22. Long-Term Safety and Efficacy of Dapagliflozin in Patients with T2DM and Cardiovascular Disease (106-OR)

Given the high risk of cardiovascular disease (CVD) in patients (pts) with T2DM, it is important to assess the efficacy and safety of antihyperglycemic agents in this population. This study reports pooled data from 2 phase 3 studies (NCT01031680, NCT01042977) in pts with T2DM and CVD treated with 10 mg/d DAPA (n = 284) or placebo (PBO) (n = 284) who entered the 2 year follow-up period. Baseline characteristics, including CVD characteristics, were similar between the treatment groups. The mean age was 63 years (38% ≥ 65-75, 6% ≥ 75 years) and the mean duration of T2DM was 12 years. At 104 weeks pts receiving DAPA vs. PBO had a greater reduction in HbA1c -0.35% (95% CI; -0.59, -0.12), body weight (BW) -3.16 kg (95% CI; -3.95, -2.38) and SBP -2.03 mmHg (95% CI; -4.10, 0.04). Pts receiving DAPA had a better predefined 3-item end point of clinical benefit (change from baseline in absolute drop of ≥ 0.5% HbA1c, relative drop of ≥ 3% BW, absolute drop of ≥ 3 mm Hg SBP) from week 24 (9.5% vs. 2.1%) to week 52 (10.9% vs. 3.5%) and week 104 (6.7% vs. 1.4%), respectively. Pts receiving DAPA experienced more genital infections and urinary tract infections vs. PBO; hypoglycemia, renal impairment/failure and volume depletion were balanced between groups. The efficacy of DAPA in reducing HbA1c, SBP and BW over 2 years together with its safety profile makes DAPA appropriate for use in a highrisk population of pts with T2DM and CVD. Placebo (n = 284) Dapagliflozin (n = 284) ≥ 1 AE, n (%) 220 (77.5) 237 (83.5) ≥ 1 SAE, n (%) 63 (22.2) 74 (26.1) AE leading to discontinuation, n (%) 21 (7.4) 11 (3.9) Hypoglycemia, n (%) 109 (38.4) 106 (37.3) AEs of special interest, n (%) Genital infection 1 (0.4) 19 (6.7) Urinary tract infection 18 (6.3) 26 (9.2) Renal impairment/failure 18 (6.3) 15 (5.3) Volume depletion 8 (2.8) 7 (2.5) Adjusted change from baseline HbA1c, %, mean (95% CI) 24 week 0.13 (0.03, 0.24) -0.36 (-0.45, -0.26) 52 week 0.03 (-0.09, 0.14) -0.44 (-0.54, -0.34) 104 week -0.01 (-0.20, 0.18) -0.36 (-0.51, -0.22) Adjusted change from baseline seated SBP, mm Hg, mean (95% CI) 24 week -1.13 (-2.33, 0.07) -3.38 (-4.59, -2.16) 52 week -0.63 (-2.03, 0.77) -2.61 (-4.02, -1.19) 104 week -0.05 (-1.53, 1.43) -2.08 (-3.53, -0.64) Adjusted change in body weight, kg, mean (95% CI) 24 week -0.05 (-0.41, 0.31) -2.24 (-2.61, -1.88) 52 week -0.15 (-0.60, 0.31) -2.57 (-3.03, -2.12) 104 week 0.11 (-0.45, 0.67) -3.05 (-3.60, -2.50) AE, adverse events; SAE, serious AE (Table).