Cost-effectiveness of dapagliflozin for patients with heart failure across the spectrum of ejection fraction: A pooled analysis of DAPA-HF and DELIVER data.

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.

Cost Effectiveness of Dapagliflozin for Heart Failure Across the Spectrum of Ejection Fraction: An Economic Evaluation Based on Pooled, Individual Participant Data From the DELIVER and DAPA-HF Trials.

BACKGROUND: The sodium glucose cotransporter-2 inhibitors are guideline-recommended to treat heart failure across the spectrum of left ventricular ejection fraction; however, economic evaluations of adding sodium glucose cotransporter-2 inhibitors to standard of care in chronic heart failure across a broad left ventricular ejection fraction range are lacking. METHODS AND RESULTS: We conducted a US-based cost-effectiveness analysis of dapagliflozin added to standard of care in a chronic heart failure population using pooled, participant data from the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trials. The 3-state Markov model used estimates of transitional probabilities, effectiveness of dapagliflozin, and utilities from the pooled trials. Costs estimates were obtained from published sources, including published rebates in dapagliflozin cost. Adding dapagliflozin to standard of care was estimated to produce an additional 0.53 quality-adjusted life years (QALYs) compared with standard of care alone. Incremental cost effectiveness ratios were $85 554/QALY when using the publicly reported full (undiscounted) Medicare cost ($515/month) and $40 081/QALY, at a published nearly 50% rebate ($263/month). The addition of dapagliflozin to standard of care would be of at least intermediate value (<$150 000/QALY) at a cost of <$872.58/month, of high value (<$50 000/QALY) at <$317.66/month, and cost saving at <$40.25/month. Dapagliflozin was of at least intermediate value in 92% of simulations when using the full (undiscounted) Medicare list cost in probabilistic sensitivity analyses. Cost effectiveness was most sensitive to the dapagliflozin cost and the effect on cardiovascular death. CONCLUSIONS: The addition of dapagliflozin to standard of care in patients with heart failure across the spectrum of ejection fraction was at least of intermediate value at the undiscounted Medicare cost and may be potentially of higher value on the basis of the level of discount, rebates, and price negotiations offered. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01035255 & NCT01920711.

Cost­effectiveness of add­on dapagliflozin for heart failure with reduced ejection fraction patients without diabetes.

AIM: To evaluate the cost-effectiveness of dapagliflozin added to standard of care (SoC) versus SoC in heart failure with reduced ejection fraction (HFrEF) and without type 2 diabetes mellitus (T2DM) patients from the Qatari healthcare perspective. MATERIALS AND METHODS: A lifetime Markov model was developed to evaluate the cost-effectiveness of adding dapagliflozin to SoC based on the findings of Petrie et al. 2020, which were based on the DAPA-HF trial. The model was constructed based on four health states: "alive with no event", "urgent visit for heart failure", "hospitalization for heart failure", and "dead". The model considered 1,000 hypothetical HFrEF and without T2DM patients using 3-month cycles over a lifetime horizon. The outcome of interest was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year gained (QALY) and years of life lived (YLL). Utility and cost data were obtained from published sources. A scenario analysis was performed to replace the transition probabilities of events in people without T2DM with the transition probabilities of events irrespective of T2DM status, based on findings of the DAPA-HF trial. Sensitivity analyses were conducted to confirm the robustness of the conclusion. RESULTS: Adding dapagliflozin to SoC was estimated to dominate SoC alone, resulting in 0.6 QALY and 0.8 YLL, at a cost saving of QAR771 (USD211) per person compared with SoC alone, with total healthcare costs of QAR42,413 (USD 11,620) versus 43,184 (USD11,831) per person, respectively. When replacing the transition probabilities of events in people without T2DM with the transition probabilities of events in people irrespective of T2DM status, dapagliflozin was cost-effective at ICER of QAR5,212 (USD1,428) per QALY gained and QAR3,880 (USD1,063) per YLL. In the probabilistic sensitivity analysis, dapagliflozin combined with SoC was cost saving in over 49% of the cases and cost-effective in over 43% of the simulated cases against QALYs gained and YLL. LIMITATIONS: Data from clinical trials were used instead of local data, which may limit the local relevance. However, evidence from the local Qatari population is lacking. Also, indirect costs were not included due to a paucity of available data. CONCLUSIONS: Adding dapagliflozin to SoC is likely to be a cost-saving therapy for patients with HFrEF and without T2DM in Qatar.

