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

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2014-11, Vol.16 (11), p.1111-1120
• Main Authors: Nauck, M A, Del Prato, S, Duran-Garcia, S, Rohwedder, K, Langkilde, A M, Sugg, J, Parikh, S J
• Format: Article
• Language: English
• Subjects: Antidiabetics; Blood pressure; Diabetes; Diabetes mellitus (non-insulin dependent); Hemoglobin; Hypoglycemia; Medical research; Metformin; Urinary tract; Weight; Women
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12327

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 18weeks according to tolerability and glycaemic response to a maximum of 10 and 20mg/day, respectively, as add-on therapies to metformin (≥1500mg/day) with a 156-week double-blind extension period. Data over 104weeks are reported here. Results In total, 53.1% of patients completed 104weeks of treatment. After the greater initial decrease (0-18weeks) 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%(-2.0mmol/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 -5.1kg (95% CI: -5.7,-4.4) and -3.9mmHg (95% CI: -6.1,-1.7), respectively. Over 104weeks, 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 2years, 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. [PUBLICATION ABSTRACT]