Skip to main content
Top
Published in: Diabetes Therapy 6/2019

Open Access 01-12-2019 | Sitagliptin | Original Research

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

Authors: Mafalda Ramos, Volker Foos, Anastasia Ustyugova, Nikco Hau, Pranav Gandhi, Mark Lamotte

Published in: Diabetes Therapy | Issue 6/2019

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Davies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669–701.CrossRef Davies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669–701.CrossRef
4.
go back to reference Schnell O, Rydén L, Standl E, Ceriello A, On behalf of the D&CVD EASD Study Group. Current perspectives on cardiovascular outcome trials in diabetes. Cardiovasc Diabetol. 2016;15(1):139.CrossRef Schnell O, Rydén L, Standl E, Ceriello A, On behalf of the D&CVD EASD Study Group. Current perspectives on cardiovascular outcome trials in diabetes. Cardiovasc Diabetol. 2016;15(1):139.CrossRef
6.
go back to reference McGuire DK, Alexander JH, Johansen OE, et al. Linagliptin effects on heart failure and related outcomes in individuals with type 2 diabetes mellitus at high cardiovascular and renal risk in CARMELINA. Circulation. 2019;139(3):351–61.CrossRef McGuire DK, Alexander JH, Johansen OE, et al. Linagliptin effects on heart failure and related outcomes in individuals with type 2 diabetes mellitus at high cardiovascular and renal risk in CARMELINA. Circulation. 2019;139(3):351–61.CrossRef
8.
go back to reference Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23):2247–57.CrossRef Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23):2247–57.CrossRef
9.
go back to reference Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22.CrossRef Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22.CrossRef
10.
go back to reference Zinman B, Inzucchi SE, Lachin JM, et al. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME™). Cardiovasc Diabetol. 2014;19(13):102.CrossRef Zinman B, Inzucchi SE, Lachin JM, et al. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME™). Cardiovasc Diabetol. 2014;19(13):102.CrossRef
11.
go back to reference Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.CrossRef Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.CrossRef
12.
go back to reference Fitchett D, Zinman B, Wanner C, et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. Eur Heart J. 2016;37(19):1526–34.CrossRef Fitchett D, Zinman B, Wanner C, et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. Eur Heart J. 2016;37(19):1526–34.CrossRef
13.
go back to reference Rådholm K, Figtree G, Perkovic V, et al. Canagliflozin and heart failure in type 2 diabetes mellitus. Circulation. 2018;138(5):458–68.CrossRef Rådholm K, Figtree G, Perkovic V, et al. Canagliflozin and heart failure in type 2 diabetes mellitus. Circulation. 2018;138(5):458–68.CrossRef
14.
go back to reference American Diabetes Association. Introduction: standards of Medical Care in Diabetes-2018. Diabetes Care. 2018;41:S1–2.CrossRef American Diabetes Association. Introduction: standards of Medical Care in Diabetes-2018. Diabetes Care. 2018;41:S1–2.CrossRef
16.
go back to reference Palmer AJ, Roze S, Valentine WJ, et al. The CORE Diabetes Model: projecting long-term clinical outcomes, costs and cost-effectiveness of interventions in diabetes mellitus (types 1 and 2) to support clinical and reimbursement decision-making. Curr Med Res Opin. 2004;20(Suppl 1):S5–26.CrossRef Palmer AJ, Roze S, Valentine WJ, et al. The CORE Diabetes Model: projecting long-term clinical outcomes, costs and cost-effectiveness of interventions in diabetes mellitus (types 1 and 2) to support clinical and reimbursement decision-making. Curr Med Res Opin. 2004;20(Suppl 1):S5–26.CrossRef
17.
go back to reference McEwan P, Foos V, Palmer JL, Lamotte M, Lloyd A, Grant D. Validation of the IMS CORE diabetes model. Value Health. 2014;17(6):714–24.CrossRef McEwan P, Foos V, Palmer JL, Lamotte M, Lloyd A, Grant D. Validation of the IMS CORE diabetes model. Value Health. 2014;17(6):714–24.CrossRef
18.
go back to reference Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373(3):232–42.CrossRef Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373(3):232–42.CrossRef
19.