Heart failure with reduced ejection fraction is a type of heart failure characterized by left ventricular ejection fraction of 40% or less. Dapagliflozin is a novel therapy for this condition, which was initially designed to treat type 2 diabetes mellitus. It is unclear whether dapagliflozin is a cost-effective option for patients with heart failure with reduced ejection fraction and without type 2 diabetes. A lifetime Markov model was developed to evaluate the cost-effectiveness of adding dapagliflozin to standard of care from the Qatari healthcare perspective. Model results suggest that adding dapagliflozin to standard of care dominated standard of care alone, resulting in a gain of 0.8 years of life lived, a gain of 0.6 quality-adjusted life-years, and a cost saving of 211 United States dollars per person.

Translating the efficacy of dapagliflozin in chronic kidney disease to lower healthcare resource utilization and costs: a medical care cost offset analysis.

AIMS: Dapagliflozin was approved for use in patients with chronic kidney disease (CKD) based on results of the DAPA-CKD trial, demonstrating attenuation of CKD progression and reduced risk of cardio-renal outcomes and all-cause mortality (ACM) versus placebo, in addition to standard therapy. The study objective was to assess the potential medical care cost offsets associated with reduced rates of cardio-renal outcomes across 31 countries and regions. MATERIALS AND METHODS: A comparative cost-determination framework estimated outcome-related costs of dapagliflozin plus standard therapy versus standard therapy alone over a 3-year horizon based on the DAPA-CKD trial. Incidence rates of end-stage kidney disease (ESKD), hospitalizations for heart failure (HHF), acute kidney injury (AKI), and ACM were estimated for a treated population of 100,000 patients. Associated medical care costs for non-fatal events were calculated using sources from a review of publicly available data specific to each considered setting. RESULTS: Patients treated with dapagliflozin plus standard therapy experienced fewer incidents of ESKD (7,221 vs 10,767; number needed to treat, NNT: 28), HHF (2,370 vs 4,684; NNT: 43), AKI (4,110 vs. 5,819; NNT: 58), and ACM (6,383 vs 8,874; NNT: 40) per 100,000 treated patients versus those treated with standard therapy alone. Across 31 countries/regions, reductions in clinical events were associated with a 33% reduction in total costs, or a cumulative mean medical care cost offset of $264 million per 100,000 patients over 3 years. LIMITATIONS AND CONCLUSIONS: This analysis is limited by the quality of country/region-specific data available for medical care event costs. Based on the DAPA-CKD trial, we show that treatment with dapagliflozin may prevent cardio-renal event incidence at the population level, which could have positive effects upon healthcare service delivery worldwide. The analysis was restricted to outcome-associated costs and did not consider the cost of drug treatments and disease management.

Chronic kidney disease (CKD) has a high clinical, economic, and societal burden and it affects approximately 8-16% of the global population. The progressive nature of CKD may lead to complications, co-morbidities, and mortality, costing healthcare systems millions and consuming a large proportion of healthcare resources. Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, has been demonstrated to slow CKD progression and reduce cardio-renal complications, as demonstrated in the DAPA-CKD trial. With the emergence of dapagliflozin as a treatment for CKD, it is important for clinicians and healthcare providers to understand how effective treatment can positively affect short-term healthcare service delivery and associated costs. This medical care cost offset modelling analysis considers a scalable population of 100,000 patients in 31 countries/regions worldwide. The analysis estimates treatment with dapagliflozin plus standard therapy to be offset by a 33% reduction in costs associated with key cardio-renal outcomes, translating to an average $264 million in cost offsets per 100,000 treated patients. This modelling analysis of pivotal trial data shows dapagliflozin could have considerable benefits to healthcare systems worldwide that are under strain from the rising burden of CKD.

Cost-utility analysis of add-on dapagliflozin in heart failure with preserved or mildly reduced ejection fraction.

