Treating Type 1 Diabetes Mellitus with a Rapid-Acting Analog Insulin Regimen vs. Regular Human Insulin in Germany: A Long-Term Cost-Effectiveness Evaluation
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The aim of the present study was to evaluate the cost effectiveness of rapid-acting analog insulin relative to regular human insulin in adults with type 1 diabetes mellitus in Germany.
The PRIME Diabetes Model, a patient-level, discrete event simulation model, was used to project long-term clinical and cost outcomes for patients with type 1 diabetes from the perspective of a German healthcare payer. Simulated patients had a mean age of 21.5 years, duration of diabetes of 8.6 years, and baseline glycosylated hemoglobin of 7.39%. Regular human insulin and rapid-acting analog insulin regimens reduced glycosylated hemoglobin by 0.312 and 0.402%, respectively. Compared with human insulin, hypoglycemia rate ratios with rapid-acting analog insulin were 0.51 (non-severe nocturnal) and 0.80 (severe). No differences in non-severe diurnal hypoglycemia were modeled. Discount rates of 3% were applied to future costs and clinical benefits accrued over the 50-year time horizon.
In the base-case analysis, rapid-acting analog insulin was associated with an improvement in quality-adjusted life expectancy of 1.01 quality-adjusted life-years per patient (12.54 vs. 11.53 quality-adjusted life-years). Rapid-acting analog insulin was also associated with an increase in direct costs of €4490, resulting in an incremental cost-effectiveness ratio of €4427 per quality-adjusted life-year gained vs. human insulin. Sensitivity analyses showed that the base case was driven predominantly by differences in hypoglycemia; abolishing these differences reduced incremental quality-adjusted life expectancy to 0.07 quality-adjusted life-years, yielding an incremental cost-effectiveness ratio of €74,622 per quality-adjusted life-year gained.
Rapid-acting analog insulin is associated with beneficial outcomes in patients with type 1 diabetes and is likely to be considered cost effective in the German setting vs. regular human insulin.
KSB and KVB devised the research question. All authors were involved in devising the literature search strategy. WJV and RFP then ran the literature searches, screened the retrieved literature, and extracted the data used in the final analyses. All authors were subsequently involved in scrutinizing and, where necessary, revising the simulation plans for the final analyses. RFP ran the analyses in the PRIME Diabetes Model, which were cross-checked with the original data sources by WJV. RFP and WJV wrote the first draft of the manuscript, with KSB and KVB making substantive revisions prior to submission.
Compliance with Ethical Standards
The study was funded by Eli Lilly and Company.
Conflict of interest
Richard F. Pollock and William J. Valentine are full-time employees of Ossian Health Economics and Communications GmbH, which received consultancy fees from Eli Lilly and Company to conduct the analysis and for the preparation of the manuscript. Kristina S. Boye and Kate Van Brunt are full-time employees of Eli Lilly and Company, which manufactures the rapid-acting insulin Humalog (Insulin lispro) and other antidiabetic agents.
No patient-level data were used as part of the present study. As such, ethics approval and patient consent were neither required nor sought.
- 1.IDF Atlas, Version 6. 2015. https://www.idf.org/sites/default/files/EN_6E_Atlas_Full_0.pdf. Accessed 22 Dec 2015.
- 2.Bächle C, Icks A, Straßburger K, Flechtner-Mors M, Hungele A, Beyer P, Placzek K, Hermann U, Schumacher A, Freff M, Stahl-Pehe A, Holl RW. Rosenbauer J; DPV Initiative and the German BMBF Competence Network Diabetes Mellitus. Direct diabetes-related costs in young patients with early-onset, long-lasting type 1 diabetes. PLoS One. 2013;8(8):e70567.CrossRefPubMedPubMedCentralGoogle Scholar
- 8.IQWiG Reports. Commission No. A05-02. Rapid-acting insulin analogues in the treatment of diabetes mellitus type 1. 2007. www.iqwig.de/download/A05-02_Abschlussbericht_Kurzwirksame_Insulinanaloga_bei_Diabetes_mellitus_Typ_1.pdf. Accessed 16 Feb 2018.
