Search

Introduction: Empagliflozin demonstrates promising clinical benefits in patients with heart failure (HF). While an early study demonstrates that empagliflozin is cost-effective for treating HF patients with reduced ejection fraction (HFrEF) in Malaysia, its cost-effectiveness for HF with ejection fraction (EF)>40% remains unclear. Therefore, the current study aimed to assess the cost-effectiveness of adding empagliflozin to the standard of care (SoC) for HF patients with EF>40% from the perspective of Malaysian healthcare system. Subsequently, the results were consolidated with the findings for HFrEF to evaluate the cost-effectiveness of empagliflozin when used for all HF patients in Malaysia, irrespective of EF., Methods: A cost-utility analysis was performed using a validated Markov model, which modelled a cohort of adult patients through health states related to symptom severity and functional impairment, to estimate costs and quality-adjusted life-years (QALYs). The influence of model inputs and assumptions, sensitivity, scenario, and subgroup analyses were explored. All costs were expressed in 2022 Malaysian ringgits (RM). Costs and QALYs were discounted at an annual rate of 3.0% as per local pharmacoeconomic guideline., Results: The base-case incremental cost-effectiveness ratio (ICER) for HF patients with EF>40% was RM 40,454 per QALY gained. At a cost-effectiveness threshold of RM 47,439/QALY gained, empagliflozin was cost-effective in 57% of replications. The model outcomes were sensitive to inputs related to the treatment effect of empagliflozin in reducing HF-related hospitalisation and cardiovascular mortality, and empagliflozin cost. For the overall HF population, the ICER was RM 29,463/QALY gained., Conclusion: The findings suggest that empagliflozin is a cost-effective treatment option for the Malaysian HF population, including those with EF>40%. As such, the intervention warrants consideration by the Malaysian healthcare provider to mitigate the burden of HF and address the unmet needs of the EF>40% population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Cardiovascular-kidney-metabolic (CKM) syndrome is highly prevalent in the US Medicare population and is projected to increase further. Sodium-glucose co-transporter 2 inhibitors have indications in chronic kidney disease (CKD), heart failure (HF), and type 2 diabetes (T2D), providing protective efficacy across conditions within CKM syndrome. The objective of this study was to develop a model to extrapolate key outcomes observed in pivotal clinical trials to the US Medicare population, and to assess the potential direct cost offsets associated with dapagliflozin therapy., Methods: All US 2022 Medicare beneficiaries (≥ 65 years of age) eligible to receive dapagliflozin were estimated according to drug label indication and Medicare enrollment and claims data. Incidence of key outcomes from the dapagliflozin clinical program were modelled over a 4-year time horizon based on patient-level data with CKD, HF, and T2D. Published cost data of relevant clinical outcomes were used to calculate direct medical care cost-offset associated with treatment with dapagliflozin., Results: In a population of 13.1 million patients with CKM syndrome, treatment with dapagliflozin in addition to historical standard of care (hSoC) versus hSoC alone led to fewer incidents of HF-related events (hospitalization for HF, 613,545; urgent HF visit, 98,896), renal events (kidney failure, 285,041; ≥ 50% sustained decline in kidney function, 375,137), and 450,355 fewer deaths (of which 225,346 and 13,206 incidences of cardiovascular and renal death were avoided). In total this led to medical care cost offsets of $99.3 billion versus treatment with hSoC only (dapagliflozin plus hSoC, $310.3 billion; hSoC, $211.0 billion)., Conclusion: By extrapolating data from trials across multiple indications within CKM syndrome, this broader perspective shows that considerable medical care cost offsets may result through attenuated incidence of clinical events in CKD, T2D, and HF populations if treated with dapagliflozin in addition to hSoC over a 4-year time horizon. Graphical abstract available for this article., (© 2024. The Author(s).)

Aim: In 2022, in Italy, general practitioners (GPs) have been allowed to prescribe SGLT2i in Type 2 Diabetes (T2D) under National Health Service (NHS) reimbursement. In the pivotal clinical trial named DECLARE-TIMI 58, dapagliflozin reduced the risk of hospitalization for heart failure, CV death and kidney disease progression compared to placebo in a population of T2D patients. This study evaluated the health and economic impact of dapagliflozin for T2D patients who had or were at risk for atherosclerotic cardiovascular disease in the Italian GPs setting., Methods: A budget impact model was developed to assess the health and economic impact of introducing dapagliflozin in GPs setting. The analysis was conducted by adopting the Italian NHS perspective and a 3-year time horizon. The model estimated and compared the health outcomes and direct medical costs associated with a scenario with dapagliflozin and other antidiabetic therapies available for GPs prescription (scenario B) and a scenario where only other antidiabetic therapies are available (scenario A). Rates of occurrence of cardiovascular and renal complications as well as adverse events were captured from DECLARE-TIMI 58 trial and the literature, while cost data were retrieved from the Italian tariff and the literature. One-way sensitivity analyses were conducted to test the impact of model parameters on the budget impact., Results: The model estimated around 442.000 patients eligible for the treatment with dapagliflozin in the GPs setting for each simulated year. The scenario B compared to scenario A was associated with a reduction in the occurrence of cardiovascular and renal complication (-1.83%) over the 3 years simulated. Furthermore, the scenario A allowed for an overall cost saving of 102,692,305€: 14,521,464€ in the first year, 33,007,064€ in the second and 55,163,777€ in the third. The cost of cost of drug acquisition, the probability of cardiovascular events and the percentage of patients potentially eligible to the treatment were the factor with largest impact on the results., Conclusions: The use of dapagliflozin in GPs setting reduce the number of CVD events, kidney disease progression and healthcare costs in Italy. These data should be considered to optimize the value produced for the T2D patients who had or were at risk for atherosclerotic cardiovascular disease., (© 2024. The Author(s).)

Background: Guideline Directed Medical Therapy (GDMT) has been revolutionary in improving outcomes of heart failure patients. However, with the addition of more medication classes, the annual cost of these medications on the US healthcare system needs further evaluation., Objectives: We aim to evaluate the trend of annual cost of GDMT from 2013 to 2021 using the Medicare-part D Database., Methods: Using Medicare Part D database (2013-2021), we determined the number of beneficiaries receiving these drugs, the total number of 30-day fills for each medication, and the total annual spending on these medications. Linear regression was used to analyze data using Python Programming Language. P value of less than 0.05 was considered to be statistically significant., Results: The estimated annual Medicare- part D spending on empagliflozin had a 50 % increase in cost between 2020 and 2021, which could be attributed to its FDA approval for heart failure with reduced ejection fraction. Empagliflozin cost Medicare 3.73 billion USD in 2021 alone. In addition, sacubitril-valsartan had a strong trajectory since its introduction to the market in 2015. Since its approval in July 2015, it cost Medicare 4.51 billion USD. The Mineralocorticoid Receptor Antagonist class was the least costly class of GDMT., Conclusion: The rise in the cost of GDMT is not proportionate amongst the different classes of GDMT. Newer classes of medications cast a significant cost on Medicare in recent years., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: One in 7 adults have chronic kidney disease (CKD), which is associated with high morbidity and mortality and substantial health care costs, especially in more advanced disease. Our data from a US commercial payer show rising per-member-per-year costs for renal and cardiac complications associated with CKD., Objective: To predict the clinical and economic impact of treatment with or without dapagliflozin from the perspective of a US commercial payer using a cost-offset model (COM)., Methods: The COM used real-world cost and member count data from a US employer-sponsored commercial payer and results of the double-blind, randomized, phase 3 Dapagliflozin and Prevention of Adverse Outcomes in CKD clinical trial (NCT03036150) to predict the incidence of clinical events, including a greater than or equal to 50% decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease, and hospitalization for heart failure, and their associated costs over a 3-year period. The COM compared a hypothetical scenario of the experience with or without dapagliflozin in members with CKD stages 2-4, aged younger than 65 years., Results: In the simulated populations of 130 members, the COM projected 9 events of a greater than or equal to 50% decline in estimated glomerular filtration rate for the experience with dapagliflozin vs 15 events for the experience without dapagliflozin (6 fewer events; number needed to treat [NNT] = 20, amounting to estimated cumulative cost offsets of $0.57 million [M] over a 3-year period). The COM projected similar results for end-stage kidney disease (8 events with dapagliflozin vs 14 events without dapagliflozin; NNT = 24, amounting to $1.92 M in cumulative cost offsets) and for hospitalization for heart failure (13 events with dapagliflozin vs 33 events without dapagliflozin; NNT = 7, amounting to $0.79 M in cumulative cost offsets). These projections translated to total mean, cumulative cost offsets of $3.89 M for all clinical events evaluated over the 3-year period (36.6% reduction with dapagliflozin vs without dapagliflozin), and net mean, cumulative cost offsets of $2.58 M over the 3-year period (24.2% reduction with dapagliflozin vs without dapagliflozin) after factoring in a discounted wholesale acquisition cost for dapagliflozin expenditure ($1.31 M over 3 years). Thus, the net mean, cumulative cost offsets were $19,843 per member over 3 years, representing a 197% return on investment for dapagliflozin expenditure., Conclusions: Results of our COM suggest that dapagliflozin can reduce clinical events and their associated costs over a 3-year period when compared with a scenario without dapagliflozin. Cost offsets increased with each year, indicating that US commercial payers can substantially reduce costs associated with CKD morbidity and mortality.