AIMS: The DELIVER study demonstrates a significant improvement in cardiovascular death or hospitalization for heart failure among heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF).Cost-utility of the adjunct use of dapagliflozin to standard therapy among patients with HFpEF or HFmrEF remains unclear. METHODS AND RESULTS: A five-state Markov mode was constructed to project health and clinical outcomes of the adjunct use of dapagliflozin to standard therapy among 65-year-old patients with HFpEF or HFmrEF. A cost-utility analysis was performed based on the DELIVER study and national statistical database. The cost and utility was inflated to 2022 by the usual discount rate of 5%. The primary outcomes were total cost and quality-adjusted life-years (QALYs) per patients as well as the incremental cost-effectiveness ratio. Sensitivity analyses were also applied. Over a 15 year lifetime horizon, the average cost per patient was $7245.77 and $5407.55 in the dapagliflozin group and the standard group, along with an incremental cost of $1838.22. The average QALYs per patient was 6.00 QALYs and 5.84 QALYs in the dapagliflozin group and the standard group, along with an incremental QALYs of 0.15 QALYs, resulting in the incremental cost-effectiveness ratio of $11 865.33/QALY, which was below the willingness-to-pay (WTP) of $12 652.5/QALY. The univariate sensitivity analysis indicated the cardiovascular death in both group was the most sensitive variable. Probability sensitivity analysis revealed that when the WTP thresholds were $12 652.5/QALY and $37 957.5/QALY, the probabilities of being cost-effective with dapagliflozin as an add-on were 54.6% and 71.6%, respectively. CONCLUSIONS: From a public healthcare system perspective, the adjunct use of dapagliflozin to standard therapy among patients with HFpEF or HFmrEF generated advantages in cost-effectiveness in China at a WTP of $12 652.5/QALY, which promoted the rational use of dapagliflozin for heart failure.

Sodium-glucose cotransporter 2 inhibitors vs. sitagliptin in heart failure and type 2 diabetes: an observational cohort study.

AIMS: The effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with heart failure (HF) in routine clinical practice is not extensively studied. This study aimed to evaluate the comparative effectiveness of SGLT2i vs. sitagliptin in older adults with HF and type 2 diabetes and to investigate whether there were any differences between agents within the SGLT2i class or for reduced and preserved ejection fraction. METHODS AND RESULTS: Using Medicare claims data (April 2013 to December 2019), 16 253 SGLT2i initiators vs. 43 352 initiators of sitagliptin aged ≥65 years with type 2 diabetes and HF were included. The primary outcome was a composite of all-cause mortality, hospitalization for HF or urgent visit requiring intravenous diuretics; secondary outcomes included its individual components. Propensity score fine stratification weighted Cox regression was used to adjust for 100 pre-exposure characteristics. Mean age was 74 years; 49.8% were women. Initiation of SGLT2i vs. sitagliptin was associated with a lower risk of the primary composite outcome [adjusted hazard ratio (HR) 0.72; 95% confidence interval 0.67-0.77]. The adjusted HRs were 0.70 (0.63-0.78) for all-cause mortality, 0.64 (0.58-0.70) for hospitalization for HF, and 0.77 (0.69-0.86) for urgent visit requiring intravenous diuretics. Similar associations with the primary composite outcome were observed for all three agents within the SGLT2i class, for reduced and preserved ejection fraction, and subgroups based on demographics, comorbidities, and other HF treatments. Bias-calibrated HRs for the primary endpoint using negative and positive control outcomes ranged between 0.81 and 0.89, suggesting that the observed benefit could not be fully explained by residual confounding. CONCLUSION: In routine US clinical practice, SGLT2i demonstrated robust clinical effectiveness in older adults with HF and type 2 diabetes compared with sitagliptin, with no evidence of heterogeneity across the SGLT2i class or across ejection fraction.

Cost-Effectiveness of Dapagliflozin vs Empagliflozin for Treating Heart Failure With Reduced Ejection Fraction in the United States.

