Long‐term maintenance of efficacy of dapagliflozin in patients with type 2 diabetes mellitus and cardiovascular disease

Aim To evaluate the long‐term efficacy, safety and tolerability of dapagliflozin versus placebo added to usual care in patients with type 2 diabetes mellitus ( T2DM ) and cardiovascular disease ( CVD ). Methods Data were pooled from two phase III studies ( NCT 01031680 and NCT 01042977) in high‐risk patients (N = 1887) with T2DM and CVD treated with dapagliflozin (10 mg/day) or placebo. Patients completing the double‐blind treatment studies (24 weeks) entered one or two sequential double‐blind, long‐term ( LT ) extensions of 28 ( LT1 ; n = 1649) and 52 ( LT2 ; n = 568) weeks. Results Baseline and CVD characteristics were similar in the two groups. Patients entering LT1 and LT2 on dapagliflozin maintained a greater mean reduction in glycated haemoglobin ( HbA1c ) versus placebo at 52 weeks [ LT1 , −0.58% (95% confidence interval −0.68, −0.49)] and 104 weeks [ LT2 , −0.35% (95% confidence interval −0.59, −0.12)]. Mean body weight and systolic blood pressure ( SBP ) reductions versus placebo were maintained in patients entering LT1 (52 weeks; −2.23 kg and −3.25 mmHg, respectively) and LT2 (104 weeks; −3.16 kg and −2.03 mmHg, respectively). Patients on dapagliflozin had a better three‐item composite endpoint of clinical benefit (glycaemia, weight and SBP ) compared with placebo at week 24 ( LT1 , 10.1% vs. 1.1%) and week 104 ( LT2 , 6.7% vs. 1.4%). Genital and urinary tract infections were more frequent with dapagliflozin than with placebo. Events of hypoglycaemia, renal impairment/failure and volume depletion were similar between groups. Conclusions The long‐term efficacy of dapagliflozin to maintain reductions in HbA1c , SBP and body weight over 2 years, together with its tolerability profile, make dapagliflozin an appropriate option in high‐risk patients with T2DM and CVD .