Aim: To assess the cost-effectiveness of dapagliflozin in addition to usual care, compared with usual care alone, in a large population of patients with heart failure (HF), spanning the full range of left ventricular ejection fraction (LVEF)., Methods and Results: Patient-level data were pooled from HF trials (DAPA-HF, DELIVER) to generate a population including HF with reduced, mildly reduced and preserved LVEF, to increase statistical power and enable exploration of interactions among LVEF, renal function and N-terminal pro-B-type natriuretic peptide levels, as they are relevant determinants of health status in this population. Survival and HF recurrent event risk equations were derived and applied to a lifetime horizon Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire total symptom score quartiles; costs and utilities were in the UK setting. The base case incremental cost-effectiveness ratio (ICER) was £6470 per quality-adjusted life year (QALY) gained, well below the UK willingness-to-pay (WTP) threshold of £20 000/QALY gained. In interaction sensitivity analyses, the highest ICER was observed for elderly patients with preserved LVEF (£16 624/QALY gained), and ranged to a region of dominance (increased QALYs, decreased costs) for patients with poorer renal function and reduced/mildly reduced LVEF. Results across the patient characteristic interaction plane were mostly between £5000 and £10 000/QALY gained., Conclusions: Dapagliflozin plus usual care, versus usual care alone, yielded results well below the WTP threshold for the UK across a heterogeneous population of patients with HF including the full spectrum of LVEF, and is likely a cost-effective intervention., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: The sodium-glucose co-transporter-2 inhibitor empagliflozin was approved for treatment of adults with chronic kidney disease (CKD) on the basis of its demonstrated ability to slow CKD progression and reduce the risk of cardiovascular death. This analysis was performed to assess the cost-effectiveness of empagliflozin plus standard of care (SoC) vs SoC alone in the treatment of CKD in the UK., Methods: A comprehensive, patient-level CKD progression model that simulates the evolution of risk factors for disease progression based on CKD-specific equations and clinical data was used to project a broad range of CKD-related complications. Patient baseline characteristics, distribution across Kidney Disease Improving Global Outcomes (KDIGO) health states, and changes in estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (uACR), and other parameters while on treatment were derived from the EMPA-KIDNEY trial. UK cost and utilities/disutilities were sourced from the literature. Univariate and probabilistic sensitivity analyses were conducted. Annual discounting of 3.5% was applied on costs and outcomes., Results: Over a 50-year horizon, SoC resulted in per-patient costs, life years, and QALYs of £95,930, 8.55, and 6.28, respectively. Empagliflozin plus SoC resulted in an incremental gain in life years (+1.04) and QALYs (+0.84), while decreasing per-patient costs by £6,019. Empagliflozin was more effective and less costly (dominant) with a net monetary benefit of £22,849 at the willingness-to-pay threshold of £20,000. Although treatment cost was higher for empagliflozin, this was more than offset by savings in kidney replacement therapy. Empagliflozin remained highly cost-effective in patients with and without diabetes, and across scenario and sensitivity analyses., Limitations: This analysis is limited by reliance on short-term clinical trial data and by uncertainties in modelling CKD progression., Conclusions: Empagliflozin as an add-on to SoC for treatment of adults with CKD represents cost-effective use of UK National Health Service (NHS) resources.

Background and Objectives: Nearly one in ten individuals in South-East Asia are estimated to be affected by chronic kidney disease (CKD). The burden of end-stage kidney disease is significant and can be heavy on the healthcare system. The recent EMPA-KIDNEY trial demonstrated a significant reduction in the risk of kidney disease progression or cardiovascular death in patients with CKD with a broad range of kidney function using add-on empagliflozin versus standard of care (SoC) alone. The objective of this study was to estimate the economic benefit of empagliflozin for patients with CKD in Malaysia, Thailand and Vietnam., Methods: An individual patient level simulation model with an annual cycle that estimates the progression of kidney function and associated risk-factors was employed. Local costs and mortality rates were estimated from a wide range of published literature. A healthcare perspective was used over a 50-year time horizon., Results: The use of add-on empagliflozin versus SoC alone was found to be cost-saving in Malaysia and Thailand and cost-effective (ICER: 77,838,407 Vietnam Dong/QALY vs. a willingness to pay threshold of 96,890,026/QALY) in Vietnam. The bulk of the costs avoided over a lifetime is derived from the prevention or delay of dialysis initiation or kidney transplant - the cost offsets were nearly twice the additional treatment cost. The results were similar in patients with and without diabetes and across broad range of albuminuria., Conclusions: The use of add-on empagliflozin in a broad population of patients with CKD is expected to be cost-saving in Malaysia and Thailand and cost-effective in Vietnam and will help alleviate the increasing burden of CKD in the region.

Background: With emerging evidence on the efficacy of adding dapagliflozin to standard care for patients with heart failure with reduced ejection fraction (HFrEF), this study assessed the cost-effectiveness of add-on dapagliflozin to standard care versus standard care alone for HFrEF from the perspective of healthcare systems in the Asia-Pacific region., Methods: A Markov model was applied to project the outcomes of treatment in terms of lifetime medical cost and quality-adjusted life-years. The transition probabilities between health states in the model were obtained from the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction trial. Country-specific costs and utilities were extracted for modeling. The incremental cost-effectiveness ratio against a country-specific willingness-to-pay threshold was applied to determine the cost-effectiveness of treatment. A series of sensitivity analyses were performed to ensure the robustness of the study results. Costs are presented in 2020 United States dollars., Results: The incremental cost-effectiveness ratios for add-on dapagliflozin versus standard care alone were $5277, $9980, $12,305, $16,705, and $23,227 per quality-adjusted life-year gained in Korea, Australia, Taiwan, Japan, and Singapore, respectively. When using add-on dapagliflozin to standard care versus standard care alone, ~ 100% of simulations were cost-effective at a willingness-to-pay threshold of one gross domestic product per capita of the given Asia-Pacific country; however, the probability of being cost-effective for using add-on dapagliflozin decreased when the time horizon for simulation was restricted to 18 months and when the cardiovascular mortality for the two treatments (43.8% and 33.0%, respectively) was assumed to be the same. The cost-effectiveness results were most sensitive to cardiovascular mortality of treatment., Conclusions: Adding dapagliflozin to standard care is cost-effective for HFrEF in healthcare systems in the Asia-Pacific region, which supports the rational use of dapagliflozin for HFrEF in this region., (© 2021. The Author(s).)

Importance: In the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial, dapagliflozin was shown to reduce cardiovascular mortality and hospitalizations due to heart failure while improving patient-reported health status. However, the cost-effectiveness of adding dapagliflozin therapy to standard of care (SOC) is unknown., Objective: To estimate the cost-effectiveness of dapagliflozin therapy among patients with chronic heart failure with reduced ejection fraction (HFrEF)., Design, Setting, and Participants: This Markov cohort cost-effectiveness model used estimates of therapy effectiveness, transition probabilities, and utilities from the DAPA-HF trial and other published literature. Costs were derived from published sources. Patients with HFrEF included subgroups based on diabetes status and health status impairment due to heart failure. We compiled parameters from the literature including DAPA-HF, on which our model is based, and many other sources from December 2019 to February 27, 2021. We performed our analysis in February 2021., Exposures: Dapagliflozin or SOC., Main Outcomes and Measures: Hospitalizations for heart failure, life-years, quality-adjusted life-years (QALYs), costs, and the cost per QALY gained (incremental cost-effectiveness ratio)., Results: In the model, dapagliflozin therapy yielded a mean of 0.78 additional life-years and 0.46 additional QALYs compared with SOC at an incremental cost of $38 212, resulting in a cost per QALY gained of $83 650. The cost per QALY was similar for patients with or without diabetes and for patients with mild or moderate impairment of health status due to heart failure. The cost-effectiveness was most sensitive to estimates of the effect on mortality and duration of therapy effectiveness. If the cost of dapagliflozin decreased from $474 to $270 (43% decline), the cost per QALY gained would drop below $50 000., Conclusions and Relevance: These findings suggest that dapagliflozin provides intermediate value compared with SOC, based on American College of Cardiology/American Heart Association benchmarks. Additional data regarding the magnitude of mortality reduction would improve the precision of cost-effectiveness estimates.

BACKGROUND: Oral semaglutide is the first orally administered glucagon-like peptide-1 receptor agonist (GLP-1RA) approved by the FDA. Clinical trials found that oral semaglutide 14 mg had a greater reduction in hemoglobin A1c (A1c) compared with empagliflozin 25 mg and sitagliptin 100 mg and was noninferior to liraglutide 1.8 mg. However, US cost-effectiveness data for oral semaglutide are limited and do not consider the costs of adverse events. OBJECTIVE: To assess the short-term cost-effectiveness of oral semaglutide compared with empagliflozin, sitagliptin, and liraglutide in patients with type 2 diabetes. METHODS: A decision analysis over a 52-week time horizon was used to evaluate the incremental cost-effectiveness of oral semaglutide vs empagliflozin, sitagliptin, and liraglutide from a US health care payer's perspective. Data on efficacy, adverse events, and discontinuation were derived from 52-week data from phase 3, head-to-head clinical trials (PIONEER 2, 3, and 4). Costs included drug and administration cost and treatment of gastrointestinal adverse events. Incremental cost-effectiveness ratios (ICERs) were calculated as the difference in cost over the difference in A1c reduction between oral semaglutide and comparators. RESULTS: In the base-case analysis, 52-week treatment costs with oral semaglutide were $2,660 and $3,104 higher and $2,337 less than empagliflozin, sitagliptin, and liraglutide, respectively. Incremental (greater) A1c reductions were seen with oral semaglutide at 0.40%, 0.50%, and 0.30% vs empagliflozin, sitagliptin, and liraglutide, respectively. ICERs per 1% reduction in A1c for oral semaglutide were $6,650 and $6,207 vs empagliflozin and sitagliptin, respectively. Oral semaglutide was dominant vs liraglutide (ICER of -$7,790). CONCLUSIONS: Oral semaglutide was dominant relative to liraglutide, offering a cost-saving GLP-1RA oral alternative. While there is not a recognized willingness-to-pay threshold for a 1% reduction in A1c, oral semaglutide may be cost-effective relative to empagliflozin and sitagliptin if a decision maker's willingness-to-pay threshold exceeds $6,650 and $6,207, respectively. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest to declare.

