INTRODUCTION: Few patients with type 2 diabetes mellitus (T2DM) achieve recommended glycemic control targets in the Czech Republic. Novel therapies, such as fixed-ratio combinations of basal insulin plus glucagon-like peptide-1 receptor agonists, may contribute to better glycemic control. In the analysis presented here, the present analysis assessed the long-term cost-effectiveness of two fixed-ratio combinations, IDegLira (insulin degludec/liraglutide) and iGlarLixi (insulin glargine/lixisenatide), for the treatment of patients with T2DM inadequately controlled with basal insulin from a healthcare payer perspective in the Czech Republic. METHODS: A cost-effectiveness analysis was performed over patient lifetimes using the IQVIA CORE Diabetes Model. Treatment effects were obtained from an indirect treatment comparison as no head-to-head data for IDegLira versus iGlarLixi are currently available. IDegLira was compared with two iGlarLixi pens (100 U/mL insulin glargine + 33 μg/mL and 50 μg/mL of lixisenatide, respectively). Direct medical costs associated with pharmaceutical interventions, screening and diabetes-related complications were captured. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: IDegLira was associated with gains in life expectancy of 0.11 years and in quality-adjusted life expectancy of 0.14 quality-adjusted life-years (QALYs) versus iGlarLixi, due to a lower cumulative incidence and delayed onset of diabetes-related complications. IDegLira was also associated with higher projected costs due to higher acquisition costs; however, these were partially offset by cost savings from avoided complications. IDegLira was associated with incremental cost-effectiveness ratios of Czech Koruna (CZK) 695,998 and CZK 348,323 per QALY gained versus iGlarLixi pens containing 33 and 50 μg/mL of lixisenatide, respectively. These ratios were below the commonly used willingness-to-pay threshold of CZK 1,200,000 per QALY gained. CONCLUSION: The present analysis indicated that IDegLira was associated with clinical benefits relative to iGlarLixi over patient lifetimes and was likely to be cost-effective in the treatment of patients with T2DM uncontrolled on basal insulin in the Czech Republic. FUNDING: Novo Nordisk. Plain language summary is available for this article.

Novo Nordisk Pharma Sp z o o Warsaw Poland

Novo Nordisk s r o Prague Czech Republic

Ossian Health Economics and Communications Basel Switzerland

Zobrazit více v PubMed

Hu FB, Satija A, Manson JE. Curbing the diabetes pandemic: the need for global policy solutions. JAMA. 2015;313(23):2319–2320. doi: 10.1001/jama.2015.5287. PubMed DOI PMC

Ústavu zdravotnických informací a statistiky České republiky (Institute of Health Information and Statistics of the Czech Republic [UZIS]). Stručný přehled činnosti oboru diabetologie a endokrinologie za období 2007–2017 (Brief overview of diabetology and endocrinology in the period 2007–2017). 2018. http://www.uzis.cz/system/files/nzis_rep_2018_K01_A004_diabet_endokrin_2017.pdf. Accessed 10 Dec 2018.

United Kingdom Prospective Diabetes Study Group Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)) Lancet. 1998;352(9131):854–865. doi: 10.1016/s0140-6736(98)07037-8. PubMed DOI

Morales J, Merker L. Minimizing hypoglycemia and weight gain with intensive glucose control: potential benefits of a new combination therapy (IDegLira) Adv Ther. 2015;32(5):391–403. doi: 10.1007/s12325-015-0208-2. PubMed DOI PMC

Česká diabetologická společnost (Czech Diabetes Society). Doporučený postup péče o diabetes mellitus 2. typu -2017 + příloha Algoritmus terapie (Treatment guidelines for type 2 diabetes-2017 + treatment algorithm]) 2017. http://www.diab.cz/dokumenty/standard_lecba_dm_typ_II.pdf and http://www.diab.cz/dokumenty/priloha_algoritmus_terapie.pdf. Accessed 10 Dec 2018.