go back to reference Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369(14):1317–26.CrossRef Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369(14):1317–26.CrossRef
20.
go back to reference Hayes AJ, Leal J, Gray AM, Holman RR, Clarke PM. UKPDS outcomes model 2: a new version of a model to simulate lifetime health outcomes of patients with type 2 diabetes mellitus using data from the 30 year United Kingdom Prospective Diabetes Study: UKPDS 82. Diabetologia. 2013;56(9):1925–33.CrossRef Hayes AJ, Leal J, Gray AM, Holman RR, Clarke PM. UKPDS outcomes model 2: a new version of a model to simulate lifetime health outcomes of patients with type 2 diabetes mellitus using data from the 30 year United Kingdom Prospective Diabetes Study: UKPDS 82. Diabetologia. 2013;56(9):1925–33.CrossRef
21.
go back to reference Kengne AP, Patel A, Marre M, et al. Contemporary model for cardiovascular risk prediction in people with type 2 diabetes. Eur J Cardiovasc Prev Rehabil. 2011;18(3):393–8.CrossRef Kengne AP, Patel A, Marre M, et al. Contemporary model for cardiovascular risk prediction in people with type 2 diabetes. Eur J Cardiovasc Prev Rehabil. 2011;18(3):393–8.CrossRef
22.
go back to reference Ahmad Kiadaliri A, Clarke PM, Gerdtham U-G, et al. Predicting changes in cardiovascular risk factors in type 2 diabetes in the post-UKPDS Era: longitudinal analysis of the Swedish National Diabetes Register. J Diabetes Res. 2013;2013:241347.CrossRef Ahmad Kiadaliri A, Clarke PM, Gerdtham U-G, et al. Predicting changes in cardiovascular risk factors in type 2 diabetes in the post-UKPDS Era: longitudinal analysis of the Swedish National Diabetes Register. J Diabetes Res. 2013;2013:241347.CrossRef
23.
go back to reference Cederholm J, Eeg-Olofsson K, Eliasson B, Zethelius B, Nilsson PM, Gudbjörnsdottir S. Risk prediction of cardiovascular disease in type 2 diabetes. Diabetes Care. 2008;31(10):2038–43.CrossRef Cederholm J, Eeg-Olofsson K, Eliasson B, Zethelius B, Nilsson PM, Gudbjörnsdottir S. Risk prediction of cardiovascular disease in type 2 diabetes. Diabetes Care. 2008;31(10):2038–43.CrossRef
24.
go back to reference Folsom AR, Chambless LE, Duncan BB, Gilbert AC, Pankow JS, Atherosclerosis Risk in Communities Study Investigators. Prediction of coronary heart disease in middle-aged adults with diabetes. Diabetes Care. 2003;26(10):2777–84.CrossRef Folsom AR, Chambless LE, Duncan BB, Gilbert AC, Pankow JS, Atherosclerosis Risk in Communities Study Investigators. Prediction of coronary heart disease in middle-aged adults with diabetes. Diabetes Care. 2003;26(10):2777–84.CrossRef
25.
go back to reference Davis WA, Knuiman MW, Davis TME. An Australian cardiovascular risk equation for type 2 diabetes: the Fremantle Diabetes Study. Intern Med J. 2010;40(4):286–92.CrossRef Davis WA, Knuiman MW, Davis TME. An Australian cardiovascular risk equation for type 2 diabetes: the Fremantle Diabetes Study. Intern Med J. 2010;40(4):286–92.CrossRef
26.
go back to reference Assmann G, Cullen P, Schulte H. Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Münster (PROCAM) study. Circulation. 2002;105(3):310–5.CrossRef Assmann G, Cullen P, Schulte H. Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Münster (PROCAM) study. Circulation. 2002;105(3):310–5.CrossRef
27.
go back to reference Balijepalli C, Shirali R, Kandaswamy P, et al. Cardiovascular safety of empagliflozin versus dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes: systematic literature review and indirect comparisons. Diabetes Ther. 2018;9(4):1491–500.CrossRef Balijepalli C, Shirali R, Kandaswamy P, et al. Cardiovascular safety of empagliflozin versus dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes: systematic literature review and indirect comparisons. Diabetes Ther. 2018;9(4):1491–500.CrossRef
28.
go back to reference Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375(4):323–34.CrossRef Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375(4):323–34.CrossRef
29.
go back to reference Riddle MC, Bolli GB, Ziemen M, et al. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 1). Diabetes Care. 2014;37(10):2755–62.CrossRef Riddle MC, Bolli GB, Ziemen M, et al. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 1). Diabetes Care. 2014;37(10):2755–62.CrossRef
33.
