The Cost-Effectiveness of Subcutaneous Semaglutide Versus Empagliflozin in Type 2 Diabetes Uncontrolled on Metformin Alone in Denmark.

INTRODUCTION: International and Danish guidelines recommend the use of glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors already in second line in the management of type 2 diabetes (T2D). The objective of this study was to evaluate the long-term cost-effectiveness (CE) of subcutaneous (SC) semaglutide (GLP-1 RA) versus empagliflozin (SGLT-2 inhibitor) in individuals with T2D uncontrolled on metformin alone from a Danish payer's perspective. METHODS: Cost-effectiveness analyses (CEA) were conducted from a Danish payer's perspective, using the IQVIA Core Diabetes model (CDM 9.5), with a time horizon of 50 years and an annual discount of 4% on costs and effects. Patients received either SC semaglutide or empagliflozin, in addition to metformin, until HbA1c threshold of 7.5% (58 mmol/mol) was reached, following which treatment intensification with insulin glargine in addition to empagliflozin or SC semaglutide plus metformin was considered. Baseline cohort characteristics and treatment effects were sourced from a published CEA. Utilities and cost of diabetes-related complications were also obtained from published sources. Treatment costs were derived from Danish official sources. Scenario analyses were also performed to test the accuracy of the base case results. RESULTS: Individuals with T2D on SC semaglutide plus metformin gained 0.065 life-years (LYs) and 0.130 quality-adjusted LYs (QALYs), respectively, at an incremental cost of DKK 96,923 (€ 13,031) compared to empagliflozin plus metformin, resulting in an incremental cost-effectiveness ratio (ICER) of DKK 745,561(€ 100,239) per QALY gained. The probabilistic sensitivity analysis (PSA) results showed that the SC semaglutide plus metformin was cost-effective in 19% of simulations assuming a willingness-to-pay (WTP) threshold of DKK 357,100 (€ 48,011)/QALY gained. Duration of therapy with SC semaglutide seems the key driver of results. CONCLUSION: The current analyses suggest that SC semaglutide plus metformin is not cost-effective compared to empagliflozin plus metformin from a Danish payer's perspective.

The cost-effectiveness of oral semaglutide versus empagliflozin in Type 2 diabetes in Denmark.

Aim: To evaluate the cost-effectiveness of oral semaglutide+metformin versus empagliflozin+metformin in people with Type 2 diabetes uncontrolled on msetformin alone. Materials and methods: The IQVIA Core Diabetes Model was populated with efficacy data from a head-to-head study between oral semaglutide+metformin and empagliflozin+metformin. Danish costs and quality-of-life data were sourced from literature. Price per day was Danish Krone (DKK) 25.53 for oral semaglutide and DKK11.40 for empagliflozin. Discounting was fixed at 4%. Scenario and sensitivity analyses were performed. Results: Over a lifetime, Core Diabetes Model projected 8.78 and 8.75 quality-adjusted life-years and a total cost of DKK 447,633 and DKK 387,786, thereby generating an incremental cost-effectiveness ratio of DKK 1,930,548 for oral semaglutide+metformin versus empagliflozin+metformin. Scenario and sensitivity analyses showed the robustness of the outcomes. Duration of treatment with oral semaglutide is the key driver of the analyses. Conclusion: Oral semaglutide+metformin seems not cost effective versus empagliflozin+metformin in patients uncontrolled on metformin in Denmark.

Healthcare Resource Utilization and Costs for Empagliflozin Versus Glucagon-Like Peptide-1 Receptor Agonists in Routine Clinical Care in Denmark.

