Dataset Information

Cost-Effectiveness Analysis of Empagliflozin in Comparison to Sitagliptin and Saxagliptin Based on Cardiovascular Outcome Trials in Patients with Type 2 Diabetes and Established Cardiovascular Disease.

ABSTRACT:

Introduction

In the cardiovascular outcome trials (CVOT) EMPA-REG OUTCOME, TECOS and SAVOR-TIMI 53, empagliflozin [sodium/glucose cotransporter 2 (SGLT2) inhibitor], sitagliptin and saxagliptin [both dipeptidyl peptidase 4 (DPP4) inhibitors] + standard of care (SoC) were compared to SoC in patients with type 2 diabetes and established cardiovascular disease (CVD). This study assessed the cost-effectiveness (CE) of empagliflozin + SoC in comparison to sitagliptin + SoC and saxagliptin + SoC based on the respective CVOT.

Methods

The IQVIA Core Diabetes Model (CDM) was calibrated to reproduce the CVOT outcomes. EMPA-REG OUTCOME baseline characteristics and CVOT specific treatment effects on risk factors for cardiovascular disease [glycated haemogloblin A1c (HbA1c), body mass index (BMI), blood pressure, lipids] were applied. Three-year observed cardiovascular events of empagliflozin + SoC versus sitagliptin + SoC and saxagliptin + SoC were derived from EMPA-REG OUTCOME and an indirect treatment comparison. Relative risk (RR) adjustments to calibrate the CDM were estimated after consecutive attempts of running the model until the observed and CDM-predicted outcomes matched closely. The drug-specific treatment effects were considered up until treatment switch (when HbA1c reached 8.5%), after which, the United Kingdom Prospective Diabetes Study (UKPDS) 82 risk equations predicted events based on co-existing risk factors and treatment intensification to basal-bolus insulin were applied. The analysis was conducted from the perspective of the UK National Health Service. Costs and quality of life data were derived from UK national sources and published literature. A 50-year time horizon and discount rate of 3.5% were applied.

Results

The CDM projected quality-adjusted life years (QALYs) of 6.408, 5.917 and 5.704 and total costs of 50,801 GBP, 47,627 GBP and 48,071 GBP for empagliflozin + SoC, sitagliptin + SoC and saxagliptin + SoC, respectively. The incremental CE ratio (ICER) of empagliflozin + SoC versus sitagliptin + SoC and saxagliptin + SoC was 6464 GBP/QALY and 3878 GBP/QALY, respectively. One-way and probabilistic sensitivity analyses demonstrated the robustness of the results.

Conclusion

Results suggest that empagliflozin + SoC is cost-effective compared to sitagliptin + SoC and saxagliptin + SoC at a willingness to pay threshold of 20,000 GBP/QALY.

Funding

Boehringer Ingelheim International GmbH.

SUBMITTER: Ramos M

PROVIDER: S-EPMC6848565 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIn several cardiovascular outcome trials (CVOTs), empagliflozin (SGLT-2 inhibitor), sitagliptin (DPP-4 inhibitor) and liraglutide (GLP-1 receptor agonist) + standard of care (SoC) were compared to SoC in patients with type 2 diabetes and established cardiovascular disease (CVD). This study assessed the cost-effectiveness (CE) of empagliflozin + SoC in comparison to sitagliptin + SoC and liraglutide + SoC based on the respective CVOT.MethodsThe IQVIA Core Diabetes Model (CDM) was calibrated to reproduce the CVOT outcomes. EMPA-REG OUTCOME baseline characteristics and CVOT specific treatment effects on risk factors for cardiovascular disease (HbA1c, BMI, blood pressure, lipids) were applied. Three-year observed cardiovascular events of empagliflozin + SoC versus sitagliptin + SoC and liraglutide + SoC were derived from EMPA-REG OUTCOME and an indirect treatment comparison. Relative risk adjustments to calibrate the CDM were obtained after a trial and error process to match as closely the observed and CDM-predicted outcomes. The drug-specific treatment effects were considered up until HbA1c reached 8.5% and treatment switch occurred. After this switch, the United Kingdom Prospective Diabetes Study 82 risk equations predicted events based on co-existing risk factors and treatment intensification to basal bolus insulin were applied. The analysis was conducted from the perspective of the Chinese healthcare system applying 3% discounting. The time horizon was lifelong.ResultsEmpagliflozin + SoC provides additional Quality Adjusted Life years (QALY + 0.564) for an incremental cost of 42,497RMB (US$6053) compared to sitagliptin + SoC, resulting in an Incremental Cost Utility Ratio of 75,349RMB (US$10,732), thus below the willingness-to-pay threshold of 212,676RMB, corresponding to three times the Gross Domestic Product in China (2019). Compared to liraglutide + SoC, empagliflozin + SoC use leads to 0.211QALY gained and cost savings of 71,427RMB (US$10,173) and is as such dominant. Scenario and probabilistic sensitivity analyses demonstrated the robustness of the results.ConclusionResults suggest that empagliflozin + SoC is cost-effective compared to sitagliptin + SoC and liraglutide + SoC at a willingness-to-pay threshold of 212,676RMB ($30,292)/QALY.

