Long-term Cost-effectiveness of Insulin Degludec Versus Insulin Glargine U100 in the UK: Evidence from the Basal-bolus Subgroup of the DEVOTE Trial (DEVOTE 16)

Richard F Pollock, William J Valentine, Steven P Marso, Andreas Andersen, Jens Gundgaard, Nino Hallén, Deniz Tutkunkardas, Elizabeth A Magnuson, John B Buse, DEVOTE study group, Richard F Pollock, William J Valentine, Steven P Marso, Andreas Andersen, Jens Gundgaard, Nino Hallén, Deniz Tutkunkardas, Elizabeth A Magnuson, John B Buse, DEVOTE study group

Abstract

Objectives: To evaluate the cost-effectiveness of insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) in basal-bolus regimens for patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk based on the DEVOTE CV outcomes trial.

Methods: A microsimulation model, informed by clinical outcomes from the subgroup of patients using basal-bolus insulin therapy in DEVOTE (NCT01959529) and by the UKPDS Outcomes Model 2 risk equations, was used to model direct costs (2018 GBP) and effectiveness outcomes [quality-adjusted life years (QALYs)] with degludec versus glargine U100 over a 40-year time horizon. The model captured the development of eight diabetes-related complications, death, severe hypoglycemia and insulin dosing. This analysis was conducted from the perspective of National Health Service (NHS) England.

Results: Treatment with degludec versus glargine U100 in basal-bolus regimens was associated with improved clinical outcomes at a higher cost per patient [incremental cost effectiveness ratio (ICER): £14,956 GBP/QALY]. Degludec remained cost effective versus glargine U100 in all exploratory sensitivity analyses, with ICERs below the widely accepted willingness-to-pay threshold, although the result was most sensitive to assumptions regarding the persistence of treatment effects.

Conclusions: Our long-term modeling analysis suggested that degludec was cost effective (from the perspective of NHS England) versus glargine U100 in basal-bolus regimens for patients with T2D at high CV risk. Our findings raise important questions regarding how to model the health economics of diabetes therapies.

Figures

Fig. 1
Fig. 1
Results of the probabilistic sensitivity analysis. a Cost-effectiveness scatterplot. b Cost-effectiveness acceptability curve. For a, the majority of points located in the upper right-hand quadrant of the plot indicates higher costs and improved effectiveness for degludec versus glargine U100. GBP pounds sterling, QALY quality-adjusted life year