Brož J, Janíčková Žďárská D, Urbanová J, et al. Current level of glycemic control and clinical inertia in subjects using insulin for the treatment of type 1 and type 2 diabetes in the Czech Republic and the Slovak Republic: results of a multinational, multicenter, observational survey (DIAINFORM) Diabetes Ther. 2018;9(5):1897–1906. doi: 10.1007/s13300-018-0485-2. PubMed DOI PMC

Inman TR, Plyushko E, Austin NP, Johnson JL. The role of basal insulin and GLP-1 receptor agonist combination products in the management of type 2 diabetes. Ther Adv Endocrinol Metab. 2018;9(5):151–155. doi: 10.1177/2042018818763698. PubMed DOI PMC

Maiorino MI, Chiodini P, Bellastella G, Capuano A, Esposito K, Giugliano D. Insulin and glucagon-like peptide 1 receptor agonist combination therapy in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes Care. 2017;40(4):614–624. doi: 10.2337/dc16-1957. PubMed DOI

Valentine V, Goldman J, Shubrook JH. Rationale for, initiation and titration of the basal insulin/GLP-1RA fixed-ratio combination products, IDegLira and iGlarLixi, for the management of type 2 diabetes. Diabetes Ther. 2017;8(4):739–752. doi: 10.1007/s13300-017-0287-y. PubMed DOI PMC

Gough SC, Bode B, Woo V, et al. Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes. Lancet Diabetes Endocrinol. 2014;2(11):885–893. doi: 10.1016/S2213-8587(14)70174-3. PubMed DOI

Linjawi S, Bode BW, Chaykin LB, et al. The efficacy of IDegLira (insulin degludec/liraglutide combination) in adults with type 2 diabetes inadequately controlled with a GLP-1 receptor agonist and oral therapy: DUAL III randomized clinical trial. Diabetes Ther. 2017;8(1):101–114. doi: 10.1007/s13300-016-0218-3. PubMed DOI PMC

Rodbard HW, Bode BW, Harris SB, et al. Safety and efficacy of insulin degludec/liraglutide (IDegLira) added to sulphonylurea alone or to sulphonylurea and metformin in insulin-naïve people with Type 2 diabetes: the DUAL IV trial. Diabet Med. 2017;34(2):189–196. doi: 10.1111/dme.13256. PubMed DOI PMC

Buse JB, Vilsbøll T, Thurman J. Contribution of liraglutide in the fixed-ratio combination of insulin degludec and liraglutide (IDegLira) Diabetes Care. 2014;37(11):2926–2933. doi: 10.2337/dc14-0785. PubMed DOI

Billings LK, Doshi A, Gouet D, et al. Efficacy and safety of IDegLira versus basal-bolus insulin therapy in patients with type 2 diabetes uncontrolled on metformin and basal insulin: the DUAL VII randomized clinical trial. Diabetes Care. 2018;41(5):1009–1016. doi: 10.2337/dc17-1114. PubMed DOI

King AB, Philis-Tsimikas A, Kilpatrick ES, Langbakke IH, Begtrup K, Vilsbøll T. A fixed ratio combination of insulin degludec and liraglutide (IDegLira) reduces glycemic fluctuation and brings more patients with type 2 diabetes within blood glucose target ranges. Diabetes Technol Ther. 2017;19(4):255–264. doi: 10.1089/dia.2016.0405. PubMed DOI PMC

Aroda VR, Rosenstock J, Wysham C, et al. Efficacy and safety of LixiLan, a titratable fixed-ratio combination of insulin glargine plus lixisenatide in type 2 diabetes inadequately controlled on basal insulin and metformin: the LixiLan-L randomized trial. Diabetes Care. 2016;39(11):1972–1980. doi: 10.2337/dc16-1495. PubMed DOI

Rosenstock J, Aronson R, Grunberger G, et al. Benefits of LixiLan, a titratable fixed-ratio combination of insulin glargine plus lixisenatide, versus insulin glargine and lixisenatide monocomponents in type 2 diabetes inadequately controlled on oral agents: the LixiLan-O randomized trial. Diabetes Care. 2016;39(11):2026–2035. doi: 10.2337/dc16-0917. PubMed DOI

Weinstein MC, Stason WB. Foundations of cost-effectiveness analysis for health and medical practices. N Engl J Med. 1977;296(13):716–721. doi: 10.1056/NEJM197703312961304. PubMed DOI

Detsky AS, Naglie IG. A clinician’s guide to cost-effectiveness analysis. Ann Intern Med. 1990;113(2):147–154. doi: 10.7326/0003-4819-113-2-147. PubMed DOI

Kvapil M, Prázný M, Holik P, Rychna K, Hunt B. Cost-effectiveness of IDegLira versus insulin intensification regimens for the treatment of adults with type 2 diabetes in the Czech Republic. Diabetes Ther. 2017;8(6):1331–1347. doi: 10.1007/s13300-017-0323-y. PubMed DOI PMC

Státní stav pro kontrolu léčiv (State Institute for Drug Control). Postup pro posuzování analýzy nákladové efektivity (Guidelines for cost-effectiveness analysis). 2017. https://www.sukl.cz/file/85788_1_1. Accessed 10 Dec 2018.

