Cost–effectiveness of empagliflozin compared with liraglutide based on cardiovascular outcome trials in Type II diabetes
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: Cost–effectiveness (CE) analysis of empagliflozin+standard of care (SoC) compared with SoC and liraglutide+SoC, in patients with Type II diabetes and established cardiovascular disease, was conducted using evidence from cardiovascular outcomes trials. Methods: The IQVIA Core Diabetes Model was calibrated to predict same outcomes observed in EMPA-REG OUTCOME and LEADER trials. Three-year observed cardiovascular events of SoC, empagliflozin+SoC and liraglutide+SoC were derived from EMPA-REG OUTCOME trial and an indirect comparison. Time horizon was 50 years and the UK payer perspective was taken. Results: Empagliflozin+SoC dominated liraglutide+SoC with greater quality-adjusted life years and reduced costs. Base-case incremental CE ratio of 6428 GBP/QALY was observed for empagliflozin+SoC versus SoC. Conclusion: Results suggest that empagliflozin+SoC is cost effective versus SoC and liraglutide+SoC.
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References
Papers of special note have been highlighted as: • of interest
1.
International Diabetes Federation. IDF Diabetes Atlas, 9th Edition 2019 (2019). www.diabetesatlas.org/en/
2.
Emerging Risk Factors Collaboration, Sarwar N, Gao P, Kondapally Seshasai SR et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375(9733), 2215–2222 (2010).
3.
Kondapally Seshasai SR, Kaptoge S, Thompson A et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N. Engl. J. Med. 364(9), 829–841 (2011).
4.
Kaul S, Bolger AF, Herrington D, Giugliano RP, Eckel RH. Thiazolidinedione drugs and cardiovascular risks. Circulation 121(16), 1868–1877 (2010).
5.
Food and Drug Administration. Guidance for Industry on Diabetes Mellitus – Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type II Diabetes (2008). www.federalregister.gov/documents/2008/12/19/E8-30086/guidance-for-industry-on-diabetes-mellitus-evaluating-cardiovascular-risk-in-new-antidiabetic
• Sets the need to evaluate diabetes therapies not only from the point of view of controlling blood glucose level, but also demands that industry provides safety data in terms of cardiovascular outcomes (CVO) on drugs. Since then, CVO trials have been designed and run to respond to both needs, in some of them including also other outcomes (e.g., renal outcomes).
6.
European Medicines Agency. Guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus (2012). www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-investigation-medicinal-products-treatment-prevention-diabetes-mellitus-revision_en.pdf
• Sets the need to evaluate diabetes therapies not only from the point of view of controlling blood glucose level, but also demands that industry provides safety data in terms of CVO on drugs. Since then, CVO trials have been designed and run to respond to both needs, in some of them including also other outcomes (e.g., renal outcomes).
7.
Scirica BM, Bhatt DL, Braunwald E et al. Saxagliptin and cardiovascular outcomes in patients with Type II diabetes mellitus. N. Engl. J. Med. 369(14), 1317–1326 (2013).
8.
White WB, Cannon CP, Heller SR et al. Alogliptin after acute coronary syndrome in patients with Type II diabetes. N. Engl. J. Med. 369(14), 1327–1335 (2013).
9.
Green JB, Bethel MA, Armstrong PW et al. Effect of sitagliptin on cardiovascular outcomes in Type II diabetes. N. Engl. J. Med. 373(3), 232–242 (2015).
10.
Pfeffer MA, Claggett B, Diaz R et al. Lixisenatide in patients with Type II diabetes and acute coronary syndrome. N. Engl. J. Med. 373(23), 2247–2257 (2015).
11.
Marso SP, Daniels GH, Brown-Frandsen K et al. Liraglutide and cardiovascular outcomes in Type II diabetes. N. Engl. J. Med. 375(4), 311–322 (2016).
• Describes the efficacy of liraglutide versus standard of care that allowed to estimate the clinical outcomes in the liraglutide arm.
12.
Marso SP, Bain SC, Consoli A et al. Semaglutide and cardiovascular outcomes in patients with Type II diabetes. N. Engl. J. Med. 375(19), 1834–1844 (2016).
13.
Holman RR, Bethel MA, Mentz RJ et al. Effects of once-weekly exenatide on cardiovascular outcomes in Type II diabetes. N. Engl. J. Med. 377(13), 1228–1239 (2017).
14.
Zinman B, Wanner C, Lachin JM et al. Empagliflozin, cardiovascular outcomes, and mortality in Type II diabetes. N. Engl. J. Med. 373(22), 2117–2128 (2015).
