The Cost-Effectiveness of Oral Semaglutide in Spain: A Long-Term Health Economic Analysis Based on the PIONEER Clinical Trials
Tóm tắt
Novel glucagon-like peptide-1 (GLP-1) receptor agonist oral semaglutide has demonstrated greater improvements in glycated hemoglobin (HbA1c) and body weight versus oral medications empagliflozin and sitagliptin, and injectable GLP-1 analog liraglutide, in the PIONEER clinical trial program. Based on these data, the present analysis aimed to evaluate the long-term cost-effectiveness of oral semaglutide versus empagliflozin, sitagliptin and liraglutide in Spain. Outcomes were projected over patients’ lifetimes using the IQVIA CORE Diabetes Model (v9.0), discounted at 3.0% annually. Cohort characteristics and treatment effects were sourced from PIONEER 2 and 4 for the comparisons of oral semaglutide 14 mg versus empagliflozin 25 mg and liraglutide 1.8 mg, respectively, and PIONEER 3 for oral semaglutide 7 and 14 mg versus sitagliptin 100 mg. Costs were accounted from a healthcare payer perspective in 2020 euros (EUR). Patients were assumed to receive initial therapies until HbA1c exceeded 7.5% and then treatment-intensified to basal insulin. Oral semaglutide 14 mg was associated with improvements in quality-adjusted life expectancy of 0.13, 0.19 and 0.06 quality-adjusted life years (QALYs) versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg, respectively, with direct costs EUR 168 higher versus empagliflozin and EUR 236 and 1415 lower versus sitagliptin and liraglutide, respectively. Oral semaglutide 14 mg was associated with an incremental cost-effectiveness ratio (ICER) of EUR 1339 per QALY gained versus empagliflozin and was considered dominant (clinically superior and cost saving) versus sitagliptin and liraglutide. Additional analyses demonstrated that oral semaglutide 7 mg was associated with improvements of 0.11 QALYs and increased costs of EUR 226 versus sitagliptin and was therefore associated with an ICER of EUR 2011 per QALY gained. Oral semaglutide 14 mg was dominant versus sitagliptin and liraglutide, and cost-effective versus empagliflozin, for the treatment of type 2 diabetes in Spain.
Tài liệu tham khảo
International Diabetes Federation (IDF). Diabetes Atlas—10th Edition. 2021. Available at: https://diabetesatlas.org/data/en/country/209/gb.html [Last accessed December 10, 2021].
Soriguer F, Goday A, Bosch-Comas A, Bordiú E, Calle-Pascual A, Carmena R, et al. Prevalence of diabetes mellitus and impaired glucose regulation in Spain: the [email protected] Study. Diabetologia. 2012;55(1):88–93
Rojo-Martínez G, Valdés S, Soriguer F, et al. Incidence of diabetes mellitus in Spain as results of the nation-wide cohort [email protected] study. Sci Rep. 2020;10:2765.
Lopez-Bastida J, Boronat M, Moreno JO, et al. Costs, outcomes and challenges for diabetes care in Spain. Global Health. 2013;9:17.
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577–89.
Stettler C, Allemann S, Jüni P, Cull CA, Holman RR, Egger M, et al. Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: Meta-analysis of randomized trials. Am Heart J. 2006;152:27–38.
Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet. 2010;376:419–30.
ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J, Neal B, Billot L, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560–72.
Mata-Cases M, Rodríguez-Sánchez B, Mauricio D, et al. The association between poor glycemic control and health care costs in people with diabetes: a population-based study. Diabetes Care. 2020;43(4):751–8.
Mata-Cases M, Mahon J, Mauricio D, et al. Improving management of glycaemic control in people with T2DM in primary care: estimation of the impact on the clinical complications and associated costs. BMC Health Serv Res. 2020;20:803.
Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358:580–91.
Cholesterol Treatment Trialists' (CTT) Collaborators, Kearney PM, Blackwell L, Collins R, Keech A, Simes J, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008;371:117–25.
UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317:703–13.