References

    1. International Diabetes Federation. IDF Diabetes Atlas, 8th edn. 2017. . Accessed June 2019.
    1. Kanavos P, Van den Aardweg S, Schurer W. Diabetes expenditure, burden of disease and management in 5 EU countries. London: London School of Economics; 2012.
    1. Hex N, Bartlett C, Wright D, Taylor M, Varley D. Estimating the current and future costs of type 1 and type 2 diabetes in the UK, including direct health costs and indirect societal and productivity costs. Diabet Med. 2012;29(7):855–862. doi: 10.1111/j.1464-5491.2012.03698.x.
    1. Caro JJ, Briggs AH, Siebert U, Kuntz KM. Modeling good research practices–overview: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force-1. Value Health J Int Soc Pharmacoecon Outcomes Res. 2012;15(6):796–803. doi: 10.1016/j.jval.2012.06.012.
    1. Palmer AJ, Si L, Tew M, Hua X, Willis MS, Asseburg C, et al. Computer modeling of diabetes and its transparency: a report on the eighth mount hood challenge. Value health J Int Soc Pharmacoecon Outcomes Res. 2018;21(6):724–731. doi: 10.1016/j.jval.2018.02.002.
    1. Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, Lafont S, Bergeonneau C, Kassai B, et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ. 2011;343:d4169. doi: 10.1136/bmj.d4169.
    1. Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375(9733):2215–2222. doi: 10.1016/S0140-6736(10)60484-9.
    1. Gregg EW, Gu Q, Cheng YJ, Narayan KM, Cowie CC. Mortality trends in men and women with diabetes, 1971 to 2000. Ann Intern Med. 2007;147(3):149–155. doi: 10.7326/0003-4819-147-3-200708070-00167.
    1. Schnell O, Ryden L, Standl E, Ceriello A. Updates on cardiovascular outcome trials in diabetes. Cardiovasc Diabetol. 2017;16(1):128. doi: 10.1186/s12933-017-0610-y.
    1. Schnell O, Ryden L, Standl E, Ceriello A. Current perspectives on cardiovascular outcome trials in diabetes. Cardiovasc Diabetol. 2016;15(1):139. doi: 10.1186/s12933-016-0456-8.
    1. Marso SP, McGuire DK, Zinman B, Poulter NR, Emerson SS, Pieber TR, et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med. 2017;377(8):723–732. doi: 10.1056/NEJMoa1615692.
    1. Ericsson A, Pollock RF, Hunt B, Valentine WJ. Evaluation of the cost-utility of insulin degludec vs insulin glargine in Sweden. J Med Econ. 2013;16(12):1442–1452. doi: 10.3111/13696998.2013.852099.
    1. Evans M, Wolden M, Gundgaard J, Chubb B, Christensen T. Cost-effectiveness of insulin degludec compared with insulin glargine for patients with type 2 diabetes treated with basal insulin—from the UK health care cost perspective. Diabetes Obes Metab. 2014;16(4):366–375. doi: 10.1111/dom.12250.
    1. Evans M, Wolden M, Gundgaard J, Chubb B, Christensen T. Cost-effectiveness of insulin degludec compared with insulin glargine in a basal-bolus regimen in patients with type 1 diabetes mellitus in the UK. J Med Econ. 2015;18(1):56–68. doi: 10.3111/13696998.2014.971160.
    1. Evans M, Chubb B, Gundgaard J. Cost-effectiveness of insulin degludec versus insulin glargine in adults with type 1 and type 2 diabetes mellitus. Diabetes Ther. 2017;8(2):275–291. doi: 10.1007/s13300-017-0236-9.
    1. Pollock RF, Tikkanen CK. A short-term cost-utility analysis of insulin degludec versus insulin glargine U100 in patients with type 1 or type 2 diabetes in Denmark. J Med Econ. 2017;20(3):213–220. doi: 10.1080/13696998.2016.1245663.
    1. Mezquita-Raya P, Darba J, Ascanio M, Ramirez de Arellano A. Cost-effectiveness analysis of insulin degludec compared with insulin glargine u100 for the management of type 1 and type 2 diabetes mellitus—from the Spanish National Health System perspective. Expert Rev Pharmacoecon Outcomes Res. 2017;17(6):587–595. doi: 10.1080/14737167.2017.1345628.
    1. Lalic N, Russel-Szymczyk M, Culic M, Tikkanen CK, Chubb B. Cost-effectiveness of insulin degludec versus insulin glargine U100 in patients with type 1 and type 2 diabetes mellitus in serbia. Diabetes Ther Res Treat Educ Diabetes Relat Disord. 2018;9(3):1201–1216. doi: 10.1007/s13300-018-0426-0.
    1. Pollock RF, Valentine WJ, Marso SP, Gundgaard J, Hallen N, Hansen LL, et al. DEVOTE 5: evaluating the short-term cost-utility of insulin degludec versus insulin glargine U100 in basal-bolus regimens for type 2 diabetes in the UK. Diabetes Ther. 2018;9(3):1217–1232. doi: 10.1007/s13300-018-0430-4.
    1. Zoungas S, Woodward M, Li Q, Cooper ME, Hamet P, Harrap S, et al. Impact of age, age at diagnosis and duration of diabetes on the risk of macrovascular and microvascular complications and death in type 2 diabetes. Diabetologia. 2014;57(12):2465–2474. doi: 10.1007/s00125-014-3369-7.