Importance: Heart failure with reduced ejection fraction produces substantial morbidity, mortality, and health care costs. Dapagliflozin is the first sodium-glucose cotransporter 2 inhibitor approved for the treatment of heart failure with reduced ejection fraction., Objective: To examine the cost-effectiveness of adding dapagliflozin to guideline-directed medical therapy for heart failure with reduced ejection fraction in patients with or without diabetes., Design, Setting, and Participants: This economic evaluation developed and used a Markov cohort model that compared dapagliflozin and guideline-directed medical therapy with guideline-directed medical therapy alone in a hypothetical cohort of US adults with similar clinical characteristics as participants of the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction (DAPA-HF) trial. Dapagliflozin was assumed to cost $4192 annually. Nonparametric modeling was used to estimate long-term survival. Deterministic and probabilistic sensitivity analyses examined the impact of parameter uncertainty. Data were analyzed between September 2019 and January 2021., Main Outcomes and Measures: Lifetime incremental cost-effectiveness ratio in 2020 US dollars per quality-adjusted life-year (QALY) gained., Results: The simulated cohort had a starting age of 66 years, and 41.8% had diabetes at baseline. Median (interquartile range) survival in the guideline-directed medical therapy arm was 6.8 (3.5-11.3) years. Dapagliflozin was projected to add 0.63 (95% uncertainty interval [UI], 0.25-1.15) QALYs at an incremental lifetime cost of $42 800 (95% UI, $37 100-$50 300), for an incremental cost-effectiveness ratio of $68 300 per QALY gained (95% UI, $54 600-$117 600 per QALY gained; cost-effective in 94% of probabilistic simulations at a threshold of $100 000 per QALY gained). Findings were similar in individuals with or without diabetes but were sensitive to drug cost., Conclusions and Relevance: In this study, adding dapagliflozin to guideline-directed medical therapy was projected to improve long-term clinical outcomes in patients with heart failure with reduced ejection fraction and be cost-effective at current US prices. Scalable strategies for improving uptake of dapagliflozin may improve long-term outcomes in patients with heart failure with reduced ejection fraction.

Aim: When glycaemic control for people with type 2 diabetes is not achieved with metformin and sulfonylurea alone, adding another oral anti-diabetes drug, such as a sodium-glucose co-transporter 2 (SGLT2) or dipeptidyl peptidase-4 (DPP-4) inhibitor, is an alternative to starting insulin. The aim of this study is to determine the cost-effectiveness of dapagliflozin (an SGLT2 inhibitor) compared with DPP-4 inhibitors when added to metformin and sulfonylurea in people with type 2 diabetes in the Netherlands., Methods: A cost-utility analysis is performed using the Cardiff diabetes model, a fixed-time increment stochastic simulation model informed by 'United Kingdom Prospective Diabetes Study 68' risk equations. The base-case analysis uses a 40-year time horizon, a Dutch societal perspective and differential discounting (4% for costs, 1.5% for effects). Inputs are obtained from the literature and Dutch price lists. Univariate and probabilistic sensitivity analysis are performed., Results: Dapagliflozin is dominant compared with DPP-4 inhibitors, resulting in a €990 cost saving and a 0.28 quality-adjusted life year gain over 40 years. Cost savings are associated mainly with treatment costs and a reduced incidence of micro- and macrovascular complications, among others nephropathy, myocardial infarction and stroke. Results are robust to changes in input parameters., Conclusions: Dapagliflozin is a cost-saving alternative to DPP-4 inhibitors when added to metformin and sulfonylurea. The incidence of micro- and macrovascular complications is lower for people treated with dapagliflozin. Uncertainty around this outcome is low., (© 2020 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aim: To estimate the cost-effectiveness of dapagliflozin added to standard therapy, vs. standard therapy only, in patients with heart failure (HF) with reduced ejection fraction (HFrEF), from the perspective of UK, German, and Spanish payers., Methods and Results: A lifetime Markov model was built to estimate outcomes in patients with HFrEF. Health states were defined by Kansas City Cardiomyopathy Questionnaire total symptom score, type 2 diabetes and worsening HF events. The incidence of worsening HF and all-cause mortality was estimated using negative binomial regression models and parametric survival analysis, respectively. Direct healthcare costs (2019 British pounds/Euro) and patient-reported outcomes (EQ-5D) were sourced from the existing literature and the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF), respectively; the median duration of follow-up in DAPA-HF was 18.2 months (range: 0-27.8). Future costs and effects were discounted at 3.0% for the Spanish and German analyses and 3.5% for the UK analysis. In the UK setting, treatment with dapagliflozin was estimated to increase life-years and quality-adjusted life-years (QALYs) from 5.62 to 6.20 (+0.58) and 4.13 to 4.61 (+0.48), respectively, and reduce lifetime hospitalizations for HF (925 and 820 events per 1000 patients for placebo and dapagliflozin, respectively). Similar results were obtained for Germany and Spain. The incremental cost-effectiveness ratios were £5822, €5379 and €9406/QALY in the UK, Germany and Spain, respectively. In probabilistic sensitivity analyses, more than 90% of simulations were cost-effective at a willingness-to-pay threshold of £20 000/QALY in UK and €20 000/QALY in Germany and Spain., Conclusion: Dapagliflozin is likely to be a cost-effective treatment for HFrEF in the UK, German and Spanish healthcare systems., (© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: Type 2 diabetes mellitus (T2DM) is a major health problem in Egypt with a high impact on morbidity, mortality, and healthcare resources. This study evaluated the budget impact and the long-term consequences of dapagliflozin versus other conventional medications, as monotherapy, from both the societal and health insurance perspectives in Egypt. Methods: A static budget impact model was developed to estimate the financial consequences of adopting dapagliflozin on the healthcare payer budget. We measured the direct medical costs of dapagliflozin (new scenario) as monotherapy, compared to metformin, insulin, sulphonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinedione, and repaglinide (old scenarios) over a time horizon of 3 years. Myocardial infarction (MI), ischemic stroke, hospitalization for heart failure (HHF), and initiation of renal replacement therapy (RRT) rates were captured from DECLARE TIMI 58 trial. One-way sensitivity analyses were conducted. Results: The budget impact model estimated 2,053,908 patients eligible for treatment with dapagliflozin from a societal perspective and 1,207,698 patients from the health insurance (HI) perspective. The new scenario allows for an initial savings of EGP121 million in the first year, which increased to EGP243 and EGP365 million in the second and third years, respectively. The total cumulative savings from a societal perspective were estimated at EGP731 million. Dapagliflozin allows for savings of EGP71, EGP143, and EGP215 million in the first, second and third years respectively, from the HI perspective, with total cumulative savings of EGP430 million over the 3 years. Conclusion: Treating T2DM patients using dapagliflozin instead of conventional medications, maximizes patients' benefits and decreases total costs due to drug cost offsets from fewer cardiovascular and renal events. The adoption of dapagliflozin is a budget-saving treatment option, resulting in substantial population-level health gains due to reduced event rate and cost savings from the perspective of the national healthcare system.

Aim: Cost-effectiveness (CE) analysis of empagliflozin+standard of care (SoC) compared with SoC and liraglutide+SoC, in patients with Type II diabetes and established cardiovascular disease, was conducted using evidence from cardiovascular outcomes trials. Methods: The IQVIA Core Diabetes Model was calibrated to predict same outcomes observed in EMPA-REG OUTCOME and LEADER trials. Three-year observed cardiovascular events of SoC, empagliflozin+SoC and liraglutide+SoC were derived from EMPA-REG OUTCOME trial and an indirect comparison. Time horizon was 50 years and the UK payer perspective was taken. Results: Empagliflozin+SoC dominated liraglutide+SoC with greater quality-adjusted life years and reduced costs. Base-case incremental CE ratio of 6428 GBP/QALY was observed for empagliflozin+SoC versus SoC. Conclusion: Results suggest that empagliflozin+SoC is cost effective versus SoC and liraglutide+SoC.

Background: Dapagliflozin is one of the novel glucose-lowering agents, which has recently been reported to reduce the risk of hospitalization for heart failure (hHF). The present study aimed to compare the differences between the risk of hHF after using dapagliflozin and dipeptidyl peptidase-4 inhibitors (DPP-4i) as second-line drugs for the treatment of type 2 diabetes mellitus using the latest nationwide population data in Korea. Additionally, we aimed to examine the impact of clinical outcomes on direct medical costs in the two groups., Methods: The present population-based, retrospective cohort study was conducted using the nationwide claims data between September 01, 2014 and June 30, 2018. New users of dapagliflozin and DPP-4i were identified from the database and the differences in patients' characteristics between the two groups were analyzed using propensity score-weighted analysis. Cox proportional hazards regression analysis was used to estimate the risk of hHF. A simple model was used for the estimation of direct medical costs for 3 years., Results: In total, 23,147 patients in the dapagliflozin group and 237,187 patients in the DPP-4i group were selected for the analysis. The incidence rates of hHF were 3.86 and 6.79 per 1000 person-years in the dapagliflozin and DPP-4i groups, respectively. In the entire study population, the hazard ratio for hHF in the dapagliflozin group compared to the DPP-4i group was 0.58 (95% confidence interval 0.46-0.74), with 0.55 (95% confidence interval 0.41-0.74) among patients with underlying cardiovascular disease and 0.66 (95% confidence interval 0.46-0.95) among patients without underlying cardiovascular disease. The direct medical costs were $57,787 lower in the dapagliflozin group than in the DPP-4i group for 3 years., Conclusions: This study showed that dapagliflozin lowers the risk for hHF and subsequently reduces direct medical costs compared to DPP-4i. The protective effect against hHF was more evident among patients with underlying cardiovascular disease.

Aims: Controlling costs while maximizing healthcare gains is the predominant challenge for healthcare providers, and therefore cost-effectiveness analysis is playing an ever-increasing role in healthcare decision making. The aim of the present analysis was to assess the long-term cost-effectiveness of subcutaneous once-weekly semaglutide (0.5 mg and 1 mg) versus empagliflozin (10 mg and 25 mg) in the Spanish setting for the treatment of patients with type 2 diabetes (T2D) with inadequate glycemic control on oral anti-hyperglycemic medications. Material and methods: The IQVIA CORE Diabetes Model was used to project outcomes over patient lifetimes with once-weekly semaglutide versus empagliflozin, with treatment effects based on a network meta-analysis. The analysis captured treatment costs, costs of diabetes-related complications, and the impact of complications on quality of life, based on published sources. Outcomes were discounted at 3.0% per annum . Results: Once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in discounted quality-adjusted life expectancy of 0.12 and 0.15 quality-adjusted life years (QALYs), respectively, versus empagliflozin 10 mg and improvements of 0.11 and 0.14 QALYs, respectively, versus empagliflozin 25 mg. Treatment costs were higher with once-weekly semaglutide compared with empagliflozin, but this was partially offset by cost savings due to avoidance of diabetes-related complications. Once-weekly semaglutide 0.5 mg and 1 mg were associated with incremental cost-effectiveness ratios of EUR 2,285 and EUR 161 per QALY gained, respectively, versus empagliflozin 10 mg, and EUR 3,090 and EUR 625 per QALY gained, respectively, versus empagliflozin 25 mg. Conclusions: Based on a willingness-to-pay threshold of EUR 30,000 per QALY gained, once-weekly semaglutide 0.5 mg and 1 mg were projected to be cost-effective versus empagliflozin 10 mg and 25 mg for the treatment of patients with T2D with inadequate glycemic control on oral anti-hyperglycemic medications in the Spanish setting, irrespective of patients' BMI at baseline.