International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Pharmacoeconomic guidelines around the world—country/region: Czech Republic. 2018. https://tools.ispor.org/PEguidelines/countrydet.asp?c=47&t=2. Accessed 10 Dec 2018.

Marseille E, Larson B, Kazi DS, Kahn JG, Rosen S. Thresholds for the cost-effectiveness of interventions: alternative approaches. Bull World Health Organ. 2015;93(2):118–124. doi: 10.2471/BLT.14.138206. PubMed DOI PMC

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–S26. doi: 10.1185/030079904X1980. PubMed DOI

Palmer AJ, Roze S, Valentine WJ, et al. Validation of the CORE Diabetes Model against epidemiological and clinical studies. Curr Med Res Opin. 2004;20(Suppl 1):S27–S40. doi: 10.1185/030079904X2006. PubMed DOI

McEwan P, Foos V, Palmer JL, Lamotte M, Lloyd A, Grant D. Validation of the IMS CORE diabetes model. Value Health. 2014;17(6):714–724. doi: 10.1016/j.jval.2014.07.007. PubMed DOI

American Diabetes Association Consensus Panel. Guidelines for computer modeling of diabetes and its complications: guidelines for computer modeling of diabetes and its complications. Diabetes Care. 2004;27(9):2262–25. 10.2337/diacare.27.9.2262. PubMed

World Health Organization. Global Health Observatory (GHO) data: life tables by country: Czechia. 2017. http://apps.who.int/gho/data/view.main.60430?lang=en. Accessed 10 Nov 2018.

Attema AE, Brouwer WBF, Claxton K. Discounting in economic evaluations. Pharmacoeconomics. 2018;36(7):745–758. doi: 10.1007/s40273-018-0672-z. PubMed DOI PMC

American Cancer Society, Inc. and Vital Strategies. The tobacco atlas. Czech Republic. 2018. https://tobaccoatlas.org/country/czech-republic/. Accessed 10 Dec 2018.

World Health Organization. Substance abuse: Czech Republic. 2014. http://www.who.int/substance_abuse/publications/global_alcohol_report/profiles/cze.pdf. Accessed 10 Dec 2018.

Evans M, Billings LK, Håkan-Bloch J, et al. An indirect treatment comparison of the efficacy of insulin degludec/liraglutide (IDegLira) and insulin glargine/lixisenatide (iGlarLixi) in patients with type 2 diabetes uncontrolled on basal insulin. J Med Econ. 2018;21(4):340–347. doi: 10.1080/13696998.2017.1409228. PubMed DOI

Jansen JP, Fleurence R, Devine B, et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 1. Value Health. 2011;14(4):417–428. doi: 10.1016/j.jval.2011.04.002. PubMed DOI

Hoaglin DC, Hawkins N, Jansen JP, et al. Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2. Value Health. 2011;14(4):429–437. doi: 10.1016/j.jval.2011.01.011. PubMed DOI

Státní stav pro kontrolu léčiv (State Institute for Drug Control): Medicinal Products Database. 2018. http://www.sukl.eu/modules/medication/search.php. Accessed 10 Dec 2018.

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):462–470. doi: 10.1016/j.jval.2014.03.003. PubMed DOI

Evans M, Khunti K, Mamdani M, et al. 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;11:90. doi: 10.1186/1477-7525-11-90. PubMed DOI PMC

Bagust A, Beale S. Modelling EuroQol health-related utility values for diabetic complications from CODE-2 data. Health Econ. 2005;14(3):217–230. doi: 10.1002/hec.910. PubMed DOI

Wasserfallen JB, Halabi G, Saudan P, et al. Quality of life on chronic dialysis: comparison between haemodialysis and peritoneal dialysis. Nephrol Dial Transplant. 2004;19(6):1594–1599. doi: 10.1093/ndt/gfh175. PubMed DOI

