Sodium-Glucose Co-Transport Inhibition With Dapagliflozin in Type 2 Diabetes Mellitus

Abstract

Objective: Dapagliflozin, a novel inhibitor of renal sodium-glucose co-transporter 2, allows an insulin-independent approach to improve type 2 diabetes mellitus (T2DM) hyperglycemia. This multipledose study evaluated safety and efficacy of dapagliflozin in T2DM patients.

Research Design and Methods: T2DM patients were randomized to one of five dapagliflozin doses, metformin XR, or placebo for 12 weeks. The primary objective compared mean change from baseline in glycated hemoglobin (A1C). Other objectives included change in fasting plasma glucose (FPG), weight, adverse events, and laboratory measurements.

Results: After 12 weeks, dapagliflozin induced moderate glucosuria (52–85 g urinary glucose/day) and demonstrated significant glycemic improvements versus placebo (ΔA1C, −0.55 to −0.90%; ΔFPG, −16 to −31 mg/dl). Weight loss versus placebo was −1.3 to −2.0 kg. There was no change in renal function. Serum uric acid decreased, serum magnesium increased, serum phosphate increased at higher doses, and dose-related 24-h urine volume and hematocrit increased, all of small magnitude. Treatment-emergent adverse events were similar across all groups.

Conclusions: Dapagliflozin improves hyperglycemia and facilitates weight loss in T2DM patients by inducing controlled glucosuria with urinary loss of ∼200–300 kcalories/day. Dapagliflozin treatment demonstrates no persistent, clinically significant osmolarity, volume, or renal status changes.