Aims: To investigate how the cardiovascular (CV) risk benefits of dapagliflozin translate into healthcare costs compared with other non-sodium-glucose cotransporter-2 inhibitor glucose-lowering drugs (oGLDs) in a real-world population with type 2 diabetes (T2D) that is similar to the population of the DECLARE-TIMI 58 trial., Methods: Patients initiating dapagliflozin or oGLDs between 2013 and 2016 in Swedish nationwide healthcare registries were included if they fulfilled inclusion and exclusion criteria of the DECLARE-TIMI 58 trial (DECLARE-like population). Propensity scores for the likelihood of dapagliflozin initiation were calculated, followed by 1:3 matching with initiators of oGLDs. Per-patient cumulative costs for hospital healthcare (in- and outpatient) and for drugs were calculated from new initiation until end of follow-up., Results: A total of 24 828 patients initiated a new GLD; 6207 initiated dapagliflozin and 18 621 initiated an oGLD. After matching based on 96 clinical and healthcare cost variables, groups were balanced at baseline. Mean cumulative 30-month healthcare cost per patient was similar in the dapagliflozin and oGLD groups ($11 807 and $11 906, respectively; difference, -$99; 95% CI, -$629, $483; P = 0.644). Initiation of dapagliflozin rather than an oGLD was associated with significantly lower hospital costs (-$658; 95% CI, -$1169, -$108; P = 0.024) and significantly higher drug costs ($559; 95% CI, $471, $648; P < 0.001). Hospital cost difference was related mainly to fewer CV- and T2D-associated complications with use of dapagliflozin compared with use of an oGLD (-$363; 95% CI, -$665, -$61; P = 0.008)., Conclusion: In a nationwide, real-world, DECLARE-like population, dapagliflozin was associated with lower hospital costs compared with an oGLD, mainly as a result of reduced rates of CV- and T2D-associated complications., (© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Introduction: Oral semaglutide is the first orally administered glucagon-like peptide-1 receptor agonist for the treatment of type 2 diabetes, and has been evaluated in the PIONEER clinical trial program. These trials assessed the proportions of patients achieving single and composite endpoints, encompassing glycemic control [defined in terms of glycated hemoglobin (HbA1c)], weight loss, and hypoglycemia. The present study assessed the cost of control with oral semaglutide versus empagliflozin, sitagliptin, and liraglutide in the US., Methods: Four endpoints were evaluated: (1) HbA1c ≤ 6.5%; (2) HbA1c < 7.0%; (3) ≥ 1.0%-point HbA1c reduction and weight loss ≥ 3.0%; and (4) HbA1c < 7.0% without hypoglycemia and without weight gain. The proportions of patients achieving each endpoint were sourced from the PIONEER 2, 3 and 4 trials. Treatment costs were accounted over an annual time-period in 2019 US dollars (USD), based on wholesale acquisition cost. Cost of control was calculated by dividing treatment costs by the proportion of patients achieving each target., Results: Oral semaglutide was consistently associated with the lowest cost of control for all four endpoints. For the targets of HbA1c ≤ 6.5% and HbA1c < 7.0%, oral semaglutide 14 mg was associated with lower cost of control than empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg by USD 15,036, 14,697, and 6996, respectively, and USD 931, 346 and 4497, respectively. For the double composite endpoint, cost of control was lower with oral semaglutide 14 mg by USD 525, 32,277 and 13,011, respectively versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg. For the triple composite endpoint, cost of control was lower with oral semaglutide 14 mg by USD 1255, 7510 and 5774, respectively., Conclusion: Oral semaglutide was associated with lower cost of bringing patients with type 2 diabetes to four clinically-relevant treatment targets versus empagliflozin, sitagliptin, and liraglutide in the US., Funding: Novo Nordisk A/S.

Aim: In the EMPA-REG OUTCOME trial, empagliflozin therapy reduced cardiovascular death by 38% compared with placebo when added to standard of care. Using the trial results, we created a discrete-event simulation model to assess lifetime health economic outcomes in people with Type 2 diabetes and established cardiovascular disease., Methods: Time-dependent survival regression analysis was performed on data from EMPA-REG OUTCOME for 10 cardiovascular and renal events (e.g. stroke, heart failure hospitalization, macroalbuminuria, cardiovascular mortality) to capture event rates over time, and interaction between events. Model performance was assessed by comparing predicted and observed outcomes at 3 years. Costs in the United Kingdom (UK) and health utilities were obtained from published literature. Outcomes included cumulative event rates, life-years, costs and quality-adjusted life-years (QALYs)., Results: The model predicted an 18% relative increase (by 2.1 life-years) in survival for empagliflozin (14.0 life-years) vs. standard of care (11.9 life-years), attributable to direct treatment effect on cardiovascular mortality, and to indirect effect via reductions in other events. Participants treated with empagliflozin may experience improved quality of life (1.0 QALY) and higher costs (£3737/participant), yielding an incremental cost-effectiveness ratio (ICER) of £4083/QALY. Sensitivity analyses confirmed the robustness of these results to changes in input parameters., Conclusions: Based on extrapolation of EMPA-REG OUTCOME trial data using a participant-level simulation model, empagliflozin in addition to standard of care is projected to be highly cost-effective using UK healthcare costs. The impact in other countries will vary due to differences in drug pricing and accrual of other costs. (Clinical Trial Registry No: NCT01131676)., (© 2019 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Purpose: The goal of this study was to assess the cost-effectiveness of empagliflozin in Japan based on the Asian subpopulation in the EMPA-REG OUTCOME trial., Methods: The trial has shown a reduction in the risk for cardiovascular (CV) and renal events with empagliflozin in patients with type 2 diabetes mellitus and established CV disease. A cost-effectiveness analysis based on the overall population of the EMPA-REG OUTCOME trial was reported previously by using a lifetime discrete event simulation model. The same modeling frame was adapted to evaluate the cost-effectiveness of treatment with empagliflozin added to standard of care (SoC) compared with SoC alone in Japan. The time to relevant clinical events and the hazard ratios were derived from an Asian subpopulation in the EMPA-REG OUTCOME trial. The costs for each event were estimated from a Japanese medical claims database. Direct medical costs, life expectancy, and quality-adjusted life years (QALYs) were calculated from the public health care perspective., Findings: Treatment with empagliflozin was estimated to increase life expectancy by 6.2 years and 2.7 QALYs, whereas total cost increased by 1,115,475 yen compared with treatment with SoC alone. The incremental cost-effectiveness ratio was 415,849 yen/QALY. In the sensitivity analysis, there was no case that was in excess of the reference value of the incremental cost-effectiveness ratio in the pilot introduction for price revision in Japan (ie, 5 million yen/QALY)., Implications: Based on the Asian subpopulation in the EMPA-REG OUTCOME trial, our results suggest that empagliflozin added to SoC is highly cost-effective compared with SoC alone in Japan., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Dapagliflozin is the first SGLT2 inhibitor available in China, where the disease burden of diabetes and its complications is very heavy. Because a new diabetes treatment strategy for diabetes should consider its cost-effectiveness, compared with an existing treatment, this study aimed to examine the cost-effectiveness between dapagliflozin and metformin treatment in China., Methods: The Cardiff Diabetes Model (CDM) was used to estimate cost effectiveness and macro- and micro-vascular outcomes of dapagliflozin vs metformin. The CDM effectiveness inputs were derived from indirect comparative efficacy data from meta-analysis of 71 studies comparing monotherapy and add-on therapy of dapagliflozin vs metformin: dapagliflozin or metformin monotherapy, add-on therapy with other oral hypoglycemic agents, and add-on therapy with insulin. Direct medication costs and medical costs on treating diabetes were calculated based on published and local sources. A discount rate of 3% was applied to both costs and health effects. Univariate and probabilistic sensitivity analyses (PSA) were performed to assess uncertainties., Results: The total healthcare costs accumulated over the lifetime on dapagliflozin treatment arm was 8,626 Chinese yuan higher than the metformin treatment arm for an individual patient, and the quality adjusted life years (QALYs) gained with dapagliflozin treatment was 0.8 more than metformin treatment. Therefore, an incremental cost-effectiveness ratio was 10,729 yuan per QALY gained for dapagliflozin treatment arm vs metformin treatment arm. The cost-effectiveness results were robust to various sensitivity analyses., Conclusion: Dapagliflozin treatment was more cost-effective compared with metformin treatment for Chinese type 2 diabetes patients. However, the findings of favorable cost-effectiveness results for dapagliflozin are largely driven by the effects of favorable weight profile on clinical, utility, and costs in the Cardiff model.

The present study sought to evaluate the cost-effectiveness of first-line (immediate) versus delayed use of combination dapagliflozin and metformin in patients with type 2 diabetes, from the perspective of the Australian healthcare system. We developed a Markov model to simulate the progress of subjects with type 2 diabetes. Decision analysis was applied to assess the cost-effectiveness of first-line combination dapagliflozin and metformin versus first-line metformin monotherapy followed by gradual addition of dapagliflozin over time. Transition probabilities, costs (in Australian dollars) and utility data were derived from published sources. All costs, years of life lived and quality adjusted life years (QALYs) lived were discounted at an annual rate of 5%. Over a 20-year model period, first-line use of combination dapagliflozin and metformin was predicted to reduce the onset of hospitalisation of heart failure, cardiovascular deaths and all cause deaths by 5.5%, 57.6% and 29.6%, respectively. An additional 2.5 years of life (discounted) and 1.9 QALYs (discounted) would be gained per patient, at a cost of AUD $23,367 (discounted) per person. These figures equated to AUD $9,535 per years of life saved (YoLS) and AUD $12,477 per QALYs saved. Sensitivity analyses indicated the results to be robust. Compared to first-line metformin monotherapy followed by gradual addition of dapagliflozin, first-line use of combination dapagliflozin and metformin is likely to be a cost-effective approach to the management of Australians with type 2 diabetes mellitus.

