Cost‐effectiveness of second‐line empagliflozin versus liraglutide for type 2 diabetes in the United States

Abstract

Aim: To estimate the cost-effectiveness of sequential use of the sodium-glucose cotransporter-2 inhibitor empagliflozin and glucagon-like peptide-1 receptor agonist liraglutide after metformin in patients with type 2 diabetes (T2D) from the US payer perspective.Materials and Methods: An economic simulation model with a lifetime horizon was developed to estimate T2D-related complications (including cardiovascular[CV] death, myocardial infarction, stroke, and renal outcomes) using EMPA-REG OUTCOME data or UK Prospective Diabetes Study risk equations, in patients with or without a history of cardiovascular disease (CVD), respectively. Evidence synthesis methods were used to provide effectiveness inputs for empagliflozin and liraglutide. Population characteristics, adverse event rates, treatment escalation, costs ($2019), and utilities (both discounted 3%/year) were taken from US sources.Results: Compared with second-line liraglutide in the overall T2D population, second-line empagliflozin was dominant as it was associated with lower total lifetime cost ($11 244/patient less) and resulted in a quality-adjusted life-year (QALY) gain (0.32/patient). Second-line empagliflozin was associated with reductions in CV death (by 5%) and lower cumulative complication rates in patients with CVD (by 2%), relative to second-line liraglutide. These findings were consistent among patients with co-morbid CVD, with gains in incremental QALYs (0.43/ patient) and lower lifetime cost (by $10 175/patient) relative to second-line liraglutide. Scenario analyses consistently showed dominance for second-line empagliflozin. Conclusion:For patients with T2D, use of second-line empagliflozin combined with metformin was a dominant strategy for US payers, associated with extended survival, improved QALYs, and lower costs compared with second-line liraglutide.

Cost‐effectiveness of sodium‐glucose cotransporter‐2 inhibitors versus dipeptidyl peptidase‐4 inhibitors among patients with type 2 diabetes with and without established cardiovascular diseases: A model‐based simulation analysis using 10‐year real‐world data and targeted literature review

“…cost-effective or cost-saving) in individuals with T2D have been reported in previous studies. [32][33][34] This CEA specifically focused on the use of SGLT2is versus DPP4is and the results are comparable with those in the existing literature obtained from the targeted literature review (Table S7 for detailed literature review procedures, Figure S3 for the flow of article selection), which showed that the use of SGLT2is versus DPP4is for T2D is cost-effective [13][14][15][17][18][19] or even cost-saving. 12,16,20 Details of individual study characteristics and ICER results were summarized in Table S8 and Figure S4, respectively.…”

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

“…Other studies from the UK, 22,23 Greece 24 and the United States 25 have concluded that empagliflozin is costeffective in people with T2D and eCVD compared with SoC, or to comparator products such as semaglutide, 26 dapagliflozin, 27 sitagliptin 25 and liraglutide. 28 Support for implementation of empagliflozin was also found in a Swedish 5-year budget impact study based on register data of 5500 people with T2D and eCVD, which estimated a cost per quality-adjusted life year (QALY) of 8100 euros (EUR). 29 However, studies estimating the impact of alternate levels of implementation of SGLT-2 inhibitors in line with treatment recommendations using model simulations have not yet been conducted in a Swedish context.…”

“…Studies evaluating short term (3‐5 years) budget impact of empagliflozin as add‐on to SoC for the treatment of T2D with a history of CVD and/or increased risk of CVD from, for example, Greece, 18 Italy, 19 the UK 20 and South Africa, 21 have indicated both clinical benefits and cost savings. Other studies from the UK, 22,23 Greece 24 and the United States 25 have concluded that empagliflozin is cost‐effective in people with T2D and eCVD compared with SoC, or to comparator products such as semaglutide, 26 dapagliflozin, 27 sitagliptin 25 and liraglutide 28 …”

The challenges and pitfalls of incorporating evidence from cardiovascular outcomes trials in health economic modelling of type 2 diabetes

“…Several long‐term diabetes modelling studies have included data from CVOTs in cost‐effectiveness analyses aiming to compare active interventions from multiple CVOTs. These studies provide examples of the different methodologies possible for incorporating data from CVOTs into current modelling approaches for type 2 diabetes, and include long‐term cost‐effectiveness analyses of: Liraglutide versus empagliflozin and oral semaglutide versus empagliflozin in the United Kingdom (both Ramos et al, 2020); 58,59 Liraglutide versus empagliflozin in Denmark (Ehlers et al, 2021); 60 Sitagliptin versus empagliflozin in the United States (Reifsnider et al, 2021); 61 Liraglutide versus empagliflozin in the United States (Reifsnider et al, 2022); 62 Oral semaglutide versus empagliflozin and sitagliptin in Sweden (Eliasson et al, 2022) and the United States (Institute for Clinical and Economic Review, 2019); 56,63 A 2022 update of the type 2 diabetes guidelines by NICE in the United Kingdom 57 …”

“…The two studies by Reifsnider et al, evaluating liraglutide and sitagliptin versus empagliflozin in the United States, estimated outcomes using different methods for simulated patients with and without existing cardiovascular disease, with a cardiovascular event during the patient‐level simulation resulting in a change in the method used to calculate risk. The studies used UKPDS Outcomes Model 2 risk equations to predict the incidence of diabetes‐related complications in patients without cardiovascular disease (with outcomes extrapolated from short‐term changes in surrogate outcomes), and published event‐free survival curves developed from EMPA‐REG OUTCOME data to directly estimate the incidence of complications in patients with cardiovascular disease (without any short‐term changes in surrogate outcomes applied) 61,62 . These studies were based on an original analysis by Kansal et al, developed to directly model empagliflozin versus placebo based on EMPA‐REG OUTCOME, but caution must be used when calibrating and comparing interventions from multiple CVOTs in one analysis 64 .…”