PURPOSE: Evidence suggests that adding dapagliflozin to the prior standard of care is cost-effective compared with the standard of care alone. The latest guideline by the American Heart Association/American College of Cardiology/Heart Failure Society of America now recommends the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors for patients with heart failure with reduced ejection fraction (HFrEF). However, the relative cost-effectiveness of different SGLT2 inhibitors, including dapagliflozin and empagliflozin, has not been fully characterized. Therefore, we conducted a cost-effectiveness analysis to compare dapagliflozin and empagliflozin in patients with HFrEF from the US health care perspective. METHODS: To compare the cost-effectiveness of dapagliflozin and empagliflozin in treating HFrEF, we used a state-transition Markov model. This model was used to estimate the expected lifetime costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) for both medications. The model incorporated patients who were 65 years of age at entry and simulated their health outcomes over a lifetime horizon. The perspective of the analysis was based on the US health care system. To determine the health state transition probabilities, we used a network meta-analysis. All future costs and QALYs were discounted at an annual rate of 3%, and the costs were presented in 2022 US dollars. FINDINGS: The base case analysis found that the incremental expected lifetime cost of treating patients with dapagliflozin vs empagliflozin was $37,684, resulting in an ICER of $44,763 per QALY. A price threshold analysis indicated that for empagliflozin to be the most cost-effective SGLT2 inhibitor at a willingness-to-pay threshold of $50,000 per QALY, it may require a 12% discount on its current annual prices. IMPLICATIONS: The findings of this study indicate that dapagliflozin may offer greater lifetime economic value when compared with empagliflozin. Given that the current clinical practice guideline does not recommend one SGLT2 inhibitor over the other, it is essential to implement scalable strategies to ensure affordable access to both medications. By doing so, patients and health care practitioners can make informed decisions about their treatment options without being constrained by financial barriers.

The cost-effectiveness of dapagliflozin in heart failure with preserved or mildly reduced ejection fraction: A European health-economic analysis of the DELIVER trial.

AIMS: To determine the cost-effectiveness of dapagliflozin, added to usual care, in patients with heart failure (HF) with mildly reduced or preserved ejection fraction for the UK, German and Spanish payers using detailed patient-level data from the Dapagliflozin Evaluation to Improve the LIVEs of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial. METHODS AND RESULTS: A lifetime Markov state-transition cohort model was developed. Quartiles of the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) defined health states and monthly transition count data informed transition probabilities. Multivariable generalized estimating equations captured the incidence of HF hospitalizations and urgent HF visits, while cardiovascular deaths and all-cause mortality were estimated using adjusted parametric survival models. Health state costs were assigned to KCCQ-TSS quartiles (2021 British pound [GBP]/Euro) and patient-reported outcomes were sourced from DELIVER. Future values of costs and effects were discounted according to country-specific rates. In the UK, dapagliflozin treatment was predicted to increase quality-adjusted life years (QALYs) and life-years by 0.231 and 0.354, respectively, and extend the time spent in the best quartile of KCCQ-TSS by 4.2 months. Comparable outcomes were projected for Germany and Spain. The incremental cost-effectiveness ratios were £7761, €9540 and €5343/QALY in the UK, Germany and Spain, respectively. According to regional willingness-to-pay thresholds, 91%, 89% and 92% of simulations in the UK, Germany and Spain, respectively, were cost-effective following probabilistic sensitivity analyses. CONCLUSION: Dapagliflozin, added to usual care, is very likely cost-effective for HF with mildly reduced or preserved ejection fraction in several European countries.

Effect of Dapagliflozin Versus Empagliflozin on Cardiovascular Death in Patients with Heart Failure Across the Spectrum of Ejection Fraction: Cost per Outcome Analysis.