Aims: To compare healthcare costs and utilization in patients with type 2 diabetes (T2D) who initiated dapagliflozin (DAPA) with costs and utilization in those who initiated sitagliptin (SITA) in a real-world setting., Materials and Methods: This was a retrospective study of health plan enrollees in two US commercial claims databases or Medicare Part D. The study population comprised adult patients with T2D who initiated DAPA or SITA between January 1, 2014 and April 30, 2015. DAPA and SITA initiators were propensity-score-matched, and healthcare utilization and costs during the 1-year follow-up period were compared. Analyses were conducted separately for patients with evidence of oral antidiabetic drug (OAD) monotherapy use at baseline., Results: A total of 2722 patients were included in each matched cohort. Follow-up unadjusted all-cause costs ($16 065 and $17 281; P = 0.135) and diabetes-related costs ($9697 and $9354; P = 0.539) were similar in the DAPA and SITA cohorts. Higher office and outpatient visit costs in the SITA group were offset by higher pharmacy costs in the DAPA group. In the subgroup of 1804 patients with OAD monotherapy use at baseline, patients in the SITA group had higher total all-cause costs compared with those in the DAPA group ($14 884 vs. $12 353; P = 0.026)., Conclusion: Patients who initiated DAPA or SITA had similar all-cause and diabetes-related healthcare costs over 1 year of follow-up. In the subgroup of patients treated with OAD monotherapy at baseline (84% metformin monotherapy), those who initiated DAPA as add-on therapy had lower costs than patients who added SITA., (© 2018 John Wiley & Sons Ltd.)

Empagliflozin, an inhibitor of sodium-glucose cotransporter 2 and Liraglutide, a glucagon-like peptide 1 analogue, were both proved to significantly reduce the incidence of cardiovascular (CV) death in patients with type 2 diabetes and established CV disease. However, addition of either drug to current diabetes treatment regimens may impose a significant burden on healthcare systems. We performed a cost-minimization analysis of Empagliflozin versus Liraglutide for preventing CV death. Rates of prevention of CV death were extracted from the published data of the EMPA-REG OUTCOME and LEADER trials. Drug costs were extracted from the US National Average Drug Acquisition Costs of 2017. In the EMPA-REG OUTCOME trial 5,833 patient-years of treatment with Empagliflozin resulted in the prevention of 51 CV deaths. In LEADER, 16,338 patient-years of Liraglutide resulted in the prevention of 59 CV deaths. The price in 2017 of annual Empagliflozin and Liraglutide therapy was $4,980 and $9,300, respectively. Therefore, the cost of Empagliflozin or Liraglutide needed to prevent 1 CV death would be $569,526 (95% confidence interval $415,713 to $921,798) and $2,575,312 (95% confidence interval $1,607,526 to $7,807,986), respectively. In conclusion, use of Empagliflozin for preventing CV death in type 2 diabetes patients with an established CV disease seems to be a major cost-saving strategy compared with Liraglutide. These results should be considered in the context of other individual drug and patient factors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

BACKGROUND Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by repeated episodes of reduction in airflow due to the collapse of the upper airway during sleep. The aim of this study was to compare clinical outcome, side effects, and cost of treatment between modafinil and intranasal mometasone furoate in patients with OSAHS. MATERIAL AND METHODS Patients with OSAHS (N=250) were divided into two groups: the modafinil group (MG) (N=125) were treated with 100 mg modafinil twice a day; the intranasal mometasone furoate group (IMFG) (N=125) were treated with 100 µg of intranasal mometasone furoate in the evening. Quality of life, grading of OSAHS, plain-film radiography, the adenoidal-nasopharyngeal ratio (AN ratio), side effects, cost of treatment, and beneficial effects after discontinuation of treatment were evaluated for all patients. RESULTS Duration of sleep apnea was significantly reduced in the IMFG compared with the MG (p=0.0145, q=9.262). Modafinil and intranasal mometasone furoate both had moderate effects on improvement of the OSAHS score. The IMFG showed a significantly greater beneficial effect on the AN ratio when compared with the MG (p=0.0001, q=6.584). No adverse events of treatment with modafinil and intranasal mometasone furoate were reported. Cost of treatment and beneficial effect after discontinuation were both significantly greater for the IMFG compared with the MG. CONCLUSIONS The findings of this preliminary clinical study were that for patients diagnosed with OSAHS, night-time treatment with intranasal mometasone furoate was more effective than modafinil.

Background and Objective: Type 2 diabetes mellitus (T2DM) is frequently associated with co-morbidities that exacerbate cardiovascular (CV) risk. CV disease is the leading cause of death in people with diabetes across the world and accounts for approximately half the deaths in the T2DM population. Hence, the objective of present study was to evaluate the cost-effectiveness of empagliflozin, in addition to standard of care (SoC), for the treatment of adult patients with T2DM and high CV risk in Greece., Methods: A health economic model was used to project clinical and economic outcomes of patients receiving empagliflozin plus SoC compared with those receiving SoC alone over a lifetime horizon. CV and renal event rates were derived from patient level data from the EMPA-REG-OUTCOME ® trial by fitting time-dependent parametric survival functions. 5000 individual patient profiles randomly sampled from the trial were simulated using a time-to-event approach. Model extrapolated outcomes included life years (LYs), quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Following a Greek third-party payer perspective, only direct medical costs related to drug acquisition as well as fatal and non-fatal diabetes-related complications were considered (€2016). Cost units and utility data were extracted from the literature and publicly available official sources. Sensitivity analyses explored the impact of changes in input data., Results: Over a patient's lifetime, empagliflozin was predicted to result in longer mean survival (14.01 LY vs. 11.87 LY with SoC) and reduced rate of clinical events accumulating 7.75 QALYs versus 6.83 QALYs on SoC alone at additional costs of €4235. The generated ICER of empagliflozin was €4633 per QALY gained. One-way sensitivity analysis confirmed empagliflozin's cost-effective profile. At the defined willingness-to-pay threshold of €34,000 per QALY gained, probabilistic sensitivity analysis showed that empagliflozin was estimated to have a 100% probability of being cost-effective relative to SoC., Conclusions: Empagliflozin added to SoC was estimated to be a highly cost-effective treatment option for the treatment of T2DM in adults with increased CV disease risk in Greece.

Aims: In the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG) trial, empagliflozin reduced cardiovascular and all-cause mortality in type 2 diabetes (T2D) patients at high cardiovascular risk. We sought to estimate the cost-effectiveness of empagliflozin versus standard treatment for the prevention of cardiovascular morbidity and mortality in patients with T2D., Methods: A Markov model was developed to assess the cost-effectiveness of empagliflozin (versus standard treatment) for the prevention of cardiovascular morbidity and mortality in patients with T2D using a 3-month cycle length and a lifetime horizon. Data sources included the EMPA-REG randomized clinical trial and other published epidemiological studies. Outcomes included treatment costs (in 2016 US$), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Probabilistic sensitivity analysis (PSA) was performed to test the robustness of conclusions., Results: Empagliflozin use resulted in higher total lifetime treatment costs ($371,450 versus $272,966) but yielded greater QALYs (10.712 vs. 9.419) compared to standard treatment. This corresponded to an ICER of $76,167 per QALY gained. PSA suggested empagliflozin would be cost-effective in 96% of 10,000 iterations assuming a willingness-to-pay threshold of $100,000 per QALY gained., Conclusion: Empagliflozin may be cost-effective compared to standard treatment in T2D patients at high cardiovascular risk., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Bisphenol A (BPA), a widely used petrochemical compound, has become an emerging global environmental management challenge because its leakage is associated with potential environmental and human health impacts. Until now, available BPA statistics have been limited to the products that directly use BPA. In this study, we delineate direct and indirect BPA flows for the 2012 Chinese economy. We find that construction, production of educational and recreational products, and automobile manufacturing are the most BPA-intensive sectors in terms of total BPA flows (300, 157, and 130 Gg total BPA flows, respectively). The public management and health sectors, however, incur significant indirect BPA flows, defined as embedded and inter-sectoral BPA placed into use, even though direct BPA use by these sectors is limited. By revealing the currently overlooked indirect BPA flows, this study reveals data gaps that are highly relevant to improving the accuracy of estimated BPA flows and losses. The method used herein is transferrable to other emerging and environmentally relevant materials, thereby providing the holistic understanding needed for cities, regions, or nations to design effective policy interventions.

Objective: This study evaluates the cost of achieving glycemic control with three sodium glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin, dapagliflozin, and empagliflozin, in patients with type 2 diabetes mellitus (T2DM) from the payer perspective in the United Arab Emirates (UAE)., Methods: A systematic literature review identified randomized controlled trials of antihyperglycemic agents as add-on to metformin in patients with T2DM of 26 ± 4 weeks in duration, published by 10 September 2014. A Bayesian network-meta analysis (NMA) compared HbA1c changes with canagliflozin 100 and 300 mg versus dapagliflozin 10 mg and empagliflozin 10 and 25 mg. The cost associated with a 1% placebo-adjusted HbA1c reduction with each SGLT2 inhibitor as add-on to metformin was calculated based on NMA results and UAE drug costs., Results: In the NMA, canagliflozin 100 and 300 mg were associated with HbA1c reductions (-0.67% and -0.79%) compared with dapagliflozin 10 mg (-0.41%) and empagliflozin 10 and 25 mg (-0.57% and -0.64%). Probabilities of canagliflozin 100 mg performing better were 79%, 60%, and 53% versus dapagliflozin 10 mg and empagliflozin 10 and 25 mg, respectively; probabilities for canagliflozin 300 mg performing better were 88%, 72%, and 65%, respectively. The cost per 1%-point reduction in HbA1c was projected to be lower with canagliflozin 100 and 300 mg ($448 and $422) compared with dapagliflozin 10 mg ($785) and empagliflozin 10 and 25 mg ($527 and $563)., Conclusions: Canagliflozin may provide a greater glycemic response at a lower effective cost than dapagliflozin or empagliflozin for patients with T2DM inadequately controlled with metformin from the payer perspective in the UAE.

