , Exenatida/economía , Exenatida/uso terapéutico , Femenino , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/análogos & derivados , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/economía , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Liraglutida/economía , Liraglutida/uso terapéutico , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/economía , Proteínas Recombinantes de Fusión/uso terapéutico , Reino Unido , Aumento de PesoRESUMEN
OBJECTIVE: To compare medical resource use, costs, and health utilities for 14,752 patients with type 2 diabetes who were randomized to once-weekly exenatide (EQW) or placebo in addition to usual diabetes care in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). RESEARCH DESIGN AND METHODS: Medical resource use data and responses to the EuroQol 5-Dimension (EQ-5D) instrument were collected at baseline and throughout the trial. Medical resources and medications were assigned values by using U.S. Medicare payments and wholesale acquisition costs, respectively. Secondary analyses used English costs. RESULTS: Patients were followed for an average of 3.3 years, during which time those randomized to EQW experienced 0.41 fewer inpatient days (7.05 vs. 7.46 days; relative rate ratio 0.91; P = 0.05). Rates of outpatient medical visits were similar, as were total inpatient and outpatient costs. Mean costs for nonstudy diabetes medications over the study period were â¼$1,600 lower with EQW than with placebo (P = 0.01). Total within-study costs, excluding study medication, were lower in the EQW arm than in the placebo arm ($28,907 vs. $30,914; P ≤ 0.01). When including the estimated cost of EQW, total mean costs were significantly higher in the EQW group than in the placebo group ($42,697 vs. $30,914; P < 0.01). With English costs applied, mean total costs, including exenatide costs, were £1,670 higher in the EQW group than the placebo group (£10,874 vs. £9,204; P < 0.01). There were no significant differences in EQ-5D health utilities between arms over time. CONCLUSIONS: Medical costs were lower in the EQW arm than the placebo arm, but total costs were significantly higher once the cost of branded exenatide was incorporated.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Exenatida/uso terapéutico , Costos de la Atención en Salud , Recursos en Salud , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/economía , Enfermedades Cardiovasculares/epidemiología , Causas de Muerte , Diabetes Mellitus Tipo 2/economía , Diabetes Mellitus Tipo 2/epidemiología , Angiopatías Diabéticas/economía , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/prevención & control , Exenatida/economía , Femenino , Estudios de Seguimiento , Costos de la Atención en Salud/estadística & datos numéricos , Recursos en Salud/economía , Recursos en Salud/estadística & datos numéricos , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Humanos , Hipoglucemiantes/economía , Hipoglucemiantes/uso terapéutico , Incidencia , Análisis de Intención de Tratar , Masculino , Medicare/economía , Medicare/estadística & datos numéricos , Persona de Mediana Edad , Reino Unido/epidemiología , Estados Unidos/epidemiologíaRESUMEN
INTRODUCTION: The SUSTAIN 3 and 7 clinical trials compared the efficacy and safety of once-weekly semaglutide relative to exenatide extended-release (ER) and dulaglutide, respectively, in the treatment of patients with type 2 diabetes (T2D). The trials included a series of clinically relevant single and composite endpoints focused on improving glycemic control and reducing body weight, while avoiding hypoglycemia. The present study combined SUSTAIN 3 and 7 outcomes with short-term treatment costs to evaluate the relative cost of control of once-weekly semaglutide versus exenatide ER and dulaglutide. METHODS: Proportions of patients reaching three endpoints were taken from SUSTAIN 3 and 7 for comparisons with exenatide ER and dulaglutide, respectively. The endpoints investigated were HbA1c < 7.0%, HbA1c < 7.0% without hypoglycemia or weight gain, and a ≥ 1.0% HbA1c reduction with ≥ 5.0% weight loss. Annual per patient treatment costs were based on US wholesale acquisition costs from July 2018. Relative cost of control was calculated by plotting the ratio of the treatment costs and the ratio of the proportions of patients reaching each endpoint on the cost-efficacy plane. RESULTS: Once-weekly semaglutide 0.5 mg and 1.0 mg were most effective at bringing patients to each of the three endpoints across both SUSTAIN trials. The efficacy-to-cost ratios for once-weekly semaglutide 0.5 mg and 1.0 mg were also superior to all comparators when assessing both the single endpoint of HbA1c < 7.0% and the two composite endpoints including weight loss and hypoglycemia. CONCLUSIONS: The present study showed that once-weekly semaglutide 0.5 mg and 1.0 mg offer superior cost of control versus exenatide ER and dulaglutide in terms of achieving single and composite endpoints, based on an analysis of retrieved dropout data. Once-weekly semaglutide 0.5 mg and 1.0 mg would therefore represent good value for money in the USA, particularly in the attainment of multi-model T2D treatment goals. FUNDING: Novo Nordisk A/S.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Exenatida/uso terapéutico , Péptidos Similares al Glucagón/análogos & derivados , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Peso Corporal , Diabetes Mellitus Tipo 2/economía , Diabetes Mellitus Tipo 2/metabolismo , Esquema de Medicación , Exenatida/economía , Femenino , Péptidos Similares al Glucagón/economía , Péptidos Similares al Glucagón/uso terapéutico , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/economía , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/economía , Pérdida de PesoRESUMEN
AIMS: To compare healthcare utilization and costs between patients with type 2 diabetes (T2D) treated with exenatide (Bydureon) once weekly (EQW) and patients treated with insulin glargine (IG). MATERIALS AND METHODS: Using the MarketScan Commercial and Medicare Supplemental databases, we conducted a retrospective cohort study of adult US patients with claim with a diagnosis of T2D, initiating EQW or IG from February 1, 2012 to June 30, 2014 (first claim = index date). All-cause and diabetes-related utilization and costs were measured during the 12 months after the index date. EQW patients were matched 1:1 to IG patients, using propensity scores. Logistic and ordinary least-squares regression models were fit to model differences between the matched cohorts. RESULTS: There were 7749 EQW patients matched to 7749 IG patients. EQW patients had significantly (P < .05) lower odds of all-cause inpatient (IP) admissions (odds ratio = 0.737 [95% confidence interval, 0.661, 0.822]), diabetes-related IP admissions (0.720 [95% confidence interval, 0.635, 0.815]) and diabetes-related IP admissions or emergency room visits (0.778 [95% confidence interval, 0.713, 0.847]). EQW patients had significantly (P < .05) lower all-cause (cost difference = -113 USD [95% confidence interval, -120 USD, -106 USD]) and diabetes-related (-806 USD [95% confidence interval, -871 USD, -746 USD]) medical costs, and had significantly (P < .05) higher all-cause total costs (ie, medical plus pharmacy) (3228 USD [95% confidence interval, 3110 USD, 3367 USD]), diabetes-related total costs (1951 USD [95% confidence interval, 1873 USD, 2036 USD]), all-cause pharmacy costs (2792 USD [95% confidence interval, 2700 USD, 2928 USD]) and diabetes-related pharmacy costs (1923 USD [95% confidence interval, 1890 USD, 1957 USD]) than those of IG patients. CONCLUSIONS: Among adults with T2D, EQW initiators had lower odds of IP admission and lower medical costs in the 12 months after initiation than IG initiators. Higher total costs in EQW patients were driven by greater pharmacy costs.