go back to reference Beaudet A, Clegg J, Thuresson P-O, Lloyd A, McEwan P. Review of utility values for economic modeling in type 2 diabetes. Value Health. 2014;17(4):462–70.CrossRef Beaudet A, Clegg J, Thuresson P-O, Lloyd A, McEwan P. Review of utility values for economic modeling in type 2 diabetes. Value Health. 2014;17(4):462–70.CrossRef
34.
go back to reference Bagust A, Beale S. Modelling EuroQol health-related utility values for diabetic complications from CODE-2 data. Health Econ. 2005;14(3):217–30.CrossRef Bagust A, Beale S. Modelling EuroQol health-related utility values for diabetic complications from CODE-2 data. Health Econ. 2005;14(3):217–30.CrossRef
37.
go back to reference Lamotte M, Salem A, Mettam SR, Ustyugova AV, Zhang E, Ramos M. 1292-P: projected long-term clinical benefit and cost-effectiveness of empagliflozin compared with glimepiride in patients with type 2 diabetes in China. Diabetes. 2019;68(Suppl 1):1292.CrossRef Lamotte M, Salem A, Mettam SR, Ustyugova AV, Zhang E, Ramos M. 1292-P: projected long-term clinical benefit and cost-effectiveness of empagliflozin compared with glimepiride in patients with type 2 diabetes in China. Diabetes. 2019;68(Suppl 1):1292.CrossRef
38.
go back to reference McGill JB. The SGLT2 inhibitor empagliflozin for the treatment of type 2 diabetes mellitus: a bench to bedside review. Diabetes Ther. 2014;5(1):43–63.CrossRef McGill JB. The SGLT2 inhibitor empagliflozin for the treatment of type 2 diabetes mellitus: a bench to bedside review. Diabetes Ther. 2014;5(1):43–63.CrossRef
39.
go back to reference Daacke I, Kandaswamy P, Tebboth A, Kansal A, Reifsnider O. Cost-effectiveness of empagliflozin (Jardiance) in the treatment of patients with type 2 diabetes mellitus (T2DM) in the UK based on Empa-Reg outcome data. Value Health. 2016;19(7):A673.CrossRef Daacke I, Kandaswamy P, Tebboth A, Kansal A, Reifsnider O. Cost-effectiveness of empagliflozin (Jardiance) in the treatment of patients with type 2 diabetes mellitus (T2DM) in the UK based on Empa-Reg outcome data. Value Health. 2016;19(7):A673.CrossRef
40.
go back to reference Gourzoulidis G, Tzanetakos C, Ioannidis I, et al. Cost-effectiveness of empagliflozin for the treatment of patients with type 2 diabetes mellitus at increased cardiovascular risk in Greece. Clin Drug Investig. 2018;38(5):417–26.CrossRef Gourzoulidis G, Tzanetakos C, Ioannidis I, et al. Cost-effectiveness of empagliflozin for the treatment of patients with type 2 diabetes mellitus at increased cardiovascular risk in Greece. Clin Drug Investig. 2018;38(5):417–26.CrossRef
42.
go back to reference Kansal A, Reifsnider O, Lee J, et al. Cost-effectiveness analysis of empagliflozin compared with canagliflozin or standard of care (SoC) in patients with T2DM and established cardiovascular (CV) Disease. Diabetes. 2018;67(Suppl 1):1294.CrossRef Kansal A, Reifsnider O, Lee J, et al. Cost-effectiveness analysis of empagliflozin compared with canagliflozin or standard of care (SoC) in patients with T2DM and established cardiovascular (CV) Disease. Diabetes. 2018;67(Suppl 1):1294.CrossRef
43.
go back to reference Mettam SR, Bajaj H, Kansal AR, Kandaswamy P. Cost effectiveness of empagliflozin in patients with T2DM and high CV risk in Canada. Value Health. 2016;19(7):A674.CrossRef Mettam SR, Bajaj H, Kansal AR, Kandaswamy P. Cost effectiveness of empagliflozin in patients with T2DM and high CV risk in Canada. Value Health. 2016;19(7):A674.CrossRef
44.
go back to reference Nguyen E, Coleman CI, Nair S, Weeda ER. Cost-utility of empagliflozin in patients with type 2 diabetes at high cardiovascular risk. J Diabetes Complicat. 2018;32(2):210–5.CrossRef Nguyen E, Coleman CI, Nair S, Weeda ER. Cost-utility of empagliflozin in patients with type 2 diabetes at high cardiovascular risk. J Diabetes Complicat. 2018;32(2):210–5.CrossRef
Metadata
Title
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
Authors
Mafalda Ramos
Volker Foos
Anastasia Ustyugova
Nikco Hau
Pranav Gandhi
Mark Lamotte
Publication date
01-12-2019
Publisher
Springer Healthcare
Published in
Diabetes Therapy / Issue 6/2019
Print ISSN: 1869-6953
Electronic ISSN: 1869-6961
DOI
https://doi.org/10.1007/s13300-019-00701-3

Other articles of this Issue 6/2019

Diabetes Therapy 6/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine