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 https://doi.org/10.1007/s13300-018-0430-4 ORIGINAL RESEARCH 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 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 Received: March 7, 2018 Ó The Author(s) 2018 ABSTRACT Introduction: 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. Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.6128024. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13300018-0430-4) contains supplementary material, which is available to authorized users. R. F. Pollock (&)
W. J. Valentine Ossian Health Economics and Communications GmbH, Basel, Switzerland e-mail: S. P. Marso HCA Midwest Health Heart and Vascular Institute, Kansas City, MO, USA J. Gundgaard
N. Hallén
L. L. Hansen
D. Tutkunkardas Novo Nordisk A/S, Søborg, Denmark J. B. Buse University of North Carolina School of Medicine, Medicine/Endocrinology, Chapel Hill, NC, USA Methods: 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. Results: 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 qualityadjusted 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. Conclusion: The present short-term modeling analysis found that for the basal–bolus Diabetes Ther 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. Funding: Novo Nordisk A/S. Trial Registration: ClinicalTrials.gov identifier, NCT01959529. Keywords: Cardiovascular outcome trial; Cost; Cost-effective; Diabetes; Hypoglycemia; Insulin degludec; QALY; United Kingdom INTRODUCTION Healthcare systems in many countries are under increasing financial pressure due to the demographic challenge of aging populations and the growing burden of chronic diseases, including diabetes [1]. Globally, one in 11 adults (425 million) has diabetes, of which type 2 diabetes makes up around 90% of cases, with the total cost of diabetes to healthcare systems estimated to be USD 727 billion in 2017 [2]. The cost of treating diabetes-related complications is substantial and in many healthcare systems exceeds the cost of blood-glucose-lowering medication [3]. With increasing constraints on healthcare budgets, health economic evaluations, including cost-utility analyses (CUA), are playing an increasingly important role in decisions to allocate resources between therapy areas and interventions. CUA, a special type of cost-effectiveness analysis, compares the costs of new interventions with their outcomes measured in utility-based units, most commonly the quality-adjusted life-year (QALY). This enables the comparison of alternative interventions according to cost per QALY gained, and assists in the efficient allocation of resources to achieve maximum healthcare gains within the constraints of a limited budget [4]. Episodes of severe hypoglycemia are becoming increasingly common, particularly as attention focuses on intensive glycemic control [5–7]. In the Hypoglycaemia Assessment Tool (HAT) study, 8.9% of patients with type 2 diabetes reported an episode of severe hypoglycemia during the 4-week prospective study [8]. Severe hypoglycemic events requiring hospitalization can pose a significant financial burden on healthcare systems: in the UK, the average direct medical cost of an event was estimated at over GBP 1300 in patients with type 2 diabetes [7]. Hypoglycemia has an acute, negative impact on clinical outcomes, including an increased risk of falls, fractures, cardiovascular (CV) events, coma, dementia, neurological conditions, and death, but can also have an adverse effect on longer-term diabetes management due to the fear of hypoglycemia [9–14]. Insulin degludec (degludec) is a basal insulin with an ultralong duration of action and a stable glucose-lowering profile [15]. Studies of the pharmacodynamics of degludec and another long-acting insulin analog, insulin glargine 100 units/mL (glargine U100), have confirmed the lower day-to-day and within-day variability in glucose-lowering effect with degludec compared with glargine U100 [16, 17]. Phase 3 clinical studies have established that similar improvements in glycemic control can be achieved with fewer hypoglycemic episodes, particularly nocturnal hypoglycemia, with degludec versus glargine U100 across a broad spectrum of patients with diabetes [18–20]. Recently, results from the first double-blind, active-comparator cardiovascular outcome trial (CVOT) of a specific antihyperglycemic therapy were published [21, 22]. DEVOTE (NCT01959529) evaluated the CV safety of degludec relative to glargine U100 in patients with type 2 diabetes at a heightened risk of CV complications [22]. In DEVOTE, degludec was noninferior to glargine U100 in terms of the incidence of CV events [22]. Furthermore, the trial demonstrated a significant reduction in the risk of severe hypoglycemia for degludec versus glargine U100 at a similar level of glycemic control [22]. The present evaluation focused on the subgroup of patients who started DEVOTE on a basal–bolus regimen. 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