• Describes the efficacy of empagliflozin versus standard of care in terms of changes in physiological parameters and CVD and renal outcomes.
15.
Neal B, Perkovic V, Mahaffey KW et al. Canagliflozin and cardiovascular and renal events in Type II diabetes. N. Engl. J. Med. 377(7), 644–657 (2017).
16.
Nathan DM, Buse JB, Davidson MB et al. Medical management of hyperglycemia in Type II diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 32(1), 193–203 (2009).
17.
on behalf of the D&CVD EASD Study Group. Schnell O, Rydén L, Standl E, Ceriello A. Current perspectives on cardiovascular outcome trials in diabetes. Cardiovasc. Diabetol. 15(1), 139 (2016).
18.
Mudaliar S, Alloju S, Henry RR. Can a shift in fuel energetics explain the beneficial cardiorenal outcomes in the EMPA-REG OUTCOME Study? A unifying hypothesis. Diabetes Care 39(7), 1115–1122 (2016).
19.
Abdul-Ghani M, DeFronzo RA, Del Prato S, Chilton R, Singh R, Ryder REJ. Cardiovascular disease and Type II diabetes: has the dawn of a new era arrived? Diabetes Care 40(7), 813–820 (2017).
20.
Ferrannini E, Mark M, Mayoux E. CV protection in the EMPA-REG OUTCOME Trial: a “thrifty substrate” hypothesis. Diabetes Care 39(7), 1108–1114 (2016).
21.
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. 20(Suppl. 1), S5–S26 (2004).
• Along with reference 22, one of the standard articles to describe the IQVIA Core Diabetes model, its structure and functionality and validation.
22.
McEwan P, Foos V, Palmer JL, Lamotte M, Lloyd A, Grant D. Validation of the IMS CORE diabetes model. Value Health 17(6), 714–724 (2014).
• Along with reference 21, one of the standard articles to describe the IQVIA Core Diabetes model, its structure and functionality and validation.
23.
Ramos M, Foos V, Ustyugova A, Hau N, Gandhi P, Lamotte M. Cost–effectiveness analysis of empagliflozin in comparison to sitagliptin and saxagliptin based on cardiovascular outcome trials in patients with Type II diabetes and established cardiovascular disease. Diabetes Ther. 10(6), 2153–2167 (2019).
24.
Clarke PM, Gray AM, Briggs A et al. A model to estimate the lifetime health outcomes of patients with Type II diabetes: the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model (UKPDS no. 68). Diabetologia 47(10), 1747–1759 (2004).
25.
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 II diabetes mellitus using data from the 30 year United Kingdom Prospective Diabetes Study: UKPDS 82. Diabetologia 56(9), 1925–1933 (2013).
26.
Kengne AP, Patel A, Marre M et al. Contemporary model for cardiovascular risk prediction in people with Type II diabetes. Eur. J. Cardiovasc. Prev. Rehabil. 18(3), 393–398 (2011).
27.
Ahmad Kiadaliri A, Clarke PM, Gerdtham U-G et al. Predicting changes in cardiovascular risk factors in Type II diabetes in the post-UKPDS era: longitudinal analysis of the Swedish National Diabetes Register. J. Diabetes Res. 2013, 241347 (2013).
28.
Cederholm J, Eeg-Olofsson K, Eliasson B, Zethelius B, Nilsson PM, Gudbjörnsdottir S. Risk prediction of cardiovascular disease in Type II diabetes. Diabetes Care 31(10), 2038–2043 (2008).
29.
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 26(10), 2777–2784 (2003).
30.
Davis WA, Knuiman MW, Davis TME. An Australian cardiovascular risk equation for Type II diabetes: the Fremantle Diabetes Study. Intern. Med. J. 40(4), 286–292 (2010).
31.
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 105(3), 310–315 (2002).
32.
Balijepalli C, Ayers D, Kandaswamy P et al. Cardiovascular safety of empagliflozin versus glucagon-like peptide-1 (GLP-1) receptor agonists: systematic literature review and indirect comparisons (Abstract). Presented at: ISPOR Europe, Barcelona, Spain (2018).
33.
Wanner C, Inzucchi SE, Lachin JM et al. Empagliflozin and progression of kidney disease in Type II diabetes. N. Engl. J. Med. 375(4), 323–334 (2016).
• Describes the efficacy of empagliflozin versus standard of care in terms of changes in physiological parameters and CVD and renal outcomes.
