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 ( HbA1c ) with glipizide, the 18–104‐week HbA1c coefficient of failure ( CoF ) was lower with dapagliflozin (0.13%/year) than with glipizide (0.59%/year), resulting in significant dapagliflozin versus glipizide differences of −0.46%/year (95% CI −0.60,−0.33; p = 0.0001) for CoF and −0.18%(−2.0 mmol/mol) [95% CI −0.33(−3.6),−0.03(−0.3); p = 0.021] for 104‐week HbA1c . 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% CI : −5.7,−4.4) and −3.9 mmHg (95% CI : −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.