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04-30-2018 | Insulin degludec | Article

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

Journal: Diabetes Therapy

Authors: Richard F. Pollock, William J. Valentine, Steven P. Marso, Jens Gundgaard, Nino Hallén, Lars L. Hansen, Deniz Tutkunkardas, John B. Buse, On behalf of the DEVOTE Study Group

Publisher: Springer Healthcare



The aim of this study was to evaluate the short-term cost-utility of insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) for the treatment of type 2 diabetes in the basal–bolus subgroup of the head-to-head cardiovascular (CV) outcome trial, DEVOTE.


A cost-utility analysis was conducted over a 2-year time horizon using a decision analytic model to compare costs in patients receiving once daily degludec or glargine U100, both as part of a basal–bolus regimen, in addition to standard care. Clinical outcomes and patient characteristics were taken exclusively from DEVOTE, whilst health-related quality of life utilities and UK-specific costs (expressed in 2016 GBP) were obtained from the literature. The analysis was conducted from the perspective of the National Health Service.


Degludec was associated with mean cost savings of GBP 28.78 per patient relative to glargine U100 in patients with type 2 diabetes at high CV risk. Cost savings were driven by the reduction in risk of diabetes-related complications with degludec, which offset the higher treatment costs relative to glargine U100. Degludec was associated with a mean improvement of 0.0064 quality-adjusted life-years (QALYs) compared with glargine U100, with improvements driven predominantly by lower rates of severe hypoglycemia with degludec versus glargine U100. Improvements in quality-adjusted life expectancy combined with cost neutrality resulted in degludec being dominant over glargine U100. Sensitivity analyses demonstrated that the incremental cost-utility ratio was stable to variations in the majority of model inputs.


The present short-term modeling analysis found that for the basal–bolus subgroup of patients in DEVOTE, with a high risk of CV events, degludec was cost neutral (no additional costs) compared with glargine U100 over a 2-year time horizon in the UK setting. Furthermore, there were QALY gains with degludec, particularly due to the reduction in the risk of severe hypoglycemia.


Novo Nordisk A/S.