BACKGROUND: Dapagliflozin and empagliflozin have shown clinical benefits in patients with heart failure (HF). Their comparative monetary value remains undetermined, and we therefore sought to compare the cost-per-outcome implications of utilizing dapagliflozin versus empagliflozin to prevent cardiovascular death (CVD) in patients with HF across the spectrum of ejection fraction. METHODS: We estimated the cost needed to treat (CNT) to prevent one CVD with either dapagliflozin or empagliflozin. CNT was estimated by multiplying the annualized number needed to treat (aNNT) by the annual cost of therapy. The aNNTs were calculated based on data from the DAPA-HF and DELIVER trials for dapagliflozin, and the EMPEROR-Reduced and EMPEROR-Preserved trials for empagliflozin. Drug costs were calculated as 75% of the 2022 US National Average Drug Acquisition Cost. RESULTS: The aNNT to prevent one event of CVD was 110 (95% confidence interval [CI] 58-∞) for dapagliflozin in a pooled analysis of DAPA-HF and DELIVER versus 204 (95% CI 71-∞) for empagliflozin in a pooled analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials. The annual costs of therapy were $4807 and $4992, respectively. The corresponding CNTs were $528,770 (95% CI $278,806-∞) for dapagliflozin and $1,018,368 (95% CI $354,432-∞) for empagliflozin. This remained consistent in Europe, using the price estimates in Germany, with CNT (€77,490 for dapagliflozin and €143,708 for empagliflozin). CONCLUSION: In incorporating data from all four outcomes trials of sodium-glucose cotransporter 2 inhibitors, dapagliflozin provides better monetary value for preventing CVD events in patients with HF across the spectrum of ejection fraction.

Projecting the potential cost-effectiveness of dapagliflozin for chronic kidney disease in Kuwait.

INTRODUCTION: In 2019, the prevalence of dialysis in Kuwait were 465 patient/million population, while the annual mortality rate among dialysis patients reached 12%. To improve resource allocation within the health care system, a cost-effectiveness model was conducted from a societal perspective to assess the cost-effectiveness of the use of dapagliflozin as an add-on-therapy against SoC (ramipril) among CKD patients with or without type-2 diabetes over their lifetime. METHODOLOGY: A Markov process model was utilized to assess the cost-effectiveness of dapagliflozin + ramipril versus ramipril alone on a cohort of patients with an eGFR of 25 to 75 mL/min/1.73, with or without type-2 diabetes and a urinary ACR of 200 to 5,000 over their lifetime. The model included nine health states: (i) the six stages of CKD representing stages 1, 2, 3a, 3b, 4 and 5; (ii)ESRD, which represents RRT as dialysis or kidney transplant and (iii) death. Most of the clinical data were captured from the DAPA-CKD study. We assumed that the mortality risk of our study was similar to DAPA-CKD. The utility data were captured from different studies. Direct medical and indirect costs were captured from local data sources. Sensitivity analyses were conducted. RESULTS: The difference in QALY between dapagliflozin + ramipril versus ramipril was 0.2. The difference in cost between the two arms was KWD -4,120 (-USD25750). Dapagliflozin + ramipril generate better QALYs and lower costs than ramipril in CKD patients. Dapagliflozin improved the outcomes and generated cost savings in CKD patients. CONCLUSION: Adoption of dapagliflozin + ramipril is considered to be a cost saving option in addition to the improvement in QALYs in CKD patients with or without type-2 diabetes due to its nephroprotective effect, regardless of the aetiology of CKD, which eventually leads to reduction of dialysis and the transplantation cost burden on the Kuwaiti health care system. This study was focussed only on DAPA-CKD cohort.

Model-based predictions on health benefits and budget impact of implementing empagliflozin in people with type 2 diabetes and established cardiovascular disease.

AIM: To perform a model-based analysis of the short- and long-term health benefits and costs of further increased implementation of empagliflozin for people with type 2 diabetes and established cardiovascular disease (eCVD) in Sweden. MATERIALS AND METHODS: The validated Institute for Health Economics Diabetes Cohort Model (IHE-DCM) was used to estimate health benefits and a 3-year budget impact, and lifetime costs per quality-adjusted life years (QALY) gained of increased implementation of adding empagliflozin to standard of care (SoC) for people with type 2 diabetes and eCVD in a Swedish setting. Scenarios with 100%/75%/50% implementation were explored. Analyses were based on 30 model cohorts with type 2 diabetes and eCVD (n = 131 412 at baseline) from national health data registers. Sensitivity analyses explored the robustness of results. RESULTS: Over 3 years, SoC with empagliflozin (100% implementation) versus SoC before empagliflozin resulted in 7700 total life years gained and reductions in cumulative incidence of cardiovascular deaths by 30% and heart failures by 28%. Annual costs increased by 15% from higher treatment costs and increased survival. Half of these benefits and costs are not yet reached with current implementation below 50%. SoC with empagliflozin yielded 0.37 QALYs per person, with an incremental cost-effectiveness ratio of 16 000 EUR per QALY versus SoC before empagliflozin. CONCLUSIONS: Model simulations using real-world data and trial treatment effects indicated that a broader implementation of empagliflozin, in line with current guidelines for treatment of people with type 2 diabetes and eCVD, would lead to further benefits even from a short-term perspective.