Briggs AH, Weinstein MC, Fenwick EA, et al. Model parameter estimation and uncertainty: a report of the ISPOR-SMDM modeling good research practices task force—6. Value Health. 2012;15(6):835–842. doi: 10.1016/j.jval.2012.04.014. PubMed DOI

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):1523–1534. doi: 10.1185/030079906X115757. PubMed DOI

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):1482–1486. doi: 10.1111/j.1464-5491.2005.01657.x. PubMed DOI

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):2645–2650. doi: 10.1007/s11136-014-0712-x. PubMed DOI

Davies MJ, Glah D, Chubb B, Konidaris G, McEwan P. Cost effectiveness of IDegLira vs. alternative basal insulin intensification therapies in patients with type 2 diabetes mellitus uncontrolled on basal insulin in a UK setting. Pharmacoeconomics. 2016;34(9):953–966. doi: 10.1007/s40273-016-0433-9. PubMed DOI

Hunt B, Glah D, van der Vliet M. Modeling the long-term cost-effectiveness of IDegLira in patients with type 2 diabetes who are failing to meet glycemic targets on basal insulin alone in the Netherlands. Diabetes Ther. 2017;8(4):753–765. doi: 10.1007/s13300-017-0266-3. PubMed DOI PMC

Ericsson Å, Lundqvist A. Cost effectiveness of insulin degludec plus liraglutide (IDegLira) in a fixed combination for uncontrolled type 2 diabetes mellitus in Sweden. Appl Health Econ Health Policy. 2017;15(2):237–248. doi: 10.1007/s40258-016-0301-y. PubMed DOI PMC

Psota M, Psenkova MB, Racekova N, de Arellano RA, Vandebrouck T, Hunt B. Cost-effectiveness analysis of IDegLira versus basal-bolus insulin for patients with type 2 diabetes in the Slovak health system. Clin Outcomes Res. 2017;9:749–762. doi: 10.2147/ceor.s143127. PubMed DOI PMC

Drummond R, Malkin S, Du Preez M, Lee XY, Hunt B. The management of type 2 diabetes with fixed-ratio combination insulin degludec/liraglutide (IDegLira) versus basal-bolus therapy (insulin glargine U100 plus insulin aspart): a short-term cost-effectiveness analysis in the UK setting. Diabetes Obes Metab. 2018;20(10):2371–2378. doi: 10.1111/dom.13375. PubMed DOI PMC

Dias S, Welton NJ, Sutton AJ, Ades AE. Introduction to evidence synthesis for decision making: NICE DSU Technical Support Document No. 1. 2012. National Institute for Health and Care Excellence (NICE): NICE Decision Support Unit Technical Support Documents. 2018. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0089906/. Accessed 10 Dec 2018.

Shinkins B, Yang Y, Abel L, Fanshawe TR. Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological review of health technology assessments. BMC Med Res Methodol. 2017;17(1):56. doi: 10.1186/s12874-017-0331-7. PubMed DOI PMC

Price H, Blüher M, Prager R, Phan TM, Thorsted BL, Schultes B. Use and effectiveness of a fixed-ratio combination of insulin degludec/liraglutide (IDegLira) in a real-world population with type 2 diabetes: results from a European, multicentre, retrospective chart review study. Diabetes Obes Metab. 2018;20(4):954–962. doi: 10.1111/dom.13182. PubMed DOI PMC

Sofra D. Glycemic control in a real-life setting in patients with type 2 diabetes treated with IDegLira at a single Swiss Center. Diabetes Ther. 2017;8(2):377–384. doi: 10.1007/s13300-017-0234-y. PubMed DOI PMC

Drummond R, Baru A, Dutkiewicz M, Basse A, Tengmark BO. Physicians’ real-world experience with IDegLira: results of a European survey. BMJ Open Diabetes Res Care. 2018;6(1):e000531. doi: 10.1136/bmjdrc-2018-000531. PubMed DOI PMC

Russell-Jones D, Pouwer F, Khunti K. Identification of barriers to insulin therapy and approaches to overcoming them. Diabetes Obes Metab. 2018;20(3):488–496. doi: 10.1111/dom.13132. PubMed DOI PMC

Burden of HPV-induced diseases and cost effectiveness of catch-up vaccination in Czech Republic: a model-based study