Trial Registration identifier, NCT01959529.
NCD Risk Factor Collaboration. Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet. 2016;387:1513–30. CrossRef
International Diabetes Federation. IDF diabetes atlas. Brussels: IDF; 2017.
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.
Robinson R. Cost-utility analysis. BMJ. 1993;307:859–62. PubMedPubMedCentralCrossRef
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. PubMedCrossRef
Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405–12. PubMedPubMedCentralCrossRef
Holbrook T, Tang Y, Das R, et al. Direct medical costs of severe hypoglycaemic events in patients with type 2 diabetes in England: a retrospective database study. Int J Clin Pract. 2017;71:e12958. CrossRef
Khunti K, Alsifri S, Aronson R, 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;18:907–15. PubMedPubMedCentralCrossRef
Leiter LA, Yale JF, Chiasson J-L, Harris SB, Kleinstiver P, Sauriol L. Assessment of the impact of fear of hypoglycemic episodes on glycemic and hypoglycemic management. Can J Diabetes. 2005;29:186–92.
Goto A, Arah OA, Goto M, Terauchi Y, Noda M. Severe hypoglycaemia and cardiovascular disease: systematic review and meta-analysis with bias analysis. BMJ. 2013;347:f4533. PubMedCrossRef
Johnston SS, Conner C, Aagren M, Ruiz K, Bouchard J. Association between hypoglycaemic events and fall-related fractures in Medicare-covered patients with type 2 diabetes. Diabetes Obes Metab. 2012;14:634–43. PubMedCrossRef
Zoungas S, Patel A, Chalmers J, et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med. 2010;363:1410–8. PubMedCrossRef
Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA. 2009;301:1565–72. PubMedPubMedCentralCrossRef
Bloomfield HE, Greer N, Newman D, et al. Predictors and consequences of severe hypoglycemia in adults with diabetes—a systematic review of the evidence. VA-ESP Project #09-009. Washington, DC: Department of Veterans Affairs; 2012.
Heise T, Nosek L, Bottcher SG, Hastrup H, Haahr H. Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect in type 2 diabetes. Diabetes Obes Metab. 2012;14:944–50. PubMedCrossRef
Heise T, Kaplan K, Haahr HL. Day-to-day and within-day variability in glucose-lowering effect between insulin degludec and insulin glargine (100 U/mL and 300 U/mL): a comparison across studies. J Diabetes Sci Technol. 2018;12(2):356–63.
Heise T, Hermanski L, Nosek L, Feldman A, Rasmussen S, Haahr H. Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes Obes Metab. 2012;14:859–64. PubMedCrossRef
Ratner R, Gough SC, Mathieu C, et al. Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials. Diabetes Obes Metab. 2013;15:175–84. PubMedCrossRef
Wysham C, Bhargava A, Chaykin L, et al. Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 2 diabetes: the SWITCH 2 randomized clinical trial. JAMA. 2017;318:45–56. PubMedPubMedCentralCrossRef
Lane W, Bailey TS, Gerety G, et al. Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 1 diabetes: the SWITCH 1 randomized clinical trial. JAMA. 2017;318:33–44. PubMedPubMedCentralCrossRef
Marso SP, McGuire DK, Zinman B, 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;179:175–83. PubMedCrossRef
Marso SP, McGuire DK, Zinman B, et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med. 2017;377:723–32. PubMedPubMedCentralCrossRef
American Diabetes Association. Standards of medical care in diabetes 2017. Diabetes Care. 2017;40:S64–74. CrossRef
Zoungas S, Woodward M, Li Q, 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;57:2465–74. PubMedCrossRef
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;7:45–60. PubMedPubMedCentralCrossRef
Meneghini L, Mersebach H, Kumar S, Svendsen AL, Hermansen K. Comparison of 2 intensification regimens with rapid-acting insulin aspart in type 2 diabetes mellitus inadequately controlled by once-daily insulin detemir and oral antidiabetes drugs: the step-wise randomized study. Endocr Pract. 2011;17:727–36. PubMedCrossRef
Barendse S, Singh H, Frier BM, Speight J. The impact of hypoglycaemia on quality of life and related patient-reported outcomes in type 2 diabetes: a narrative review. Diabet Med. 2012;29:293–302.
Brod M, Christensen T, Thomsen TL, Bushnell DM. The impact of non-severe hypoglycemic events on work productivity and diabetes management. Value Health. 2011;14:665–71. PubMedCrossRef
Bron M, Marynchenko M, Yang H, Yu AP, Wu EQ. Hypoglycemia, treatment discontinuation, and costs in patients with type 2 diabetes mellitus on oral antidiabetic drugs. Postgrad Med. 2012;124:124–32. PubMedCrossRef
Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care. 2013;36:1384–95. PubMedPubMedCentralCrossRef
National Institute for Health and Care Excellence. NICE process and methods guides. Guide to the methods of technology appraisal. 2013. Available at: https://​www.​nice.​org.​uk/​process/​pmg9/​chapter/​the-reference-case. Accessed November 2017.
MIMS. MIMS monthly index of medical specialities. 2017. Available at: https://​www.​mims.​co.​uk/​. Accessed October 2017.
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;32:459–66. PubMedCrossRef
Hammer M, Lammert M, Mejias SM, Kern W, Frier BM. Costs of managing severe hypoglycaemia in three European countries. J Med Econ. 2009;12:281–90. PubMedCrossRef
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 Making. 2002;22:340–9. PubMedCrossRef
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. PubMedPubMedCentralCrossRef
Personal Social Services Research Unit. The hospital and community health services index. 2016. Available at: http://​www.​pssru.​ac.​uk/​pub/​uc/​uc2016/​sources-of-information.​pdf. Accessed October 2017.
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;8:129–47. PubMedPubMedCentralCrossRef
Sullivan PW, Ghushchyan VH. EQ-5D scores for diabetes-related comorbidities. Value Health. 2016;19:1002–8. PubMedCrossRef
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. PubMedCrossRef
Hayes A, Arima H, Woodward M, et al. Changes in quality of life associated with complications of diabetes: results from the ADVANCE study. Value Health. 2016;19:36–41. PubMedCrossRef
Boye KS, Matza LS, Walter KN, Van BK, Palsgrove AC, Tynan A. Utilities and disutilities for attributes of injectable treatments for type 2 diabetes. Eur J Health Econ. 2011;12:219–30. PubMedCrossRef
Evans M, Jensen HH, Bogelund M, Gundgaard J, Chubb B, Khunti K. Flexible insulin dosing improves health-related quality-of-life (HRQoL): a time trade-off survey. J Med Econ. 2013;16:1357–65. PubMedCrossRef
Waugh N, Cummins E, Royle P, et al. Newer agents for blood glucose control in type 2 diabetes: systematic review and economic evaluation. Health Technol Assess. 2010;14:1–248. PubMed
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;22:1523–34. PubMedCrossRef
Peyrot M, Barnett AH, Meneghini LF, Schumm-Draeger PM. Insulin adherence behaviours and barriers in the multinational global attitudes of patients and physicians in insulin therapy study. Diabet Med. 2012;29:682–9. PubMedPubMedCentralCrossRef
Fidler C, Elmelund CT, Gillard S. Hypoglycemia: an overview of fear of hypoglycemia, quality-of-life, and impact on costs. J Med Econ. 2011;14:646–55. PubMedCrossRef
Nicolucci A, Kovacs Burns K, Holt RI, et al. Diabetes Attitudes, Wishes and Needs second study (DAWN2): cross-national benchmarking of diabetes-related psychosocial outcomes for people with diabetes. Diabet Med. 2013;30:767–77.
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;18:56–68. PubMedCrossRef
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;8:275–91. PubMedPubMedCentralCrossRef
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;16:366–75. PubMedCrossRef
Brod M, Wolden M, Christensen T, Bushnell DM. Understanding the economic burden of nonsevere nocturnal hypoglycemic events: impact on work productivity, disease management, and resource utilization. Value Health. 2013;16:1140–9. PubMedCrossRef
Schnell O, Ryden L, Standl E, Ceriello A. Current perspectives on cardiovascular outcome trials in diabetes. Cardiovasc Diabetol. 2016;15:139. PubMedPubMedCentralCrossRef
Bagust A, Beale S. Modelling EuroQol health-related utility values for diabetic complications from CODE-2 data. Health Econ. 2005;14:217–30. PubMedCrossRef

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