34.
Database of prescription and generic drugs, clinical guidelines. MIMS online (2019). www.mims.co.uk/
35.
Personal Social Services Research Unit. Unit Costs of Health and Social Care 2017 (2017). www.pssru.ac.uk/project-pages/unit-costs/unit-costs-2017/
36.
Riddle MC, Bolli GB, Ziemen M et al. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with Type II diabetes using basal and mealtime insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 1). Diabetes Care 37(10), 2755–2762 (2014).
37.
BNF Publications. BNF Online (2020). www.bnf.org/products/bnf-online/
38.
Beaudet A, Clegg J, Thuresson P-O, Lloyd A, McEwan P. Review of utility values for economic modeling in Type II diabetes. Value Health 17(4), 462–470 (2014).
39.
Bagust A, Beale S. Modelling EuroQol health-related utility values for diabetic complications from CODE-2 data. Health Econ. 14(3), 217–230 (2005).
40.
NICE. Developing NICE guidelines: the manual (2014). www.nice.org.uk/process/pmg20/chapter/introduction-and-overview
41.
Daacke I, Kandaswamy P, Tebboth A, Kansal A, Reifsnider O. Cost–effectiveness of empagliflozin (Jardiance) in the treatment of patients with Type II diabetes mellitus (T2DM) in the UK based on EMPA-REG OUTCOME data. Value Health 19(7), A673 (2016).
42.
Gourzoulidis G, Tzanetakos C, Ioannidis I et al. Cost–effectiveness of empagliflozin for the treatment of patients with Type II diabetes mellitus at increased cardiovascular risk in Greece. Clin. Drug Investig. 38(5), 417–426 (2018).
43.
Iannazzo S, Mannucci E, Reifsnider O, Maggioni AP. Cost–effectiveness analysis of empagliflozin in the treatment of patients with Type II diabetes and established cardiovascular disease in Italy, based on the results of the EMPA-REG OUTCOME study. Farmeconomia Health Econ. Ther. Pathw. 18(1), (2017).
44.
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 67(Suppl. 1), 1294–P (2018).
45.
Mettam SR, Bajaj H, Kansal AR, Kandaswamy P. Cost–effectiveness of empagliflozin in patients with T2DM and high CV risk in Canada. Value Health 19(7), A674 (2016).
46.
Nguyen E, Coleman CI, Nair S, Weeda ER. Cost-utility of empagliflozin in patients with Type II diabetes at high cardiovascular risk. J. Diabetes Complications 32(2), 210–215 (2018).
47.
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 II diabetes in China. Diabetes 68(Suppl. 1), 1292–P (2019).
48.
Balijepalli C, Shirali R, Kandaswamy P et al. Cardiovascular safety of empagliflozin versus dipeptidyl peptidase-4 (DPP-4) inhibitors in Type II diabetes: systematic literature review and indirect comparisons. Diabetes Ther. 9(4), 1491–1500 (2018).
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PubMed: 32573253
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© 2020 M Ramos, A Ustyugova, N Hau & M Lamotte. This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License
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Received: 6 May 2020
Accepted: 26 May 2020
Published online: 23 June 2020
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Cost–effectiveness of empagliflozin compared with liraglutide based on cardiovascular outcome trials in Type II diabetes. (2020) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2020-0071
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- Gianni Ghetti, Lorenzo Pradelli, Giannis Papageorgiou, George Karpouzos, Yelda Arikan, CELESTIA: Cost-Effectiveness Analysis of Empagliflozin Versus Sitagliptin in Patients with Type 2 Diabetes in Greece, ClinicoEconomics and Outcomes Research, 10.2147/CEOR.S400522, Volume 15, (97-109), (2023).
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- Marc Evans, Sasha Berry, Avideh Nazeri, Samuel JP Malkin, Donna Ashley, Barnaby Hunt, Stephen C Bain, The challenges and pitfalls of incorporating evidence from cardiovascular outcomes trials in health economic modelling of type 2 diabetes, Diabetes, Obesity and Metabolism, 10.1111/dom.14917, 25, 3, (639-648), (2022).
- Odette S. Reifsnider, Pratik Pimple, Sarah Brand, Evelien Bergrath Washington, Sharash Shetty, Nihar R. Desai, Cost‐effectiveness of second‐line empagliflozin versus liraglutide for type 2 diabetes in the United States , Diabetes, Obesity and Metabolism, 10.1111/dom.14625, 24, 4, (652-661), (2022).
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