Gomez-Peralta F, Escalada San Martín FJ, Menéndez Torre E, et al. Recomendaciones de la Sociedad Española de Diabetes (SED) para el tratamiento farmacológico de la hiperglucemia en la diabetes tipo 2: Actualización 2018. Endocrinol Diabetes Nutr. 2018;65:611–24.
European Medicines Agency (EMA). Human Medicines Highlights 2020. 2020. Available at: https://www.ema.europa.eu/en/documents/report/human-medicines-highlights-2020_en.pdf [Last accessed December 15, 2021].
Rodbard HW, Rosenstock J, Canani LH, Deerochanawong C, Gumprecht J, Lindberg SØ, et al. Oral semaglutide versus empagliflozin in patients with type 2 diabetes uncontrolled on metformin: The PIONEER 2 trial. Diabetes Care. 2019;42:2272–81.
Rosenstock J, Allison D, Birkenfeld AL, Blicher TM, Deenadayalan S, Jacobsen JB, et al. Effect of additional oral semaglutide vs sitagliptin on glycated hemoglobin in adults with type 2 diabetes uncontrolled with metformin alone or with sulfonylurea: the PIONEER 3 randomized clinical trial. JAMA. 2019;321:1466–80.
Pratley R, Amod A, Hoff ST, Kadowaki T, Lingvay I, Nauck M, et al. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet. 2019;394:39–50.
Bain SC, Hansen BB, Malkin SJP, Nuhoho S, Valentine WJ, Chubb B, Hunt B, Capehorn M. Oral Semaglutide Versus Empagliflozin, Sitagliptin and Liraglutide in the UK: long-term cost-effectiveness analyses based on the pioneer clinical trial programme. Diabetes Ther. 2020;11(1):259–77.
Malkin SJP, Hunt B, Huisman EL, Grand TS, Chubb B. The long-term cost-effectiveness of oral semaglutide in the Netherlands based on the PIONEER 2, 3 and 4 randomized controlled trials. Diabetes Res Clin Pract. 2021;175:108759.
European Medicines Agency. Press release: First oral GLP-1 treatment for type 2 diabetes. 2020. Available at: https://www.ema.europa.eu/en/news/first-oral-glp-1-treatment-type-2-diabetes [Last accessed November 5, 2021].
American Diabetes Association Consensus Panel. Guidelines for computer modeling of diabetes and its complications. Diabetes Care. 2004;27:2262–5.
Palmer AJ, Roze S, Valentine WJ, Minshall ME, Foos V, Lurati FM, 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.
Palmer AJ, Roze S, Valentine WJ, Minshall ME, Foos V, Lurati FM, Let al. Validation of the CORE Diabetes Model against epidemiological and clinical studies. Curr Med Res Opin 2004;20(Suppl 1):S27–40.
McEwan P, Foos V, Palmer JL, Lamotte M, Lloyd A, Grant D. Validation of the IMS CORE diabetes model. Value Health. 2014;17:714–24.
Lopez Bastida J, Oliva J, Antonanzas F, Garcia-Altes A, Gisbert R, Mar J, Puig-Junoy J. A proposed guideline for economic evaluation of health technologies. Gac Sanit. 2010;24(2):154–70.
World Health Organisation. Global Health Observatory data repository: Life tables by country (Spain). 2020. Available at: https://apps.who.int/gho/data/view.main.LT62210?lang=en [Last accessed November 5, 2021].
Briggs AH, Weinstein MC, Fenwick EA Karnon J, Sculpher MJ, Paltiel AD, et al. Model parameter estimation and uncertainty: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force--6. Value Health 2012;15:835–42.
Aroda VR, Saugstrup T, Buse JB, Donsmark M, Zacho J, Davies MJ. Incorporating and interpreting regulatory guidance on estimands in diabetes clinical trials: the PIONEER 1 randomized clinical trial as an example. Diabetes Obes Metab. 2019;21:2203–10.
Reyes-García R, Moreno-Pérez Ó, Tejera-Pérez C, et al. Document on a comprehensive approach to type 2 diabetes mellitus. Endocrinol Diabetes Nutr (Engl Ed). 2019;66(7):443–58.
