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.
RCT Entities:
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.
Authors: Kathryn M Thrailkill; Jeffry S Nyman; R Clay Bunn; Sasidhar Uppuganti; Katherine L Thompson; Charles K Lumpkin; Evangelia Kalaitzoglou; John L Fowlkes Journal: Bone Date: 2016-10-28 Impact factor: 4.398
Authors: Stuart J McGurnaghan; Liam Brierley; Thomas M Caparrotta; Paul M McKeigue; Luke A K Blackbourn; Sarah H Wild; Graham P Leese; Rory J McCrimmon; John A McKnight; Ewan R Pearson; John R Petrie; Naveed Sattar; Helen M Colhoun Journal: Diabetologia Date: 2019-01-10 Impact factor: 10.122
Authors: Serge A Jabbour; Juan P Frías; Elise Hardy; Azazuddin Ahmed; Hui Wang; Peter Öhman; Cristian Guja Journal: Diabetes Care Date: 2018-08-06 Impact factor: 19.112