• Diabetes Mellitus
• Hyperglycemia/Hypoglycemia
• Diabetes & Endocrinology Clinical Trials

• Endocrinology
• Diabetes & Metabolic Syndrome
• Diabetes Mellitus
• Hyperglycemia/Hypoglycemia
• Diabetes & Endocrinology Clinical Trials

Julio Rosenstock, MD, Dallas Diabetes and Endocrine Center, Dallas, Texas, USA, presented results from the Safety and Efficacy of Combination Saxagliptin & Dapagliflozin Added to Metformin to Treat Subjects With Type 2 Diabetes trial [NCT01606007]. This active-controlled, double-blind, parallel-group phase 3 study demonstrated that combined saxagliptin and dapagliflozin, when added to metformin, were more effective in reducing glucose than treatment with metformin alone in adults with type 2 diabetes mellitus (T2DM).

According to Dr Rosenstock, the sequential addition of a single glycemic control agent is the recommended approach for T2DM patients who are poorly controlled on metformin monotherapy. However, this approach may be inadequate, particularly when HbA_1c levels are significantly elevated.

The study aimed to investigate the efficacy and safety of early triple therapy that includes metformin and the concomitant initiation of dual oral therapy with the dipeptidyl peptidase 4 inhibitor saxagliptin and the sodium-glucose cotransporter 2 inhibitor dapagliflozin.

Patients (n = 534) were randomized to saxagliptin −5 mg + dapagliflozin-10 mg + metformin (n = 179), saxagliptin-5 mg + metformin + placebo (n = 176), or dapagliflozin-10 mg + metformin + placebo (n = 179). The study enrolled adults (> 18 years) with a body mass index ≤ 45 kg/m², HbA_1c levels ≥ 8% and ≤ 12%, and an estimated glomerular filtration rate ≥ 60 mL/min/1.73 m². All participants were receiving ≥ 1500 mg/d of metformin before randomization.

The primary end point was the adjusted mean change in baseline HbA_1c levels at week 24. At 24 weeks, the reduction in mean HbA_1c levels was significantly greater in patients treated with saxagliptin + dapagliflozin + metformin when compared with saxagliptin + metformin (−1.5% vs −0.9%; P < .001) and dapagliflozin + metformin (−1.5% vs −1.2%; P = .02;). Additionally, more patients in the saxagliptin + dapagliflozin + metformin group achieved a target HbA_1c < 7% (41% vs 18% vs 22%).

No deaths were reported in any of the groups. The incidence of serious adverse events (AEs) was similar in all 3 groups (1% vs 3% vs 1%). The incidence of AEs leading to treatment discontinuation was also similar (0.6% vs 0% vs 0%). With respect to AEs of special interest, the incidence of urinary tract infections was also similar in all 3 groups (0.6% vs 5% vs 4%), and the incidence of hypoglycemia was low (1% in all groups). Genital infections were not recorded in the saxagliptin + dapagliflozin + metformin group (0% vs 0.6% vs 6%).

In his concluding remarks, Dr Rosenstock stated that when compared with monotherapy, the addition of saxagliptin and dapagliflozin to metformin in poorly controlled TD2M patients led to greater reductions in HbA_1c and allowed more patients to achieve a target HbA_1c < 7%. Dual add-on therapy was also well tolerated and did not increase the risk of hypoglycemia in patients.

• © 2014 MD Conference Express®