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Once-weekly semaglutide is a novel glucagon-like peptide-1 (GLP-1) analog for the treatment of type 2 diabetes (T2D) that has been associated with greater reductions in glycated hemoglobin (HbA1c) and body weight versus GLP-1 receptor agonists dulaglutide, exenatide extended-release (ER), liraglutide and lixisenatide in the SUSTAIN trial program and a network meta-analysis (NMA). The aim of the present study was to assess the long-term cost-effectiveness of semaglutide versus all available GLP-1 receptor agonists in Denmark, using a clinically orientated treatment approach.
Outcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Baseline characteristics and treatment effects were sourced from the corresponding SUSTAIN trials and the NMA. Patients were assumed to initiate GLP-1 receptor agonist therapy and subsequently treatment-intensify according to clinical treatment guidelines, with addition of basal insulin and switching to basal-bolus insulin occurring when HbA1c exceeded recommended targets. Patients were assumed to receive a GLP-1 receptor agonist plus basal insulin therapy once HbA1c levels reached 7.5% and a basal-bolus insulin regimen once HbA1c exceeded 8.0%. Costs were captured in 2017 Danish kroner (DKK), with future costs and outcomes discounted at 3% per annum.
Primary analyses indicated that semaglutide 0.5 mg and 1 mg were associated with improvements in quality-adjusted life expectancy of 0.11 and 0.34 quality-adjusted life years, respectively, versus dulaglutide, achieved at cost savings of DKK 289 and DKK 13,416, respectively. Supporting analyses indicated that both doses of semaglutide were either cost-effective or dominant versus exenatide ER, liraglutide 1.2 mg and 1.8 mg and lixisenatide.
Semaglutide represents a cost-effective alternative to other GLP-1 receptor agonist therapies available in Denmark, demonstrating clinical benefits versus dulaglutide, exenatide ER, liraglutide and lixisenatide for the treatment of patients with T2D.
Novo Nordisk A/S.
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Supplementary material 1 (DOCX 56 kb)13300_2019_630_MOESM1_ESM.docx
International Diabetes Federation (IDF). IDF Diabetes Atlas, 8th edn. http://www.diabetesatlas.org/across-the-globe.html. Accessed May 8, 2018.
Sortsø C, Green A, Jensen PB, Emneus M. Societal costs of diabetes mellitus in Denmark. Diabet Med. 2016;33(7):877–85. CrossRef
Gæde J, Oellgaard J, Ibsen R, et al. A cost analysis of intensified vs conventional multifactorial therapy in individuals with type 2 diabetes: a post hoc analysis of the Steno-2 study. Diabetologia. 2019;62(1):147–55. CrossRef
Ismail-Beigi F, Craven T, Banerji MA, ACCORD trial group, 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. CrossRef
Patel A, MacMahon S, Chalmers J, ADVANCE Collaborative Group, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–72. CrossRef
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–53. CrossRef
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. CrossRef
Stettler C, Allemann S, Jüni P, et al. Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: meta-analysis of randomized trials. Am Heart J. 2006;152(1):27–38. CrossRef
Griffin SJ, Borch-Johnsen K, Davies MJ, et al. Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial. Lancet. 2011;378(9786):156–67. CrossRef
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. CrossRef
Kearney PM, Blackwell L, Collins R, Cholesterol Treatment Trialists’ Collaborators, 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(9607):117–25. CrossRef
UK Prospective Diabetes Study (UKPDS) Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317(7160):703–13. CrossRef
Gaede P, Valentine WJ, Palmer AJ, et al. Cost-effectiveness of intensified versus conventional multifactorial intervention in type 2 diabetes: results and projections from the Steno-2 study. Diabetes Care. 2008;31(8):1510–5. CrossRef
Herman WH, Ye W, Griffin SJ, et al. Early detection and treatment of type 2 diabetes reduce cardiovascular morbidity and mortality: a simulation of the results of the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen-Detected Diabetes in Primary Care (ADDITION-Europe). Diabetes Care. 2015;38(8):1449–55. CrossRef
Holm AL, Andersen GS, Jørgensen ME, et al. Is the rule of halves framework relevant for diabetes care in Copenhagen today? A register-based cross-sectional study. BMJ Open. 2018;8:e023211. CrossRef
Christensen DH, Nicolaisen SK, Berencsi K, et al. Danish Centre for Strategic Research in Type 2 Diabetes (DD2) project cohort of newly diagnosed patients with type 2 diabetes: a cohort profile. BMJ Open. 2018;8:e017273. CrossRef
Thomsen RW, Baggesen LM, Søgaard M, et al. Early glycaemic control in metformin users receiving their first add-on therapy: a population-based study of 4,734 people with type 2 diabetes. Diabetologia. 2015;58(10):2247–53. CrossRef
Inzucchi SE, Bergenstal RM, Buse JB, American Diabetes Association [ADA] and European Association for the Study of Diabetes [EASD], et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35(6):1364–79. CrossRef
Nauck M, Weinstock RS, Umpierrez GE, Guerci B, Skrivanek Z, Milicevic Z. Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a Randomized Controlled Trial (AWARD-5). Diabetes Care. 2014;37(8):2149–58. CrossRef
Tuttle KR, Lakshmanan MC, Rayner B, et al. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol. 2018;6(8):605–17. CrossRef
Russell-Jones D, Vaag A, Schmitz O, Liraglutide Effect and Action in Diabetes 5 [LEAD-5] met + SU Study Group, et al. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met + SU): a randomised controlled trial. Diabetologia. 2009;52(10):2046–55. CrossRef
Anderson SL, Trujillo JM. Basal insulin use with GLP-1 receptor agonists. Diabetes Spectr. 2016;29(3):152–60. CrossRef
Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–22. CrossRef
Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834–44. CrossRef
Eli Lilly. Trulicity ® (dulaglutide) demonstrates superiority in reduction of cardiovascular events for broad range of people with type 2 diabetes. 2018. https://investor.lilly.com/node/39796/pdf. Accessed Nov 22, 2018.
Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018;392:1519–29. CrossRef
Davies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018;2018(61):2461–98. CrossRef
Dansk Sesklab for Almen Medicin (DSAM) [Danish Company for General Medicine]. Farmakologisk behandling af type 2-diabetes [Pharmacological treatment of type 2 diabetes]. 2018. https://vejledninger.dsam.dk/media/files/4/guidelines-2018-final.pdf. Accessed Jan 23, 2019.
American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2019. Diabetes Care. 2019;42(Supplement 1):S90–S102.
European Medicines Agency. EPAR summary for the public: Ozempic/semaglutide. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/004174/WC500244166.pdf. Accessed June 1, 2018.
Pratley RE, Aroda VR, Lingvay I, et al. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018;6(4):275–86. CrossRef
Ahmann AJ, Capehorn M, Charpentier G, et al. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): a 56-week, open-label, randomized clinical trial. Diabetes Care. 2018;41(2):258–66. CrossRef
Witkowski M, Wilkinson L, Webb N, Weids A, Glah D, Vrazic H. A systematic literature review and network meta-analysis comparing once-weekly semaglutide with other GLP-1 receptor agonists in patients with type 2 diabetes previously receiving 1–2 oral anti-diabetic drugs. Diabetes Ther. 2018;9(3):1149–67. CrossRef
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):S27–40. CrossRef
McEwan P, Foos V, Palmer JL, Lamotte M, Lloyd A, Grant D. Validation of the IMS CORE Diabetes Model. Value Health. 2014;17(6):714–24. CrossRef
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):S5–26. CrossRef
World Health Organization. Global Health Observatory data repository: Life tables by country—Denmark. 2015. http://apps.who.int/gho/data/view.main.60450?lang=en. Accessed June 1, 2018.
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):129–47. CrossRef
Hunt B, Mocarski M, Valentine WJ, Langer J. Evaluation of the long-term cost-effectiveness of IDegLira versus liraglutide added to basal insulin for patients with type 2 diabetes failing to achieve glycemic control on basal insulin in the USA. J Med Econ. 2017;20(7):663–70. CrossRef
Hunt B, Vega-Hernandez G, Valentine WJ, Kragh N. Evaluation of the long-term cost-effectiveness of liraglutide versus lixisenatide for treatment of type 2 diabetes mellitus in the UK setting. Diabetes Obes Metab. 2017;19(6):842–9. CrossRef
American Diabetes Association Consensus Panel. Guidelines for computer modeling of diabetes and its complications. Diabetes Care. 2004;27(9):2262–5. CrossRef
Lægemiddelstyrelsen [Danish Medicines Agency]. Erfaringer med sundhedsøkonomiske analyser i ansøgninger om generelt tilskud til lægemidler [Guidelines for health-economic analyses for novel pharmaceuticals]. 2004. https://laegemiddelstyrelsen.dk/da/tilskud/generelle-tilskud/ansoegning/sundhedsoekonomiske-analyser/erfaringer-med-sundhedsoekonomiske-analyser-i-ansoegninger-om-generelt-tilskud-til-laegemidler#47. Accessed Nov 1, 2018.
