Durability of glycaemic efficacy over 2 years with dapagliflozin versus glipizide as add-on therapies in patients whose type 2 diabetes mellitus is inadequately controlled with metformin

Aims: To assess the long-term glycaemic durability, safety and tolerability of dapagliflozin versus glipizide as add-on therapies in patients with type 2 diabetes inadequately controlled by metformin alone. Methods: This was a 52-week, randomised, double-blind study of dapagliflozin (n = 406) versus glipizide (n = 408), uptitrated over 18 weeks according to tolerability and glycaemic response to a maximum of 10 and 20 mg/day, respectively, as add-on therapies to metformin (>1500 mg/day) with a 156-week double-blind extension period. Data over 104 weeks are reported here. Results: In total, 53.1% of patients completed 104 weeks of treatment. After the greater initial decrease (0-18 weeks) in glycated haemoglobin (HbAlc) with glipizide, the 18-104-week HbAlc coefficient of failure (CoF) was lower with dapagliflozin (0.1301o/year) than with glipizide (0.590/o/year), resulting in significant dapagliflozin versus glipizide differences of 0.460,folyear (95% Cl 0.60,-0.33; p =00001) for CoF and 0.180/0-2.0 mmollmol) [950to Cl 0.33(-3.6),-0.03(-0.3); p =0.0211 for 104-week HbAl c. Dapagliflozin produced sustained reductions in weight and systolic blood pressure, whereas glipizide increased weight and systolic blood pressure, giving 104-week dapagliflozin versus glipizide differences of 5.1 kg (95% Cl: 5.7,-4.4) and 3.9 mmHg (95% Cl: 6.1,-1.7), respectively. Over 104 weeks, the hypoglycaemia rate was 10-fold lower with dapagliflozin than with glipizide (4.2 vs. 45.8%), whereas patient proportions with events suggestive of genital infection and of urinary tract infection (UTI) were greater with dapagliflozin (14.8 and 13.5%, respectively) than with glipizide (2.9 and 9.1%, respectively). Conclusions: Over 2 years, compared with glipizide, dapagliflozin demonstrated greater glycaemic durability, sustained reductions in weight and systolic blood pressure and a low hypoglycaemia rate; however, genital infections and UTIs occurred more frequently.