    1. Elliott L, Fidler C, Ditchfield A, Stissing T. Hypoglycemia event rates: a comparison between real-world data and randomized controlled trial populations in insulin-treated diabetes. Diabetes Ther. 2016;7(1):45–60. doi: 10.1007/s13300-016-0157-z.
    1. Marso SP, McGuire DK, Zinman B, Poulter NR, Emerson SS, Pieber TR, et al. Design of DEVOTE (trial comparing cardiovascular safety of insulin degludec vs insulin glargine in patients with type 2 diabetes at high risk of cardiovascular events)—DEVOTE 1. Am Heart J. 2016;179:175–183. doi: 10.1016/j.ahj.2016.06.004.
    1. Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, et al. Hypoglycemia and diabetes: a report of a workgroup of the american diabetes association and the endocrine society. Diabetes Care. 2013;36(5):1384–1395. doi: 10.2337/dc12-2480.
    1. 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):1925–1933. doi: 10.1007/s00125-013-2940-y.
    1. Clarke PM, Gray AM, Briggs A, Farmer AJ, Fenn P, Stevens RJ, et al. A model to estimate the lifetime health outcomes of patients with type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model (UKPDS no. 68) Diabetologia. 2004;47(10):1747–1759. doi: 10.1007/s00125-004-1527-z.
    1. Clarke PM, Simon J, Cull CA, Holman RR. Assessing the impact of visual acuity on quality of life in individuals with type 2 diabetes using the short form-36. Diabetes Care. 2006;29(7):1506–1511. doi: 10.2337/dc05-2150.
    1. Personal Social Services Research Unit. The hospital and community health services index. 2017. . Accessed June 2018.
    1. National Institute for Health and Care Excellence. NICE Process and Methods Guides. Guide to the Methods of Technology Appraisal 2013. 2013. . Accessed Nov 2017.
    1. National Institute for Health and Care Excellence. Process and Methods [PMG20]. Developing NICE guidelines: the manual. 2014. . Accessed Sept 2018.
    1. Cefalu WT, Kaul S, Gerstein HC, Holman RR, Zinman B, Skyler JS, et al. Cardiovascular outcomes trials in type 2 diabetes: where do we go from here? Reflections from a diabetes care editors’ expert forum. Diabetes Care. 2018;41(1):14–31. doi: 10.2337/dci17-0057.
    1. MIMS UK. Monthly index of medical specialities (MIMS). 2018. . Accessed June 2018.
    1. Alva ML, Gray A, Mihaylova B, Leal J, Holman RR. The impact of diabetes-related complications on healthcare costs: new results from the UKPDS (UKPDS 84) Diabet Med. 2015;32(4):459–466. doi: 10.1111/dme.12647.
    1. Improvement NEaN. National tariff values 2017/18. 2017/18. . Accessed June 2018.
    1. UK Renal Registry. 19th Annual Report of the Renal Association. 2016. . Accessed June 2018.
    1. Ghatnekar O, Willis M, Persson U. Cost-effectiveness of treating deep diabetic foot ulcers with Promogran in four European countries. J Wound Care. 2002;11(2):70–74. doi: 10.12968/jowc.2002.11.2.26675.
    1. Hammer M, Lammert M, Mejias SM, Kern W, Frier BM. Costs of managing severe hypoglycaemia in three European countries. J Med Econ. 2009;12(4):281–290. doi: 10.3111/13696990903336597.
    1. Clarke P, Gray A, Holman R. Estimating utility values for health states of type 2 diabetic patients using the EQ-5D (UKPDS 62) Med Decis Mak Int J Soc Med Decis Mak. 2002;22(4):340–349. doi: 10.1177/027298902400448902.
    1. Wasserfallen JB, Halabi G, Saudan P, Perneger T, Feldman HI, Martin PY, 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.
    1. 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.
    1. Evans M, Khunti K, Mamdani M, Galbo-Jorgensen CB, Gundgaard J, Bogelund 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.
    1. Waugh N, Cummins E, Royle P, Clar C, Marien M, Richter B, et al. Newer agents for blood glucose control in type 2 diabetes: systematic review and economic evaluation. Health Technol assessment (Winchester, England) 2010;14(36):1–248. doi: 10.3310/hta14360.
    1. 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.
    1. Hunt B, Ye Q, Valentine WJ, Ashley D. Evaluating the long-term cost-effectiveness of daily administered GLP-1 receptor agonists for the treatment of type 2 diabetes in the United Kingdom. Diabetes Ther. 2017;8(1):129–147. doi: 10.1007/s13300-016-0219-2.
    1. Sullivan PW, Ghushchyan VH. EQ-5D scores for diabetes-related comorbidities. Value Health J Int Soc Pharmacoecon Outcomes Res. 2016;19(8):1002–1008. doi: 10.1016/j.jval.2016.05.018.
    1. 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–S26. doi: 10.1185/030079904X1980.
    1. Hayes A, Arima H, Woodward M, Chalmers J, Poulter N, Hamet P, et al. Changes in quality of life associated with complications of diabetes: results from the ADVANCE study. Value Health J Int Soc Pharmacoecon Outcomes Res. 2016;19(1):36–41. doi: 10.1016/j.jval.2015.10.010.

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