INTRODUCTION: The sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin has shown reductions in major adverse cardiac events similar to glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, evidence is limited about how these therapies compare regarding overall healthcare resource utilization and costs in routine clinical care. METHODS: We conducted a comparative cohort study based on linked prospective healthcare databases for the entire population of Denmark during 2015-2018. We included 13,747 new users of empagliflozin and 13,249 new users of GLP-1RAs. Propensity scores were applied to balance potential confounders across the two treatment groups through inverse probability treatment weighting (IPTW). We assessed directly referable costs per person-year associated with healthcare resource utilization (inpatient, emergency room, and outpatient clinic hospital care, primary care health services, and prescription medication costs at pharmacies) among drug initiators while on-treatment. RESULTS: The two IPTW cohorts were well balanced at baseline (median age 61 years, 60% men, diabetes duration 6.7 years, 19% with pre-existing ischemic heart disease, 8% with pre-existing cerebrovascular disease), with similar healthcare costs in the previous year. During follow-up, average on-treatment costs per person-year were very similar among empagliflozin and GLP-1 RA initiators for the following services: inpatient hospitalizations (13,565 DKK versus 13,275 DKK), hospital outpatient clinic visits (12,007 DKK versus 12,152 DKK), emergency room visits (370 DKK versus 399 DKK), and primary care services (4108 DKK versus 4302 DKK). Total costs for any prescription drugs were clearly lower for empagliflozin initiators than for GLP-1 RA initiators (8946 DKK versus 14,029 DKK). In sum, overall healthcare costs on-treatment were lower for empagliflozin initiators (38,995 DKK per person-year) than for GLP-1RA initiators (44,157 DKK per person-year). CONCLUSIONS: In this nationwide population-based cohort study, average healthcare costs after drug initiation and while on treatment were lower for empagliflozin initiators than for GLP-1RAs initiators, driven by lower drug costs. REGISTRATION: The study protocol and analysis plan have been registered on the website of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) ( http://www.encepp.eu/encepp/viewResource.htm?id=37726 , first protocol registration 4 June 2019), and on clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT03993132 , first posted 20 June 2019).

The Cost-Effectiveness of Empagliflozin Versus Liraglutide Treatment in People with Type 2 Diabetes and Established Cardiovascular Disease.

INTRODUCTION: The 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. METHODS: The 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. RESULTS: Over 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. CONCLUSION: The cost-effectiveness analysis suggests that empagliflozin plus SoC is dominant compared to liraglutide plus SoC in Denmark over both lifetime and 5-year horizons.

Cardiovascular Events, Acute Hospitalizations, and Mortality in Patients With Type 2 Diabetes Mellitus Who Initiate Empagliflozin Versus Liraglutide: A Comparative Effectiveness Study.

Background In cardiovascular outcome trials, the sodium glucose cotransporter 2 inhibitor empagliflozin and glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide caused similar reductions in major adverse cardiac events (MACE). We compared clinical outcomes in routine clinical care. Methods and Results EMPLACE (Cardiovascular and Renal Outcomes, and Mortality in Danish Patients with Type 2 Diabetes Who Initiate Empagliflozin Versus GLP-1RA: A Danish Nationwide Comparative Effectiveness Study) is an ongoing nationwide population-based comparative effectiveness cohort study in Denmark. For the present study, we included 14 498 new users of empagliflozin and 12 706 new users of liraglutide, 2015 to 2018. Co-primary outcomes were expanded major adverse cardiac events (stroke, myocardial infarction, unstable angina, coronary revascularization, hospitalization for heart failure [HHF], or all-cause death); HHF or all-cause death; and first HHF or first initiation of loop-diuretic therapy. Secondary outcomes included all-cause hospitalization or death. We applied propensity score balancing and Cox regression to compute adjusted hazard ratios (aHRs) in on-treatment (OT) and intention-to-treat (ITT) analyses. Cohorts were well balanced at baseline (median age 61 years, 59% men, diabetes mellitus duration 6.6 years, 30% with preexisting cardiovascular disease). During mean follow-up of 1.1 years in OT and 1.5 years in ITT analyses, empagliflozin versus liraglutide was associated with a similar rate of expanded major adverse cardiac events (OT aHR, 1.02; 95% CI, 0.91-1.14; ITT aHR, 1.06; 95% CI, 0.96-1.17), and HHF or all-cause death (OT aHR, 0.97; 95% CI, 0.85-1.11; ITT aHR, 1.02; 95% CI, 0.91-1.14); and a decreased rate of a first incident HHF or loop-diuretic initiation (OT aHR, 0.80; 95% CI, 0.68-0.94; ITT aHR, 0.87; 95% CI, 0.76-1.00), and of all-cause hospitalization or death (OT aHR, 0.93; 95% CI, 0.89-0.98; ITT aHR, 0.93; 95% CI, 0.90-0.97). Conclusions Empagliflozin and liraglutide initiators had comparable rates of expanded major adverse cardiac events, and HHF or all-cause death, whereas empagliflozin initiators had a lower rate of a first HHF or loop-diuretic initiation.