Objective: To evaluate the long-term cost-effectiveness of dapagliflozin (a novel sodium-glucose co-transporter-2 inhibitor) versus glimepiride (a widely used sulfonylurea), when applied as monotherapy in patients with type 2 diabetes mellitus (T2DM) in China., Methods: Literature screening, meta-analysis and indirect comparison were used to compare efficacy and safety between dapagliflozin and glimepiride. Direct medication costs and medical expenditure on treating diabetes related comorbidities were calculated based on published and local sources and reported in 2015 Chinese Renminbi (RMB). A discount rate of 3% was applied to both costs and health effects. The Cardiff model, an economic model designed to evaluate the cost-effectiveness of comparator therapies in diabetes, was used to generate outputs including macrovascular and microvascular complications, diabetes-specific mortality, costs and quality-adjusted life years (QALYs) over a time horizon of 40 years from the health provider perspective. Univariate and probabilistic sensitivity analyses were performed to assess uncertainty in the model results., Results: Compared with glimepiride, patients on dapagliflozin gained 1.01 QALYs, at a cost saving of RMB 49,065 in our simulated cohort. This resulted in a cost saving of RMB 48,585 per QALY gained with dapagliflozin. The cost-effectiveness results were robust to various sensitivity analyses including probabilistic sensitivity analysis (PSA)., Conclusions: Compared with glimepiride, dapagliflozin as monotherapy for T2DM is a more cost-effective treatment for T2DM patients on monotherapy in China. The weight control has been identified as the major contributor for the higher cost-effectiveness of dapagliflozin.

Background: Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors., Objective: To review the clinical effectiveness and cost-effectiveness of dapagliflozin (Farxiga, Bristol-Myers Squibb, Luton, UK), canagliflozin (Invokana, Janssen, High Wycombe, UK) and empagliflozin (Jardiance, Merck & Co., Darmstadt, Germany), in monotherapy in people who cannot take metformin., Sources: MEDLINE (1946 to February 2015) and EMBASE (1974 to February 2015) for randomised controlled trials lasting 24 weeks or more. For adverse events, a wider range of studies was used. Three manufacturers provided submissions., Methods: Systematic review and economic evaluation. A network meta-analysis was carried out involving the three SGLT2 inhibitors and key comparators. Critical appraisal of submissions from three manufacturers., Results: We included three trials of dapagliflozin and two each for canagliflozin and empagliflozin. The trials were of good quality. The canagliflozin and dapagliflozin trials compared them with placebo, but the two empagliflozin trials included active comparators. All three drugs were shown to be effective in improving glycaemic control, promoting weight loss and lowering blood pressure (BP)., Limitations: There were no head-to-head trials of the different flozins, and no long-term data on cardiovascular outcomes in this group of patients. Most trials were against placebo. The trials were done in patient groups that were not always comparable, for example in baseline glycated haemoglobin or body mass index. Data on elderly patients were lacking., Conclusions: Dapagliflozin, canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Boehringer Ingelheim, Bracknell, UK)., Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: The impact of formulary management strategies on utilization and expenditures in overactive bladder (OAB) treatment has not been extensively investigated. In 2013, step therapy (ST) policies for 2 branded OAB treatments, mirabegron and fesoterodine, were removed from Humana Medicare Advantage Prescription Drug (MAPD) plans and Medicare prescription drug plans (PDP), allowing for an examination of the effect of ST policies on OAB medication use patterns and costs., Objective: To assess the impact of removal of formulary restriction policies for mirabegron and fesoterodine on medication utilization patterns and costs associated with OAB treatment in Medicare patients., Methods: A retrospective cross-sectional study design was utilized. Subjects included individuals enrolled in Humana MAPD plans or PDPs, aged ≥ 65 years, with ≥ 1 prescription for an OAB medication in 2013. Patient demographic characteristics, OAB medication utilization, and pharmacy cost trends in 2013 were described. OAB medication use was calculated as the number of 30-day-supply equivalent medication claims and reported as a percentage of the total number of 30-day-supply equivalent claims across all OAB products. OAB medication expenditures were calculated as a percentage of the sum of pharmacy costs for OAB medications and reported separately for each month and drug during 2013. Temporal trends of OAB medication utilization and expenditures in 2013 were calculated using ordinary least squares regression., Results: Of 194,511 patients, trends in utilization of OAB medications indicated that on average, there was a statistically significant monthly increase in utilization of mirabegron (regression coefficient [B] = 274; P < 0.001; 95% CI: 218, 330), fesoterodine (B = 167; P < 0.001; 95% CI = 129, 205), oxybutynin extended release (ER; B = 357; P = 0.011; 95% CI = 99, 614), and trospium ER (B = 33; P = 0.001; 95% CI = 17, 50) and statistically significant decreases in utilization of solifenacin (B = -202; P = 0.048; 95% CI = -402, -2), tolterodine ER (B = -287; P = 0.002; 95% CI = -437, -137), darifenacin (B = -94; P < 0.001; 95% CI = -128, -61), and trospium immediate release (IR; B = -22; P = 0.001; 95% CI = -32, -12). Total OAB medication expenditures significantly increased an average of 0.12% for each month during the course of 2013 (B = 0.12; P = 0.026; 95% CI = 0.017, -0.223). While monthly oxybutynin IR utilization did not change significantly throughout 2013 (B = 228; P = 0.169; 95% CI = -114, -570), it demonstrated the largest average monthly expenditure increase (B = 0.082; P < 0.001; 95% CI = 0.056, 0.108). When removing oxybutynin IR costs from the total OAB medication costs, the trend in total OAB medication average monthly expenditures was not significant (B = 0.038; P = 0.365; 95% CI = -0.051, -0.126). An over 4-fold per-unit-cost increase for oxybutynin IR was noted., Conclusions: Utilization of 2 branded OAB products increased in the months after ST removal with minimal cost impact. One of the possible reasons total OAB expenditures increased may have been due to the increased cost of the largest-volume generic product, oxybutynin IR., Disclosures: This research was funded by Astellas Pharma Global Development and was conducted as part of the Astellas-Humana Research Collaboration. Ng, Kristy, Schermer, and Bradt are employees of Astellas. Astellas manufactures mirabegron (Myrbetriq) and solifenacin (VESIcare). Abbass, Caplan, Collins, and Suehs are employees of Comprehensive Health Insights, a subsidiary of Humana, which received funding from Astellas for this study. Suehs owns stock in Humana. Chan is an employee of Humana Pharmacy Solutions. Portions of this study were presented as a poster at Academy of Managed Care Pharmacy Nexus 2015; October 26-29, 2015; Orlando, Florida. Study concept and design were contributed by Ng, Chan, Suehs, and Abbass, along with Collins. Abbass took the lead in data collection, along with Collins and with assistance from Caplan, Chan, and Suehs. Data interpretation was provided by Kristy and Bradt, along with Abbass, Caplan, Ng, Suehs, Collins, and Chan. The manuscript was written primarily by Caplan, along with Schermer, Suehs, and Abbass, and revised by Caplan, Schermer, and Ng, along with the other authors.

Objective: To estimate the long-term cost-effectiveness of dapagliflozin versus acarbose as monotherapy in treatment-naïve patients with type 2 diabetes mellitus (T2DM) in China., Methods: The Cardiff Diabetes Model, an economic model designed to evaluate the cost-effectiveness of comparator therapies in diabetes was used to simulate disease progression and estimate the long-term effect of treatments on patients. Systematic literature reviews, hospital surveys, meta-analysis and indirect treatment comparison were conducted to obtain model-required patient profiles, clinical data and costs. Health insurance costs (2015¥) were estimated over 40 years from a healthcare payer perspective. Univariate and probabilistic sensitivity analyses were performed., Results: The model predicted that dapagliflozin had lower incidences of cardiovascular events, hypoglycemia and mortality events, was associated with a mean incremental benefit of 0.25 quality-adjusted life-years (QALYs) and with a lower cost of ¥8,439 compared with acarbose. This resulted in a cost saving of ¥33,786 per QALY gained with dapagliflozin. Sensitivity analyses determined that the results are robust., Conclusion: Dapagliflozin is dominant compared with acarbose as monotherapy for Chinese T2DM patients, with a little QALY gain and lower costs. Dapagliflozin offers a well-tolerated and cost-effective alternative medication for treatment-naive patients in China, and may have a direct impact in reducing the disease burden of T2DM., Competing Interests: This study was funded by AstraZeneca. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: To evaluate the cost-effectiveness of first-line treatment of Overactive Bladder (OAB) with fesoterodine relative to mirabegron, from the Spanish National Health System (NHS) perspective., Methods: A decision tree model was developed to represent a typical clinical process of 52-week of treatment for an OAB patient with urge urinary incontinence (UUI) initiating first-line therapy with fesoterodine 4mg, including optional titration to 8mg, vs.mirabegron 50mg. Efficacy data were obtained from a Bayesian indirect treatment meta-analysis. Patients with UUI of less than one episode/day were defined as treatment responder and persistence was assessed at weeks 4, 12 and 24. At week 12, non-responders discontinued treatment permanently. Quality-adjusted life years (QALYs) were calculated based on time spent in responder and non-responder states. OAB-related drug and medical care costs including physician visits, laboratory tests, incontinence pads, and comorbidities (fracture, skin infection, urinary tract infections and depression) were modeled and expressed in €2015., Results: At week 52, the percentage of responders was 20.8% for patients starting on fesoterodine 4mg who optionally titrated to 8mg and 19.4% for patients treated with mirabegron. QALYs were slightly higher with fesoterodine than mirabegron (0.7703vs. 0.7668, difference=0.0035). Fesoterodine treatment also had slightly higher total costs than mirabegron (3,296€vs. 3,217, difference=79€), resulting in a cost of 22,523/QALY€ gained for fesoterodine versus mirabegron. Probabilistic sensitivity analysis confirmed the slight advantage of fesoterodine with a 61.1% probability of being cost-effective at the 30,000€ willingness-to-pay for 1QALY threshold., Conclusions: Given the relatively small 1-year cost difference between the two treatments, fesoterodine can be considered a cost-effective option relative to mirabegron for the first-line management of OAB with UUI in Spain., (Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Objective: Type 2 diabetes mellitus (T2DM) is a chronic progressive disease that has been spread worldwide over the past three decades and associated with increased morbidity and mortality resulting in considerable socioeconomic implications for national healthcare systems. Effective management of disease is highly needed ensuring patients receive the best possible care within the available budget. The objective of this study was to evaluate the long-term cost-effectiveness of dapagliflozin, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, compared with a sulfonylurea (SU) or a dipeptidyl-peptidase-4 inhibitor (DPP-4i), when added to metformin, in T2DM patients inadequately controlled on metformin alone in Greece., Methods: The published and validated Cardiff diabetes model, a lifetime micro-simulation model, was adapted to a Greek healthcare setting to determine the incidence of micro- and macro-vascular complications and diabetes-specific and all-cause mortality. Clinical, cost, and utility data were retrieved from literature and assigned to model parameters to calculate total quality-adjusted life-years (QALYs) and total costs as well as incremental cost-effectiveness ratios (ICERs). The analysis was conducted from the perspective of a third-party payer in Greece. Uncertainty surrounding important model parameters was explored with univariate and probabilistic sensitivity analyses (PSA)., Results: Over a patient's lifetime, dapagliflozin was associated with 0.48 and 0.04 incremental QALYs compared with SU and DPP-4i, respectively, at additional costs of €5142 and €756, respectively. The corresponding ICERs were €10,623 and €17,695 per QALY gained versus the treatment with SU and DPP-4i, respectively. Results were robust across various univariate and scenario analyses. At the defined willingness-to-pay threshold of €34,000 per QALY gained, PSA estimated that treatment with dapagliflozin had a 100 % and 79.7 % probability of being cost-effective relative to the SU and DPP-4i treatments., Conclusions: Dapagliflozin in combination with metformin was shown to be a cost-effective treatment alternative for patients with T2DM whose metformin regimen does not provide sufficient glycemic control in a Greek healthcare setting.

