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

There was little difference in BP between dual add-on saxagliptin plus dapagliflozin or single add-on saxagliptin or dapagliflozin to metformin. The proportion of patients who attained the BP quality measure of BP < 140/90 mm Hg was similar across the 3 treatments, as might be expected because most patients already met this target at baseline. However, as might be expected based on the mild diuretic effect and weight loss associated with SGLT-2 inhibitors [16,17], trends in BP favored groups treated with dapagliflozin.

Attainment of multiple treatment targets is desirable in reducing complications of diabetes. A significantly greater proportion of patients achieved both A1C < 7% and BP < 140/90 mm Hg when both saxagliptin and dapagliflozin were added to metformin compared with single-agent addition of either saxagliptin or dapagliflozin plus metformin. Similarly, a significantly greater proportion of patients achieved both A1C < 8% and BP < 140/90 mm Hg with dual addition of saxagliptin and dapagliflozin plus metformin compared with saxagliptin plus metformin. There was also a numerically greater number of patients who achieved both of these goals with triple therapy compared with dapagliflozin plus metformin, but this finding did not reach statistical significance. Clinically relevant NNT values ≤ 10 were observed for both composite outcomes for saxagliptin plus dapagliflozin plus metformin compared with saxagliptin plus metformin or dapagliflozin plus metformin after 24 weeks.

Despite advances in the medical management of T2D, a report published in 2013 showed that between 2007 and 2010, only 53% of patients achieved an A1C < 7.0% and only 19% simultaneously achieved all 3 American Diabetes Association (ADA) goals recommended for most patients at that time: A1C < 7.0%, BP < 130/80 mm Hg, and low-density lipoprotein cholesterol LDL-C < 100 mg/dL [18]. These data highlight a need for new approaches to help patients attain glycemic, BP, and cholesterol goals. Our results demonstrated that a higher proportion of patients attained glycemic and BP quality measures with dual add-on saxagliptin plus dapagliflozin compared with single add-on saxagliptin or dapagliflozin to metformin. As a result of recent updates for cholesterol management from the American College of Cardiology and the American Heart Association [19], attainment of a cholesterol level was retired as a diabetes quality measure and replaced with a recommendation for statin therapy use [20,21]. Although the current analysis did not include assessment of LDL, DPP-4 inhibitors have demonstrated neutral effects on lipids [22,23], and SGLT-2 inhibitors have demonstrated generally modest increases in LDL-C (placebo-adjusted change from baseline: 4.5%–8.0% for canagliflozin 100 and 300 mg/d, 3.9% for dapagliflozin 10 mg, and 2.3%–4.2% for empagliflozin 10 and 25 mg/d) [12,24,25], as well as increases in high-density lipoprotein cholesterol and reductions in triglycerides [26].

Current ADA guidelines recommend an individualized, stepwise approach to treatment with sequential addition of single oral antihyperglycemic agents for patients who do not achieve their glycemic goal in 3 months [27]. Although T2D may progress at different rates in different patients, T2D does generally progress over time [28], and the ADA and American Association of Clinical Endocrinologists treatment guidelines recommend initial dual add-on therapy for individuals with higher A1C, which is suggestive of more advanced disease [27,29]. For individuals requiring initial combination therapy, guidelines note that antihyperglycemic agents that have a low risk of hypoglycemia and low potential for weight gain should be preferentially selected [29]. Attainment of A1C ≤ 7%, the guideline recommendation considered appropriate for many patients, is associated with reductions in microvascular disease and, if attained soon after diagnosis of diabetes, studies have shown reductions in macrovascular disease with long-term follow-up [27,30,31]. However, it may be challenging to achieve A1C < 7% with the addition of single oral antihyperglycemic agents, especially in patients with higher A1C [32]. Less stringent A1C goals (eg, A1C < 8%) may be appropriate in individuals with a long duration of diabetes that is difficult to control, history of severe hypoglycemia, limited life expectancy, numerous comorbidities, and extensive complications or comorbidities, especially cardiovascular disease [27]. Given the shift toward individualized treatment plans with patient-specific treatment goals, it is valuable to understand how different treatment strategies effect attainment of guideline-recommended less stringent and more stringent glycemic targets that may be appropriate for certain patients.