European Medicines Agency. Trulicity. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002825/human_med_001821.jsp&mid=WC0b01ac058001d124. Accessed June 1, 2018.
Briggs AH, Weinstein MC, Fenwick EA, Karnon J, Sculpher MJ, Paltiel AD, ISPOR-SMDM Modeling Good Research Practices Task Force. Model parameter estimation and uncertainty: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force–6. Value Health. 2012;15(6):835–42. CrossRef
Viberti G, Kahn SE, Greene DA, et al. A Diabetes Outcome Progression Trial (ADOPT): an international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes. Diabetes Care. 2002;25(10):1737–43. CrossRef
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. CrossRef
Khunti K, Alsifri S, Aronson R, Berković MC, et al. Rates and predictors of hypoglycaemia in 27 585 people from 24 countries with insulin-treated type 1 and type 2 diabetes: the global HAT study. Diabetes Obes Metab. 2016;18(9):907–15. CrossRef
Lægemiddelstyrelsen [Danish Medicines Agency]. Medicinpriser. 2018. https://www.medicinpriser.dk/?lng=2. Accessed June 13, 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):462–70. CrossRef
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. CrossRef
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(1):90. CrossRef
Viljoen A, Hoxer CS, Johansen P, Malkin S, Hunt B, Bain SC. Evaluation of the long-term cost-effectiveness of once-weekly semaglutide versus dulaglutide for the treatment of type 2 diabetes mellitus in the UK. Diabetes Obes Metab. 2019;21(3):611–21. CrossRef
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. CrossRef
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. CrossRef
Rawshani AI, Rawshani AR, Franzén S, et al. Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2018;379:633–44. CrossRef
Johansen P, Håkan-Bloch J, Liu AR, Bech PG, Persson S, Leiter LA. Cost Effectiveness of Once-Weekly Semaglutide Versus Once-Weekly Dulaglutide in the Treatment of Type 2 Diabetes in Canada. Pharmacoecon Open. 2019. https://doi.org/10.1007/s41669-019-0131-6 (epub ahead of print).
Tikkanen CK, Johansen P, Hunt B, Malkin S, Pollock RF. Once-weekly semaglutide provides better health outcomes compared to dulaglutide as dual therapy in the treatment of type 2 diabetes: a cost-effectiveness analysis. Diabetologia. 2018;61(Supplement 1):S426–7.
Snorgaard O, Kristensen JK, Balasubramaniam K et al. Farmakologisk behandling af type 2-diabetes [Pharmacological treatment of type 2 diabetes]. 2018. https://vejledninger.dsam.dk/media/files/4/guidelines-2018-final.pdf. Accessed Nov 27, 2018.
Ahrén B, Masmiquel L, Kumar H, et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol. 2017;5(5):341–54. CrossRef
Aroda VR, Bain SC, Cariou B, et al. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol. 2017;5(5):355–66. CrossRef
Sharma R, Wilkinson L, Vrazic H, et al. Comparative efficacy of once-weekly semaglutide and SGLT-2 inhibitors in type 2 diabetic patients inadequately controlled with metformin monotherapy: a systematic literature review and network meta-analysis. Curr Med Res Opin. 2018;34(9):1595–603. CrossRef
Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23):2247–57. CrossRef
Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017;377(13):1228–39. CrossRef
Aagaard DT, Nielsen Christiansen M, Mogensen M, et al. Cardiovascular risk according to add-on therapy in patients with type 2 diabetes. Eur Heart J. 2018;39:492. CrossRef
EUnetHTA. European Network for Health Technology. Guideline—comparators & comparisons: direct and indirect comparisons. February 2013. http://www.eunethta.eu/sites/5026.fedimbo.belgium.be/files/Direct%20and%20indirect%20comparisons.pdf. Accessed Dec 13, 2017.
Dias SW, N J, Sutton AJ, Ades AE. NICE DSU technical support document 1: introduction to evidence synthesis for decision making, 2011; last updated April 2012. http://scharr.dept.shef.ac.uk/nicedsu/wp-content/uploads/sites/7/2016/03/TSD1-Introduction.final_.08.05.12.pdf. Accessed Dec 13, 2017.
- Management of Patients with Type 2 Diabetes with Once-Weekly Semaglutide Versus Dulaglutide, Exenatide ER, Liraglutide and Lixisenatide: A Cost-Effectiveness Analysis in the Danish Setting
Christian Klyver Tikkanen
Richard Fulton Pollock
Samuel Joseph Paul Malkin
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Research, treatment and education of diabetes and related disorders
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