L A Leiter1, W T Cefalu2, T W A de Bruin3, J Xu4, S Parikh5, E Johnsson6, I Gause-Nilsson6. 1. Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St Michael's Hospital, University of Toronto, Toronto, ON, Canada. 2. Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA. 3. Research & Development, AstraZeneca, Gaithersburg, MD, USA. 4. Biometrics and Informatics, AstraZeneca, Gaithersburg, MD, USA. 5. Global Medical Affairs-CV and Metabolism, AstraZeneca, Gaithersburg, MD, USA. 6. Research & Development, AstraZeneca Gothenburg, Mölndal, Sweden.
Abstract
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 (NCT01031680 and NCT01042977) in high-risk patients (N = 1887) with T2DM and CVD treated withdapagliflozin (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.
RCT Entities:
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 (NCT01031680 and NCT01042977) 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.
Authors: Alicia Swee Yan Yip; Shariel Leong; Yao Hao Teo; Yao Neng Teo; Nicholas L X Syn; Ray Meng See; Caitlin Fern Wee; Elliot Yeung Chong; Chi-Hang Lee; Mark Y Chan; Tiong-Cheng Yeo; Raymond C C Wong; Ping Chai; Ching-Hui Sia Journal: Ther Adv Chronic Dis Date: 2022-03-23 Impact factor: 5.091
Authors: Kathryn S Taylor; Julie Mclellan; Jan Y Verbakel; Jeffrey K Aronson; Daniel S Lasserson; Nicola Pidduck; Nia Roberts; Susannah Fleming; Christopher A O'Callaghan; Clare R Bankhead; Amitava Banerjee; Fd Richard Hobbs; Rafael Perera Journal: BMJ Open Date: 2019-09-20 Impact factor: 2.692