Cost-Effectiveness of Adding Empagliflozin to Standard Treatment for Heart Failure with Preserved Ejection Fraction Patients in China.

OBJECTIVES: Heart failure is a worldwide health problem and is the leading cause of hospitalization in older patients. Heart failure with preserved ejection fraction (HFpEF) accounts for about 38% of heart failure cases. The latest EMPEROR-Preserved study shows that empagliflozin can reduce the risk of hospitalization in HFpEF, but whether empagliflozin is cost-effective in HFpEF in a Chinese setting remained uninvestigated. METHODS: A simulation of lifetime horizon for a 72-year-old HFpEF patient was conducted using a Markov model. The primary outcome was incremental cost-effectiveness ratio (ICER), expressed as incremental costs per quality-adjusted life-year (QALY). Three times the per capita GDP of China was set as the willingness-to-pay (WTP) threshold. Empagliflozin was considered cost-effective if the ICER was below the WTP threshold, otherwise it would be regarded as not cost-effective. One-way sensitivity and probabilistic sensitivity analysis (PSA) were used to assess uncertainty. RESULTS: After a simulation of lifetime horizon, a 72-year-old HFpEF patient is expected to have an expected QALY of 4.80 in the empagliflozin group, and 4.67 QALY with standard treatment. The costs of empagliflozin and standard treatment are 34,987 (US$5423) and 27,027 (US$4189) Chinese Yuan (CNY), respectively, with an ICER of 63,746 (US$9881)/QALY, lower than the WTP threshold. One-way sensitivity and PSA show that our results are robust. CONCLUSION: In Chinese HFpEF patients, adding empagliflozin to standard treatment is cost-effective, but studies based on real-world data are needed.

Comparative Assessment of the Long-Term Effectiveness and Safety of Dapagliflozin and Empagliflozin as Add-on Therapy to Hypoglycemic Drugs in Patients with Type 2 Diabetes.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce blood glucose, blood pressure, and body weight in patients with type 2 diabetes (T2D). However, the comparative long-term effectiveness and safety of SGLT2i among similar drugs, administered at different doses, have not been assessed. In this study, we compared the long-term effectiveness and safety of SGLT2i (dapagliflozin versus empagliflozin) as add-on therapy to hypoglycemic agents in T2D patients. Methods: This study was a single-center, 3-year, retrospective, observational study. For all patients in the study, drugs were evaluated for safety by documenting adverse drug reactions. The primary effectiveness was evaluated as the difference between hemoglobin A1c (HbA1c) values obtained at baseline and those obtained after 36 months of treatment. The proportion of participants with HbA1c levels <7.0% and <6.5% was also analyzed. Results: In total, 680 patients were enrolled in this study. Using propensity score matching, 234 patients each from the dapagliflozin and empagliflozin groups were selected based on patient characteristics. After 36 months of treatment, clinical parameters (including HbA1c, fasting plasma glucose, alanine aminotransferase, triglyceride levels, body weight, and systolic blood pressure) decreased significantly in these groups. The changes from the baseline for the physiological values and clinical parameters did not vary among the different dose groups of SGLT2i. The incidence of adverse drug reactions was approximately 7-8%. All patients with observed serious adverse reactions were hospitalized for urinary tract infections. Conclusion: Our study showed that the long-term continuous use of either dapagliflozin or empagliflozin as add-on therapy to hypoglycemic drugs for T2D patients is synergistically effective for lowering blood glucose, reducing body weight, and stabilizing blood pressure. Additionally, there was no significant difference in efficacy between dapagliflozin and empagliflozin, even with the administration of different doses of these agents.

The Cost-Effectiveness of Oral Semaglutide in Spain: A Long-Term Health Economic Analysis Based on the PIONEER Clinical Trials.