Project description:IntroductionThe increasing financial burden associated with diabetes treatment presents a challenge to healthcare systems worldwide. Recently, clinical guidelines have focussed on patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) and recommend a sodium-glucose co-transporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist as second-line treatment after metformin or independently of baseline glycated haemogloblin A1c (HbA1c). In Danish clinical guidelines, empagliflozin and liraglutide are highlighted owing to their positive impact on mortality. Thus, this study aimed to assess the cost-effectiveness of empagliflozin plus standard of care (SoC) versus liraglutide plus SoC in Danish patients with T2D and established CVD using a lifetime and 5-year horizon.MethodsThe IQVIA Core Diabetes Model (CDM) was calibrated to reproduce the clinical event rates observed in the cardiovascular outcome trial EMPA-REG OUTCOME. Network meta-analysis provided the relative risks for cardiovascular outcomes with empagliflozin versus liraglutide. Microvascular outcomes were predicted by standard CDM risk equations. The relative treatment effect was assumed for 9 years after which treatment was switched to basal-bolus therapy. The CDM was populated with Danish costs of events and drug costs at price-level 2019. Discounting of 4% was applied.ResultsOver a lifetime horizon, CDM projected 9.858 and 9.667 life years, 6.162 and 5.976 quality-adjusted life years (QALY) and DKK 478,026 (€64,079) and DKK 500,025 (€67,027) in total costs for empagliflozin plus SoC and liraglutide plus SoC, respectively. For a 5-year horizon, the results were 4.189 and 4.140 life years, 2.746 and 2.655 QALY, as well as DKK 123,413 (€16,543) and DKK 161,783 (€21,687), respectively. Empagliflozin was the dominant treatment alternative. Sensitivity analyses showed the robustness of these results.ConclusionThe cost-effectiveness analysis suggests that empagliflozin plus SoC is dominant compared to liraglutide plus SoC in Denmark over both lifetime and 5-year horizons.

Project description:INTRODUCTION:The PIONEER trial programme showed that, after 52 weeks, the novel oral glucagon-like peptide-1 (GLP-1) analogue semaglutide 14 mg was associated with significantly greater reductions in glycated haemoglobin (HbA1c) versus a sodium-glucose cotransporter-2 inhibitor (empagliflozin 25 mg), a dipeptidyl peptidase-4 inhibitor (sitagliptin 100 mg) and an injectable GLP-1 analogue (liraglutide 1.8 mg). The aim of the present analysis was to assess the long-term cost-effectiveness of oral semaglutide 14 mg versus each of these comparators in the UK setting. METHODS:Analyses were performed from a healthcare payer perspective using the IQVIA CORE Diabetes Model, in which outcomes were projected over patient lifetimes (50 years). Baseline cohort characteristics and treatment effects were based on 52-week data from the PIONEER 2, 3 and 4 randomised controlled trials, comparing oral semaglutide with empagliflozin, sitagliptin and liraglutide, respectively. Treatment switching occurred when HbA1c exceeded 7.5% (58 mmol/mol). Utilities, treatment costs and costs of diabetes-related complications (in pounds sterling [GBP]) were taken from published sources. The acquisition cost of oral semaglutide was assumed to match that of once-weekly semaglutide. RESULTS:Oral semaglutide was associated with improvements in quality-adjusted life expectancy of 0.09 quality-adjusted life years (QALYs) versus empagliflozin, 0.20 QALYs versus sitagliptin and 0.07 QALYs versus liraglutide. Direct costs over a patient's lifetime were GBP 971 and GBP 963 higher with oral semaglutide than with empagliflozin and sitagliptin, respectively, but GBP 1551 lower versus liraglutide. Oral semaglutide was associated with a reduced incidence of diabetes-related complications versus all comparators. Therefore, oral semaglutide 14 mg was associated with incremental cost-effectiveness ratios of GBP 11,006 and 4930 per QALY gained versus empagliflozin 25 mg and sitagliptin 100 mg, respectively, and was more effective and less costly (dominant) versus liraglutide 1.8 mg. CONCLUSION:Oral semaglutide was cost-effective versus empagliflozin and sitagliptin, and dominant versus liraglutide, for the treatment of type 2 diabetes in the UK.