Objectives: To assess the costs of treating overactive bladder (OAB) with fesoterodine compared to no OAB pharmacotherapy among vulnerable elderly from the US payer perspective., Methods: A decision analytic cost model was developed to estimate the 52-week costs of a cohort of vulnerable elderly with OAB initiating treatment with fesoterodine or no OAB pharmacotherapy. Vulnerable elderly OAB patients were defined as those aged ≥65 years with self-reported urge urinary incontinence (UUI) symptoms for ≥3 months, 2-15 UUI episodes/day, and at risk of deteriorating health by a score of ≥3 on the Vulnerable Elders Survey (VES)-13. Patients were evaluated for fesoterodine treatment response (defined as no UUI episodes) and persistence at weeks 12, 26, and 52. The model included a hypothetical health plan with 100,000 elderly members. A total of 7096 vulnerable elderly subjects were identified as the model target population based on the percentage of vulnerable elderly and annual prevalence of OAB among vulnerable elderly. OAB-related costs included fesoterodine drug acquisition costs, healthcare resource use (inpatient hospitalization, outpatient visits, and physician office visits), and OAB-related co-morbidities (falls/fractures, urinary tract infections, depression, and nursing home admissions). All costs were inflated to 2013 US$ using the medical care component of the consumer price index (CPI)., Results: When 7096 vulnerable elderly OAB patients were treated with fesoterodine, US healthcare payers could save $11,463,981 per year, or $1616 per patient vs no OAB pharmacotherapy. Univariate one-way sensitivity analyses supported the robustness of the findings and showed results were most sensitive to changes in fesoterodine efficacy followed by annual costs of inpatient hospitalization., Conclusions: From a US payer perspective, treating vulnerable elderly OAB patients with fesoterodine was cost-saving compared to no OAB pharmacotherapy.

Background: Overactive bladder (OAB) is a syndrome characterized by presenting symptoms of urgency, with or without urge incontinence, and normally accompanied by day and night frequency., Objective: The aim of this study was to evaluate the impact of lost work productivity [number of days of sick leave] in patients treated with fesoterodine versus tolterodine and solifenacin to treat OAB in Spain., Methods: A retrospective, observational study was carried out using the records (digital databases) of actively working patients (2008-2013). The study population comprised of patients from two autonomous communities; 31 primary care centres agreed to participate. Patients who began first treatment with antimuscarinics (fesoterodine, solifenacin or tolterodine) and who met certain inclusion/exclusion criteria were included in the study. Follow-up lasted for 1 year. The main outcome measures were comorbidity, medication possession ratio (MPR), treatment persistence, and number of days of sick leave and associated costs. Indirect costs were considered to be those related to lost work productivity (number of days of sick leave, exclusively), (1) due to OAB and (2) overall total. The cost was expressed as the average cost per patient (cost/unit). Multivariate analyses (Cox, ANCOVA) were used to correct the models., Results: A total of 3094 patients were recruited into the study; 43.0 % were treated with solifenacin, 29.2 % with tolterodine, and 27.8 % with fesoterodine. The average age of patients was 54 years (standard deviation 9.2), and 62.2 % were women. The comparison of fesoterodine versus solifenacin and tolterodine showed a higher MPR (90.0 vs. 87.0 and 86.1 %, respectively), higher treatment persistence (40.2 vs. 34.7 and 33.6 %), lower use of sick leave (22.8 vs. 52.9 and 36.7 %), total number of days of sick leave (5.1 vs. 9.7 and 9.3 days) and costs corrected for covariates (€371 vs. €703 and €683); p < 0.05., Conclusions: Despite the possible limitations of this study, active patients who began treatment with fesoterodine to treat OAB (compared with solifenacin or tolterodine) had fewer days of sick leave, resulting in lower costs due to lost productivity.

Background: Type 2 diabetes mellitus (T2DM) is a chronic, progressive condition where the primary treatment goal is to maintain control of glycated haemoglobin (HbA1c). In order for healthcare decision makers to ensure patients receive the highest standard of care within the available budget, the clinical benefits of each treatment option must be balanced against the economic consequences. The aim of this study was to assess the cost-effectiveness of dapagliflozin, the first-in-class sodium-glucose co-transporter 2 (SGLT2) inhibitor, compared with a dipeptidyl peptidase-4 inhibitor (DPP-4i), when added to metformin for the treatment of patients with T2DM inadequately controlled on metformin alone., Methods: The previously published and validated Cardiff diabetes model was used as the basis for this economic evaluation, with treatment effect parameters sourced from a systematic review and network meta-analysis. Costs, derived from a UK healthcare system perspective, and quality-adjusted life years (QALYs), were used to present the final outcome as an incremental cost-effectiveness ratio (ICER) over a lifetime horizon. Univariate and probabilistic sensitivity analyses (PSA) were carried out to assess uncertainty in the model results., Results: Compared with DPP-4i, dapagliflozin was associated with a mean incremental benefit of 0.032 QALYs (95% confidence interval [CI]: -0.022, 0.140) and with an incremental cost of £216 (95% CI: £-258, £795). This resulted in an ICER point estimate of £6,761 per QALY gained. Sensitivity analysis determined incremental costs to be insensitive to variation in most parameters, with only the treatment effect on weight having a notable impact on the incremental QALYs; however, there were no scenarios which raised the ICER above £15,000 per QALY. The PSA estimated that dapagliflozin had an 85% probability of being cost-effective at a willingness-to-pay threshold of £20,000 per QALY gained., Conclusions: Dapagliflozin in combination with metformin was shown to be a cost-effective treatment option from a UK healthcare system perspective for patients with T2DM who are inadequately controlled on metformin alone.

Objective: To assess the efficiency of the combined therapy with metformin and dapagliflozin, a new oral anti-diabetic drug with an insulin-independent mechanism of action, in the treatment of type-2 diabetes mellitus (T2DM) compared to DPP4 inhibitors, sulphonylureas and thiazolidindiones, also combined with metformin., Design: Cost-effectiveness analysis using a discrete event simulation model based on the results of the available clinical trials and considering patient's entire life as time horizon., Setting: National Health System perspective., Participants: The model simulated the natural history of 30,000 patients with T2DM for each of the options compared., Main Measurements: Quality-adjusted life-years (QALY) and economic consequences of managing the disease and its complications. The analysis considered direct costs updated to 2013. A discount rate of 3% was applied to costs and health outcomes., Results: In the main analysis comparing dapagliflozin with DPP4 inhibitors, dapagliflozin resulted in a treatment option that would provide a slightly higher effectiveness (0.019 QALY) and lower overall associated costs (-€42). In the additional analyses, dapagliflozin was a cost-effective option compared with sulphonylureas and thiazolidinediones resulting in a cost per QALY gained of €3,560 and €2,007, respectively. The univariate and probabilistic sensitivity analyses confirmed the robustness of the results., Conclusions: The results of the analyses performed suggested that dapagliflozin, in combination with metformin, would be a cost-effective alternative in the Spanish context for the treatment of T2DM., (Copyright © 2014 Elsevier España, S.L.U. All rights reserved.)

