Original Research

Quality Measure Attainment After Add-on Therapy of Both Saxagliptin and Dapagliflozin to Metformin Versus Single Add-On of Saxagliptin or Dapagliflozin

Journal of Clinical Outcomes Management. 2016 September;23(9)

Author(s):

References

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From the Ochsner Diabetes Clinical Research Unit, Frank Riddick Diabetes Institute, Department of Endocrinology, Ochsner Medical Center, New Orleans, LA (Dr. Blonde), and AstraZeneca, Gaithersburg, MD (Drs. Sheehan, Barrett, and Garcia-Sanchez).

Abstract

Objective: To evaluate diabetes care quality measure attainment, specifically, blood glucose and blood pressure (BP) control, with saxagliptin, a dipeptidyl peptidase-4 inhibitor, and dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, added singly or as dual add-on therapy in patients with type 2 diabetes inadequately controlled with metformin alone.
Methods: Analysis of a phase 3, randomized, double-blind, active-controlled, parallel-group trial was conducted. Patients were randomized 1:1:1 to receive saxagliptin 5 mg/d plus dapagliflozin 10 mg/d, saxagliptin 5 mg/d, or dapagliflozin 10 mg/d as add-on to metformin 1500 to 2000 mg/d. Assessments included attainment of individual and composite glycated hemoglobin (A1C) and BP measures at 24 weeks of treatment.
Results: Compared with single add-on saxagliptin or dapagliflozin, dual add-on saxagliptin plus dapagliflozin to metformin was associated with significantly more patients attaining the individual quality measures of A1C < 7% and A1C < 8%. Similarly, dual add-on saxagliptin plus dapagliflozin was associated with significantly more patients attaining the composite quality measures A1C < 7% and BP < 140/90 mm Hg and A1C < 8% and BP < 140/90 mmHg (vs saxagliptin plus metformin).
Conclusion: Dual add-on saxagliptin plus dapagliflozin to metformin was associated with a higher proportion of patients achieving glycemic and BP quality measures compared with single add-on saxagliptin or dapagliflozin.

Assessment of performance is a focus of many health care organizations as a means to evaluate and improve the quality of health care. Standardized performance measures have been developed to improve quality of care as well as to allow for comparative assessment of health plans and to support pay for performance models [1]. A widely used set of performance measures is the Healthcare Effectiveness Data and Information Set or HEDIS [2,3], measures that are maintained by the National Committee for Quality Assurance [4,5] and used by most US health plans [6].

Type 2 diabetes (T2D) is a focus of quality measure assessment and performance improvement because of its high prevalence, substantial personal and economic impact on society, high morbidity and mortality, and because it is a condition that requires coordinated care. Important outcome measures for diabetes include blood glucose control and blood pressure (BP) control. HEDIS measures for T2D include a glycated hemoglobin (A1C) > 9%, indicating poor glucose control, < 8%, indicating good control, and < 7%, a more stringent measure of good glycemic control. The HEDIS measure for BP in T2D is < 140/90 mm Hg, which is considered good BP control. All of these HEDIS measures are currently or were previously (A1C < 7%) endorsed by the National Quality Forum [1,7–10]. Endorsement of a quality measure by the NQF indicates that the measure has been thoroughly evaluated, meets specific criteria, and is based on recognized standards of care grounded in evidence-based medicine [1].

A number of oral agents are utilized in the treatment of diabetes. Saxagliptin, an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, and dapagliflozin, an oral sodium-glucose cotransporter-2 (SGLT-2) inhibitor, are indicated as adjuncts to diet and exercise in adults with T2D [11,12]. Saxagliptin inhibits DPP-4, and thereby reduces fasting and postprandial glucose concentrations by preventing degradation of the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide [13]. Dapagliflozin reduces blood glucose concentrations by inhibiting glucose reabsorption in the proximal tubule of the kidney, which results in enhanced urinary glucose excretion [14]. Because their mechanisms of action are glucose-dependent, both saxagliptin and dapagliflozin have a low intrinsic potential to cause hypoglycemia [13,14]. In a randomized, double-blind study of patients with T2D inadequately controlled with metformin, Rosenstock et al assessed the efficacy and safety of dual add-on of saxagliptin plus dapagliflozin versus saxagliptin and dapagliflozin added on alone (ClinicalTrials.gov identifier, NCT01606007) [15]. The dual add-on therapy resulted in a greater adjusted mean reduction from baseline in A1C at week 24 (–1.47%) compared with either saxagliptin (–0.88%) or dapagliflozin (–1.20%) alone added to metformin; the difference for dual add-on saxagliptin plus dapagliflozin to metformin vs. single add-on saxagliptin and single add-on dapagliflozin was –0.59% ( P < 0.001) and –0.27% ( P = 0.0166), respectively. The incidence of adverse events was similar across the 3 treatment groups, and hypo-glycemia was infrequent (1%), with no reports of severe hypoglycemia events (symptomatic events with glucose ≤ 54 mg/dL requiring assistance).