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.

This model provides reliable utility estimates for diabetic complications and may eliminate uncertainty in cost-effectiveness analyses of treatment. These data also provide a novel way of comparing the value of treatments that have multiple effects.

BackgroundType 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.MethodsThe 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.ResultsCompared 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.ConclusionsDapagliflozin 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.

Dapagliflozin in combination with insulin was estimated to be a cost-effective treatment option for patients with T2DM whose insulin treatment regimen does not provide adequate glycaemic control in a Dutch healthcare setting.

The results of this analysis quantify the QALY decrement that may result from adverse therapy effects. The beneficial effects of improved glycaemic control on QALYs may be offset by characteristic treatment-specific adverse effects, such as weight gain and hypoglycaemia frequency.