Dapagliflozin’s Effects on Glycemia and Cardiovascular Risk Factors in High-Risk Patients With Type 2 Diabetes: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With a 28-Week Extension

• DOI: 10.2337/dc14-0315
• Publication Date: 2015-04-08T04:40:08Z
• Authors: William T. Cefalu; Lawrence A. Leiter; Tjerk W.A. de Bruin; Ingrid Gause-Nilsson; Jennifer Sugg; Shamik J. Parikh
• Keywords: Blood Glucose; Male; Blood Pressure; 03 medical and health sciences; 0302 clinical medicine; Double-Blind Method; Glucosides; Risk Factors; Humans; Hypoglycemic Agents; Insulin; Benzhydryl Compounds; Glycated Hemoglobin; Analysis of Variance; Body Weight; Clinical Care/Education/Nutrition/Psychosocial Research; Middle Aged; Hypoglycemia; 3. Good health; Treatment Outcome; Diabetes Mellitus, Type 2; Urinary Tract Infections; Female; Diabetic Angiopathies

OBJECTIVE To assess the efficacy and safety of dapagliflozin, a selective sodium-glucose cotransporter 2 inhibitor, compared with placebo in patients with type 2 diabetes (T2D), documented pre-existing cardiovascular disease (CVD), and a history of hypertension.

RESEARCH DESIGN AND METHODS Patients (N = 922) were randomized to receive 10 mg dapagliflozin or placebo in a double-blind trial for 24 weeks, followed by a 28-week extension period. In patients receiving insulin, the insulin dose was reduced by 25% at randomization. Patients were stratified by age, insulin use, and time from the most recent qualifying cardiovascular (CV) event. Co-primary end points were a change from baseline in hemoglobin A1c (HbA1c) and the proportion of patients achieving a combined reduction in HbA1c of ≥0.5% (5.5 mmol/mol), body weight (BW) of ≥3%, and systolic blood pressure (SBP) of ≥3 mmHg.

RESULTS At 24 weeks, dapagliflozin significantly reduced HbA1c (−0.38% [−4.2 mmol/mol]) from baseline (8.18%) compared with a slight increase with placebo from baseline (8.08%) (0.08% [0.9 mmol/mol]). Significantly more patients met the three-item end point with treatment with dapagliflozin than with placebo (11.7% vs. 0.9%, respectively). Changes were maintained over 52 weeks. Although ∼42% of patients were ≥65 years old, similar results were observed in both age-stratified groups. Serious adverse events, hypoglycemia, urinary tract infections, and cardiac disorders were similar between groups. Adverse events of hypotension, dehydration, hypovolemia, genital infection, and renal failure or impairment occurred more often with dapagliflozin treatment.

CONCLUSIONS In this study that evaluated T2D patients who were at high risk for future CVD events, dapagliflozin administration had significantly greater effects in reducing HbA1c, BW, and SBP, without adversely impacting CV safety when compared with placebo treatment.