- 11.Palmer AJ, Roze S, Valentine WJ, Minshall ME, Foos V, Lurati FM, Lammert M, Spinas GA. 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.CrossRefPubMedGoogle Scholar
- 12.Clarke PM, Gray AM, Briggs A, Farmer AJ, Fenn P, Stevens RJ, Matthews DR, Stratton IM. Holman RR; UKPDS Group. 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):1747–59.CrossRefPubMedGoogle Scholar
- 14.Farmer AJ, Stevens R, Hirst J, Lung T, Oke J, Clarke P, Glasziou P, Neil A, Dunger D, Colhoun HM, Pugh C, Wong G, Perera R, Shine B. Optimal strategies for identifying kidney disease in diabetes: properties of screening tests, progression of renal dysfunction and impact of treatment: systematic review and modelling of progression and cost-effectiveness. Health Technol Assess. 2014;18(14):1–128.CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Valentine W, Pollock RF, Saunders R, Bae J, Norrbacka K, Curtis B, Boye K. Predicting complications and long-term outcomes in type 1 diabetes: the PRIME Diabetes Model. Paper presented at the European Association for the Study of Diabetes Annual Meeting, Stockholm, 15–18 September 2015.Google Scholar
- 17.Boye KS, Lage ME, Treglia M, Lage MJ, Valentine W, Pollock RF, Saunders R. Verification and validation of health economic models for diabetes. Paper presented at the International Society for Pharmacoeconomics and Outcomes Research 18th Annual European Congress, Milan, 7–11 November 2015.Google Scholar
- 19.Raile K, Galler A, Hofer S, Herbst A, Dunstheimer D, Busch P, Holl RW. Diabetic nephropathy in 27,805 children, adolescents, and adults with type 1 diabetes: effect of diabetes duration, A1C, hypertension, dyslipidemia, diabetes onset, and sex. Diabetes Care. 2007;30(10):2523–8.CrossRefPubMedGoogle Scholar
- 21.Brunetti P, Muggeo M, Cattin L, Arcangeli A, Pozzilli P, Provenzano V, Francesconi A, Calatola P, Santeusanio F. Incidence of severe nocturnal hypoglycemia in patients with type 1 diabetes treated with insulin lispro or regular human insulin in addition to basal insulin glargine. Nutr Metab Cardiovasc Dis. 2010;20(7):519–26.CrossRefPubMedGoogle Scholar
- 22.World Health Organization. Global Health Observatory (GHO) data. Life tables. 2015. http://www.who.int/gho/mortality_burden_disease/life_tables/life_tables/en/. Accessed 16 Feb 2018.
- 25.Karges B, Rosenbauer J, Kapellen T, Wagner VM, Schober E, et al. Hemoglobin A1c levels and risk of severe hypoglycemia in children and young adults with type 1 diabetes from Germany and Austria: a trend analysis in a cohort of 37,539 patients between 1995 and 2012. PLoS Med. 2014;11(10):e1001742.CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Rote Liste® Service GmbH. Die Rote Liste. 2018. http://online.rote-liste.de/. Accessed 16 Feb 2018.
- 33.Laubner K, Molz K, Kerner W, et al. Daily insulin doses and injection frequencies of neutral protamine hagedorn (NPH) insulin, insulin detemir and insulin glargine in type 1 and type 2 diabetes: a multicenter analysis of 51 964 patients from the German/Austrian DPV-wiss database. Diabetes Metab Res Rev. 2014;30(5):395–404.CrossRefPubMedGoogle Scholar
- 36.Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen. Allgemeine Methoden 4.2. 2015. https://www.iqwig.de/download/IQWiG_General_Methods_Version_%204-2.pdf. Accessed 16 Feb 2018.
- 37.Schwarzer R, Rochau U, Saverno K, Jahn B, Bornschein B, Muehlberger N, Flatscher-Thoeni M, Schnell-Inderst P, Sroczynski G, Lackner M, Schall I, Hebborn A, Pugner K, Fehervary A, Brixner D, Siebert U. Systematic overview of cost-effectiveness thresholds in ten countries across four continents. J Comp Eff Res. 2015;4(5):485–504.CrossRefPubMedGoogle Scholar
- 42.Canadian Agency for Drugs and Technologies in Health. Second- and third-line pharmacotherapy for type 2 diabetes: update. CADTH optimal use reports. Ottawa, ON: CADTH; 2013.Google Scholar
- 44.Control Diabetes, Trial Complications. (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group. Mortality in type 1 diabetes in the DCCT/EDIC versus the general population. Diabetes Care. 2016;39(8):1378–83.Google Scholar