INTRODUCTION: Novel glucagon-like peptide-1 (GLP-1) receptor agonist oral semaglutide has demonstrated greater improvements in glycated hemoglobin (HbA1c) and body weight versus oral medications empagliflozin and sitagliptin, and injectable GLP-1 analog liraglutide, in the PIONEER clinical trial program. Based on these data, the present analysis aimed to evaluate the long-term cost-effectiveness of oral semaglutide versus empagliflozin, sitagliptin and liraglutide in Spain. METHODS: Outcomes were projected over patients' lifetimes using the IQVIA CORE Diabetes Model (v9.0), discounted at 3.0% annually. Cohort characteristics and treatment effects were sourced from PIONEER 2 and 4 for the comparisons of oral semaglutide 14 mg versus empagliflozin 25 mg and liraglutide 1.8 mg, respectively, and PIONEER 3 for oral semaglutide 7 and 14 mg versus sitagliptin 100 mg. Costs were accounted from a healthcare payer perspective in 2020 euros (EUR). Patients were assumed to receive initial therapies until HbA1c exceeded 7.5% and then treatment-intensified to basal insulin. RESULTS: Oral semaglutide 14 mg was associated with improvements in quality-adjusted life expectancy of 0.13, 0.19 and 0.06 quality-adjusted life years (QALYs) versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg, respectively, with direct costs EUR 168 higher versus empagliflozin and EUR 236 and 1415 lower versus sitagliptin and liraglutide, respectively. Oral semaglutide 14 mg was associated with an incremental cost-effectiveness ratio (ICER) of EUR 1339 per QALY gained versus empagliflozin and was considered dominant (clinically superior and cost saving) versus sitagliptin and liraglutide. Additional analyses demonstrated that oral semaglutide 7 mg was associated with improvements of 0.11 QALYs and increased costs of EUR 226 versus sitagliptin and was therefore associated with an ICER of EUR 2011 per QALY gained. CONCLUSION: Oral semaglutide 14 mg was dominant versus sitagliptin and liraglutide, and cost-effective versus empagliflozin, for the treatment of type 2 diabetes in Spain.

Cost-effectiveness evaluation of add-on dapagliflozin for heart failure with reduced ejection fraction from perspective of healthcare systems in Asia-Pacific 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.

Cost-effectiveness of Dapagliflozin for Treatment of Patients With Heart Failure With Reduced Ejection Fraction.

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.

Usefulness of Sodium-Glucose Cotransporter 2 Inhibitors for Primary Prevention of Heart Failure in Patients With Type 2 Diabetes Mellitus.

The sodium-glucose cotransporter 2 inhibitors (SGLT2i) empagliflozin, canagliflozin, and dapagliflozin reduce the risk of heart failure (HF) events in patients with diabetes mellitus (DM) at high risk for HF. Differences in HF outcomes between SGLT2i were demonstrated in a recent-published meta-analysis. Nevertheless, comparative cost-effectiveness analyses of SGLT2i provided for this indication have not been published yet. Therefore, we aimed to provide a preceding economic comparison of the costs required for improving HF outcomes by these three SGLT2i. The primary outcome was the cost needed to treat (CNT) to prevent one event of hospitalization for HF or cardiovascular mortality. CNT is calculated by multiplying the annualized number needed to treat to prevent one event by the annual cost of therapy. Clinical outcome data were extracted from pre-specified cohorts of HF-naïve patients in the pivotal randomized controlled trials (RCTs). Costs of interventions were estimated as 75% of the US National Average Drug Acquisition Cost listing. Sensitivity analysis was performed to mitigate differences between the RCT's populations. We figured the CNT for the primary prevention of HF events in DM patients to be $542,328 ($409,044-$905,412) for empagliflozin, $2,347,488 ($1,066,208-∞) for canagliflozin and $2,128,374 ($1,204,740-$48,140,518) for dapagliflozin. Sensitivity analysis confirmed the cost benefit of empagliflozin. Our findings suggest that between the available SGLT2i, the cost of primary prevention of HF in patients with DM at high risk for HF is lowest with empagliflozin. These findings may help choose an SGLT2i until head-to-head RCTs, and comprehensive cost-effective analyses for this indication are available.