Aims: To assess the cost-effectiveness of dapagliflozin, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, compared with a sulfonylurea, when added to metformin for treatment of UK people with Type 2 diabetes mellitus inadequately controlled on metformin alone., Methods: Clinical inputs sourced from a head-to-head randomized controlled trial (RCT) informed the Cardiff diabetes decision model. Risk equations developed from the United Kingdom Prospective Diabetes Study (UKPDS) were used in conjunction with the clinical inputs to predict disease progression and the incidence of micro- and macrovascular complications over a lifetime horizon. Cost and utility data were generated to present the incremental cost-effectiveness ratio (ICER) for both treatment arms, and sensitivity and scenario analyses were conducted to assess the impact of uncertainty on the final model results., Results: The dapagliflozin treatment arm was associated with a mean incremental benefit of 0.467 quality-adjusted life years (QALYs) [95% confidence interval (CI): 0.420; 0.665], with an incremental cost of £1246 (95% CI: £613; £1637). This resulted in an ICER point estimate of £2671 per QALY gained. Incremental costs were shown to be insensitive to parameter variation, with only treatment-related weight change having a significant impact on the incremental QALYs. Probabilistic sensitivity analysis determined that dapagliflozin had a 100% probability of being cost-effective at a willingness-to-pay threshold of £20,000 per QALY., Conclusions: Dapagliflozin in combination with metformin was shown to be a cost-effective treatment option compared with sulfonylurea from a UK healthcare perspective for people with Type 2 diabetes mellitus who are inadequately controlled on metformin monotherapy., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Background: Overactive bladder (OAB) is highly prevalent and is associated with considerable morbidity and reduced health-related quality of life. β3-adrenergic receptor (β3-AR) stimulation is a novel alternative to antimuscarinic therapy for OAB., Objective: The objective of this analysis was to assess the cost effectiveness of the β3-AR agonist mirabegron relative to tolterodine extended release (ER) in patients with OAB from a UK National Health Service (NHS) perspective., Methods: A Markov model was developed to simulate the management, course of disease, and effect of complications in OAB patients over a period of 5 years. Transition probabilities for symptom severity levels and probabilities of adverse events were estimated from the results of the randomised, double-blind SCORPIO trial in 1,987 patients with OAB. Other model inputs were derived from the literature and on assumptions based on clinical experience., Results: Total 5-year costs per patient were £1,645.62 for mirabegron 50 mg/day and £1,607.75 for tolterodine ER 4 mg/day. Mirabegron was associated with a gain of 0.009 quality-adjusted life-years (QALYs) with an additional cost of £37.88. The resulting incremental cost-effectiveness ratio (ICER) was £4,386/QALY gained. In deterministic sensitivity analyses in the general OAB population and several subgroups, ICERs remained below the generally accepted willingness-to-pay (WTP) threshold of £20,000/QALY gained. The probability of mirabegron 50 mg being cost effective relative to tolterodine ER 4 mg was 89.4 % at the same WTP threshold., Conclusions: Mirabegron 50 mg/day is likely to be cost effective compared with tolterodine ER 4 mg/day for adult patients with OAB from a UK NHS perspective.

Aims: The aim of this study was to assess the long-term cost-effectiveness of dapagliflozin (Forxiga(®)) added to metformin, compared with sulfonylurea (SU) added to metformin, in Nordic Type 2 diabetes mellitus (T2DM) patients inadequately controlled on metformin., Methods: Data from a 52-week clinical trial comparing dapagliflozin and SU in combination with metformin was used in a Cardiff simulation model to estimate long term diabetes-related complications in a cohort of T2DM patients. Costs and QALYs were calculated from a healthcare provider perspective and estimated over a patient's lifetime., Results: Compared with metformin+SU, the cost per QALY gained with dapagliflozin+metformin was €7944 in Denmark, €5424 in Finland, €4769 in Norway, and €6093 in Sweden. Metformin+dapagliflozin was associated with QALY gains ranging from 0.236 in Norway to 0.278 in Sweden and incremental cost ranging from €1125 in Norway to €1962 in Denmark. Results were robust across both one-way and probabilistic sensitivity analyses. Results were driven by weight changes associated with each treatment., Conclusions: Results indicate that metformin+dapagliflozin is associated with gains in QALY compared with metformin+SU in Nordic T2DM patients inadequately controlled on metformin. Dapagliflozin treatment is a cost-effective treatment alternative for Type 2 diabetes in all four Nordic countries., (Copyright © 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Objective: Economic evaluations of new diabetes therapies rely heavily upon the UK Prospective Diabetes Study (UKPDS) equations for prediction of cardiovascular events; however, concerns persist regarding their relevance to current clinical practice and appropriate use in populations other than newly diagnosed patients. This study refits the UKPDS 68 event equations, using contemporary data describing low- and intermediate-risk patients., Research Design and Methods: Anonymized patient data describing demographics, risk factors and incidence of cardiovascular and microvascular events were extracted from The Health Improvement Network (THIN) database over the 10-year period from 1 January 2000 to 31 December 2009. Following multiple imputation of missing values, accelerated failure-time Weibull regression equations were refitted to produce new coefficients for each risk group. Discriminatory performance was assessed and compared with both UKPDS 68 and UKPDS 82 risk equations, and the implication of coefficient choice within an economic evaluation was assessed using the Cardiff type 2 diabetes model., Results: When applied to patient-level data, the three sets of coefficients (UKPDS, THIN low-risk and intermediate-risk) lead to fairly consistent predictions of the 5-year risk of events. Exceptions include lower predicted rates of myocardial infarction and higher rates of ischaemic heart disease, congestive heart failure and end-stage renal disease with both sets of revised THIN coefficients compared with UKPDS. Over a modelled lifetime, the coefficients derived from the low-risk data predict fewer total cardiovascular events compared with UKPDS, while those from the intermediate-risk data predict a greater number. The areas under the receiver-operating characteristic curves demonstrated a marginal improvement in the discriminatory performance of the refitted equations. The incremental cost-effectiveness ratio associated with dapagliflozin versus sulphonylurea in addition to metformin changed from £7,708 to £7,519 and £6,906 per QALY gained, using the THIN intermediate- and low-risk coefficients, respectively., Conclusion: The results suggest that while the UKPDS equations perform best in newly diagnosed patients, they may overpredict the lifetime risk in this group and underpredict it in patients with more advanced diabetes. Implementation of the revised coefficients will result in different absolute numbers of predicted diabetes-related events; however, they are not expected to significantly affect the conclusions of economic modelling.

Objective: Diabetes mellitus type 2 (DM2) is one of the main sociosanitary problems; there are many treatments for it. Recently, it has been approved the first drug of a new family of oral hypoglycemic agents (OHA): dapagliflozin. We aimed to review the available scientific evidence on dapagliflozin, in order to analyze its effectiveness, safety and cost and to estimate its role in the current pharmacotherapy of DM2., Methods: Effectiveness and safety of dapagliflozin were analyzed by an evaluation of the scientific evidence. The cost of different OHA was calculated based on the defined daily dose (DDD) and their ex-factory prices., Results: Seven randomized clinical trials were identified: 2 monotherapy (840 patients) and 5 in combination with other hypoglycemic agents (3184 patients). In the seven trials, dapagliflozin reduced HbA1c; all were compared with placebo, unless in a trial of combination therapy in which was compared with an active drug (glipizide). The most common side effects were genitourinary infections and hypotension, although it should be taken into consideration the increase of the bladder cancer. Besides the DPP-4 inhibitors, dapagliflozin is one of the OHA more expensive (annual cost of DDD= 729.3 euros)., Conclusions: Dapagliflozin does not provide advantages over pharmacotherapy for DM2. Its lack of experience of use, the absence of significant clinical benefits and its high cost make it necessary to restrict its use., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Objective: To evaluate the use of resources and health costs in vulnerable elderly institutionalized patients with overactive bladder (OAB) treated with fesoterodine, tolterodine or solifenacin in routine medical practice., Material and Methods: A multicenter retrospective study, from the records of patients treated during 2008-2010 in three geographical locations and starting treatment with antimuscarinic (fesoterodine, solifenacin and tolterodine) for OAB. The attribute of vulnerability was based on collecting at least 3 of the Vulnerable Elders Survey criteria-13, age>75 years, poor/average age for health and difficulty in at least one daily physical activity., Main Measures: morbidity, persistence and resource use and costs. Monitoring of patients was conducted over 52 weeks. A general linear model with covariates and bootstraping (1000) at random was used to construct the 95% CI of the cost differences between drugs., Results: Records of 552 patients (50.8% women, mean age: 80.2 years) were analyzed. Treated with fesoterodine (N=58), solifenacin (N=252) or tolterodine (N=212). The use of absorbent was 20.7%, 29.4% and 33.0% (P=.186), respectively. Persistence to treatment was slightly greater with fesoterodine. The patient healthcare costs/year were lower with fesoterodine, €1,775 (1550-2014) vs. solifenacin €2,062 (1911-2223) and tolterodine €2,149 (1,978-2,307), P=.042, as a result of lower utilization visits and concomitant medication., Conclusions: Despite the potential limitations of the study, the vulnerable elderly non institutionalized patients with OAB treated with fesoterodine, compared to solifenacin or tolterodine were associated with lower resource utilization and healthcare costs., (Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.)

Background: Overactive bladder is a prevalent condition worldwide that is associated with a considerable burden, both on the patient and on society., Objective: Our objective was to assess the economic value of fesoterodine compared with tolterodine extended release (ER) for the treatment of overactive bladder (OAB) with urge urinary incontinence (UUI) in Spain and Finland., Methods: A decision-tree economic model estimated the 52-week costs and quality-adjusted life-years (QALYs) of OAB/UUI patients initiating treatment with fesoterodine 4 mg/day or tolterodine ER. Individuals were evaluated for treatment response (UUI fewer than one episode/day) and persistence at weeks 4, 12, and 24. Titration from fesoterodine 4 mg/day to 8 mg/day was permitted at week 4. At week 12, non-responders discontinued treatment permanently. Efficacy, discontinuation, and utility data were derived from four clinical trials of fesoterodine. OAB-related costs, including physician visits, laboratory tests, incontinence pads, and comorbidities (fracture, skin infection, urinary tract infections, depression, and nursing home) were also included., Results: A total of 19.5 % and 18.0 % of fesoterodine and tolterodine ER patients remained on treatment until week 52, respectively. QALYs were higher with fesoterodine than tolterodine ER (0.762 vs. 0.760). In Spain, fesoterodine treatment had higher total costs than (generic) tolterodine ER (€6,697 vs. 6,597), resulting in a cost of €15,633/QALY gained. In Finland, fesoterodine was cost saving relative to (non-generic) tolterodine ER (€7,885 vs. 8,024). Sensitivity analysis confirmed that these findings were robust to the expected price decrease for generic tolterodine ER in Finland., Conclusion: Fesoterodine is cost effective or cost saving relative to tolterodine ER for the treatment of OAB with UUI in two European countries. Payers and prescribers should consider a broad scope of costs to make informed cost-conscious choices of antimuscarinic treatment.