Project description:ObjectiveThe aim of this study was to assess the cost effectiveness of oral semaglutide versus other oral glucose-lowering drugs for the management of type 2 diabetes (T2D) in Sweden.MethodsThe Swedish Institute for Health Economics Diabetes Cohort Model was used to assess the cost effectiveness of oral semaglutide 14 mg versus empagliflozin 25 mg and oral semaglutide 14 mg versus sitagliptin 100 mg, using data from the head-to-head PIONEER 2 and 3 trials, respectively, in which these treatments were added to metformin (± sulphonylurea). Base-case and scenario analyses were conducted. Robustness was evaluated with deterministic and probabilistic sensitivity analyses.ResultsIn the base-case analyses, greater initial lowering of glycated haemoglobin levels with oral semaglutide versus empagliflozin and oral semaglutide versus sitagliptin, respectively, resulted in reduced incidences of micro- and macrovascular complications and was associated with lower costs of complications and indirect costs. Treatment costs were higher for oral semaglutide, resulting in higher total lifetime costs than with empagliflozin (Swedish Krona [SEK] 1,245,570 vs. 1,210,172) and sitagliptin (SEK1,405,789 vs. 1,377,381). Oral semaglutide was shown to be cost effective, with an incremental cost-effectiveness ratio (ICER) of SEK239,001 per quality-adjusted life-year (QALY) compared with empagliflozin and SEK120,848 per QALY compared with sitagliptin, from a payer perspective. ICERs were lower at SEK191,721 per QALY compared with empagliflozin and SEK95,234 per QALY compared with sitagliptin from a societal perspective. Results were similar in scenario analyses that incorporated cardiovascular effects, and also in sensitivity analyses.ConclusionsIn a Swedish setting, oral semaglutide was cost effective compared with empagliflozin and sitagliptin for patients with T2D inadequately controlled on oral glucose-lowering drugs.Trial registrationClinicalTrials.gov: NCT02863328 (PIONEER 2; registered 11 August 2016) and NCT02607865 (PIONEER 3; registered 18 November 2015).

Project description:ObjectiveThe aim was to evaluate the cost-effectiveness of oral and subcutaneous semaglutide versus other oral glucose-lowering drugs (i.e., empagliflozin, canagliflozin, and sitagliptin) for the management of type 2 diabetes (T2D) in Denmark using clinically relevant treatment intensification rules.MethodsA Markov-type cohort model for evaluating the cost-effectiveness of treatment pathways for T2D was used to produce cost-effectiveness estimates based on four head-to-head trials. Evidence from PIONEER 2 and 3 trials was used to evaluate the cost-effectiveness of oral semaglutide vs. empagliflozin and sitagliptin. Evidence from SUSTAIN 2 and 8 trials was used to evaluate the cost-effectiveness of subcutaneous semaglutide vs. sitagliptin and canagliflozin. Base case analyses used trial product estimands of treatment efficacy to avoid the confounding effects of rescue medication use during trials. Deterministic scenario analyses and probabilistic sensitivity analyses were conducted to assess robustness of cost-effectiveness estimates.ResultsSemaglutide-based treatment regimens were consistently associated with higher lifetime diabetes treatment costs, lower costs of complications, and higher lifetime accumulated QALYs. The PIONEER 2 analysis estimated the cost-effectiveness of oral semaglutide vs. empagliflozin was DKK 150,618/QALY (€20,189). The PIONEER 3 analysis estimated the cost-effectiveness of oral semaglutide vs. sitagliptin was DKK 95,093/QALY (€12,746). The SUSTAIN 2 analysis estimated the cost-effectiveness of subcutaneous semaglutide vs. sitagliptin was DKK 79,982/QALY (€10,721). The SUSTAIN 8 analysis estimated the cost-effectiveness of subcutaneous semaglutide vs. canagliflozin was DKK 167,664/QALY (€22,474).ConclusionsDaily oral and weekly subcutaneous semaglutide are likely to both increase cost and health benefits, but are likely to do so under commonly considered cost-effectiveness thresholds.Trial registrationsClinicaltrials.gov: NCT02863328 (PIONEER 2; registered August 11, 2016); NCT02607865 (PIONEER 3; registered November 18, 2015); NCT01930188 (SUSTAIN 2; registered August 28, 2013); NCT03136484 (SUSTAIN 8; registered May 2, 2017).