Stephan Matthaei1, Keith Bowering2, Katja Rohwedder3, Anke Grohl4, Shamik Parikh5. 1. Diabetes-Zentrum Quakenbrück, Quakenbrück, Germany s.matthaei@ckq-gmbh.de. 2. University of Alberta, Edmonton, Alberta, Canada. 3. AstraZeneca, Wedel, Germany. 4. Aptiv Solutions, Köln, Germany. 5. AstraZeneca, Wilmington, DE.
Abstract
OBJECTIVE: To evaluate the efficacy and safety of dapagliflozin in patients with type 2 diabetes inadequately controlled withmetformin and sulfonylurea. RESEARCH DESIGN AND METHODS: Patients with HbA1c of 7.0% (53 mmol/mol) to 10.5% (91 mmol/mol) receiving sulfonylurea and metformin were randomized to receive dapagliflozin 10 mg/day (n = 109) or placebo (n = 109) for 24 weeks. RESULTS: HbA1c (baseline: dapagliflozin 8.08% [65 mmol/mol]; placebo 8.24% [67 mmol/mol]) and fasting plasma glucose (baseline: dapagliflozin 167.4 mg/dL [9.29 mmol/L]; placebo 180.5 mg/dL [10.02 mmol/L]) significantly improved from baseline with dapagliflozin (placebo-subtracted change -0.69% [-7.5 mmol/mol], P < 0.0001; -33.5 mg/dL [-1.86 mmol/L], P < 0.0001, respectively). More patients achieved a therapeutic glycemic response (HbA1c <7.0% [53 mmol/mol]) with dapagliflozin (31.8%) versus placebo (11.1%) (P < 0.0001). Body weight and systolic blood pressure were significantly reduced from baseline over 24 and 8 weeks, respectively, with dapagliflozin (placebo-subtracted change -2.1 kg, P < 0.0001; -3.8 mmHg, P = 0.0250). Patients receiving dapagliflozin showed placebo-subtracted increases in total, LDL, and HDL cholesterol (11.4 mg/dL, P = 0.0091; 11.4 mg/dL, P = 0.0030; 2.2 mg/dL, P = 0.0172, respectively) with no change in LDL/HDL cholesterol ratio (0.1; P = 0.2008) or triglycerides (-16.5 mg/dL; P = 0.1755). Adverse events occurred in 48.6% of patients receiving dapagliflozin and 51.4% receiving placebo. Significantly more patients with dapagliflozin compared with placebo experienced hypoglycemia (12.8 vs. 3.7%; P = 0.024) and genital infections (5.5 vs. 0%; P = 0.029). Events of urinary tract infection were reported by 6.4% of patients in both groups. CONCLUSIONS:Dapagliflozin was well tolerated and effective over 24 weeks as add-on to metformin plus sulfonylurea. Adverse effects included hypoglycemia and genital infections.
RCT Entities:
OBJECTIVE: To evaluate the efficacy and safety of dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin and sulfonylurea. RESEARCH DESIGN AND METHODS: Patients with HbA1c of 7.0% (53 mmol/mol) to 10.5% (91 mmol/mol) receiving sulfonylurea and metformin were randomized to receive dapagliflozin 10 mg/day (n = 109) or placebo (n = 109) for 24 weeks. RESULTS: HbA1c (baseline: dapagliflozin 8.08% [65 mmol/mol]; placebo 8.24% [67 mmol/mol]) and fasting plasma glucose (baseline: dapagliflozin 167.4 mg/dL [9.29 mmol/L]; placebo 180.5 mg/dL [10.02 mmol/L]) significantly improved from baseline with dapagliflozin (placebo-subtracted change -0.69% [-7.5 mmol/mol], P < 0.0001; -33.5 mg/dL [-1.86 mmol/L], P < 0.0001, respectively). More patients achieved a therapeutic glycemic response (HbA1c <7.0% [53 mmol/mol]) with dapagliflozin (31.8%) versus placebo (11.1%) (P < 0.0001). Body weight and systolic blood pressure were significantly reduced from baseline over 24 and 8 weeks, respectively, with dapagliflozin (placebo-subtracted change -2.1 kg, P < 0.0001; -3.8 mmHg, P = 0.0250). Patients receiving dapagliflozin showed placebo-subtracted increases in total, LDL, and HDL cholesterol (11.4 mg/dL, P = 0.0091; 11.4 mg/dL, P = 0.0030; 2.2 mg/dL, P = 0.0172, respectively) with no change in LDL/HDL cholesterol ratio (0.1; P = 0.2008) or triglycerides (-16.5 mg/dL; P = 0.1755). Adverse events occurred in 48.6% of patients receiving dapagliflozin and 51.4% receiving placebo. Significantly more patients with dapagliflozin compared with placebo experienced hypoglycemia (12.8 vs. 3.7%; P = 0.024) and genital infections (5.5 vs. 0%; P = 0.029). Events of urinary tract infection were reported by 6.4% of patients in both groups. CONCLUSIONS:Dapagliflozin was well tolerated and effective over 24 weeks as add-on to metformin plus sulfonylurea. Adverse effects included hypoglycemia and genital infections.
Authors: Abdullah Kaplan; Emna Abidi; Ahmed El-Yazbi; Ali Eid; George W Booz; Fouad A Zouein Journal: Heart Fail Rev Date: 2018-05 Impact factor: 4.214
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