Willis M, Asseburg C, Nilsson A, Johnsson K, Kartman B. Multivariate prediction equations for HbA1c lowering, weight change, and hypoglycemic events associated with insulin rescue medication in type 2 diabetes mellitus: Informing economic modeling. Value Health. 2017;20:357–71.
Russell-Jones D, Khan R. Insulin-associated weight gain in diabetes–causes, effects and coping strategies. Diabetes Obes Metab. 2007;9(6):799–812.
UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia. 2007;50:1140–7.
Gorgojo-Martínez JJ, Malkin SJP, Martín V, Hallén N, Hunt B. Assessing the cost-effectiveness of a once-weekly GLP-1 analogue versus an SGLT-2 inhibitor in the Spanish setting: once-weekly semaglutide versus empagliflozin. J Med Econ. 2020;23(2):193–202.
Martín V, Vidal J, Malkin SJP, Hallén N, Hunt B. Evaluation of the long-term cost-effectiveness of once-weekly semaglutide versus dulaglutide and sitagliptin in the spanish setting. Adv Ther. 2020;37(10):4427–45.
Instituto Nacional de Estadística [National Institute of Statistics]. Índices nacionales: general y de grupos ECOICOP [National indices: general and ECOICOP groups]. 2021. Available at: https://www.ine.es/jaxiT3/Datos.htm?t=22344#!tabs-tabla [Last accessed November 1, 2021].
Beaudet A, Clegg J, Thuresson PO, Lloyd A, McEwan P. Review of utility values for economic modeling in type 2 diabetes. Value Health. 2014;17(4):462–70.
Evans M, Khunti K, Mamdani M, Galbo-Jorgensen CB, Gundgaard J, Bogelund M, Harris S. Health-related quality of life associated with daytime and nocturnal hypoglycaemic events: a time trade-off survey in five countries. Health Qual Life Outcomes. 2013;11(1):90.
Lee AJ, Morgan CL, Morrissey M, Wittrup-Jensen KU, Kennedy-Martin T, Currie CJ. Evaluation of the association between the EQ-5D (health-related utility) and body mass index (obesity) in hospital-treated people with Type 1 diabetes, Type 2 diabetes and with no diagnosed diabetes. Diabet Med. 2005;22(11):1482–6.
Lauridsen JT, Lønborg J, Gundgaard J, Jensen HH. Diminishing marginal disutility of hypoglycaemic events: results from a time trade-off survey in five countries. Qual Life Res. 2014;23(9):2645–50.
Currie CJ, Morgan CL, Poole CD, Sharplin P, Lammert M, McEwan P. Multivariate models of health-related utility and the fear of hypoglycaemia in people with diabetes. Curr Med Res Opin. 2006;22(8):1523–34.
Sacristán JA, Oliva J, Del Llano J, Prieto L, Pinto JL. Qué es una tecnología sanitaria eficiente en España? [What is an efficient health technology in Spain?]. Gac Sanit. 2002;16(4):334–43.
Khunti K, Wolden ML, Thorsted BL, Andersen M, Davies MJ. Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people. Diabetes Care. 2013;36:3411–7.
Husain M, Bain SC, Jeppesen OK, Lingvay I, Sørrig R, Treppendahl MB, et al. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020;22:442–51.
Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S et al. (EMPA-REG OUTCOME Investigators). Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117–28.
Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA et al. (LEADER Trial Investigators). Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375:311–22.
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.
Buse JB, Wexler DJ, Tsapas A, et al. 2019 Update to: 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. 2019; dci190066.
Si L, Willis MS, Asseburg C, et al. Evaluating the ability of economic models of diabetes to simulate new cardiovascular outcomes trials: a report on the ninth mount hood diabetes challenge. Value Health. 2020;23(9):1163–70.
Willis M, Asseburg C, Nilsson A, Neslusan C. Challenges and opportunities associated with incorporating new evidence of drug-mediated cardioprotection in the economic modeling of type 2 diabetes: a literature review. Diabetes Ther. 2019;10:1753–69.