Cardiovascular, Renal, and Metabolic Outcomes of Dapagliflozin Versus Placebo in a Primary Cardiovascular Prevention Cohort: Analyses From DECLARE-TIMI 58
Open Access
- 2 March 2021
- journal article
- research article
- Published by American Diabetes Association in Diabetes Care
- Vol. 44 (5), 1159-1167
- https://doi.org/10.2337/dc20-2492
Abstract
International guidelines propose prescribing sodium–glucose cotransporter 2 (SGLT2) inhibitors to patients with type 2 diabetes (T2D) as secondary prevention in patients with established atherosclerotic cardiovascular disease (ASCVD) or for primary prevention of cardiovascular events in high-risk patients with multiple risk factors (MRF) for ASCVD. The current analyses expand on the cardiovascular renal and metabolic effects of SGLT2 inhibitors in MRF patients. In DECLARE-TIMI 58, 17,160 patients with T2D and MRF (59.4%) or established ASCVD (40.6%) were randomized to dapagliflozin versus placebo; patients were followed for a median of 4.2 years. The cardiovascular and renal outcomes in the MRF cohort were studied across clinically relevant subgroups for treatment effect and subgroup-based treatment interaction. Among patients with MRF, the reduction with dapagliflozin in risk of cardiovascular death or hospitalization for heart failure (CVD/HHF) (hazard ratio [HR] 0.84, 95% CI 0.67–1.04) and the renal-specific outcome (HR 0.51, 95% CI 0.37–0.69) did not differ from that for patients with ASCVD (Pinteraction 0.99 and 0.72, respectively). The effect on CVD/HHF was entirely driven by a reduction in HHF (HR 0.64, 95% CI 0.46–0.88). The benefits of dapagliflozin on HHF and on the renal-specific outcome, among the subset with MRF, were directionally consistent across clinically relevant subgroups. At 48 months, HbA1c, weight, systolic blood pressure, and urinary albumin–to–creatinine ratio were lower with dapagliflozin versus placebo and estimated glomerular filtration rate was higher (P < 0.001). In patients with T2D and MRF, dapagliflozin reduced the risk of HHF and adverse renal outcomes regardless of baseline characteristics. These analyses support the benefit of dapagliflozin for important outcomes in a broad primary prevention population.Keywords
Funding Information
- AstraZeneca
This publication has 35 references indexed in Scilit:
- Canagliflozin and Cardiovascular and Renal Events in Type 2 DiabetesThe New England Journal of Medicine, 2017
- Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trialsThe Lancet Diabetes & Endocrinology, 2017
- Empagliflozin and Progression of Kidney Disease in Type 2 DiabetesThe New England Journal of Medicine, 2016
- Heart Failure Considerations of Antihyperglycemic Medications for Type 2 DiabetesCirculation Research, 2016
- Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 DiabetesThe New England Journal of Medicine, 2015
- Pharmacodynamics, Efficacy and Safety of Sodium–Glucose Co-Transporter Type 2 (SGLT2) Inhibitors for the Treatment of Type 2 Diabetes MellitusDrugs, 2014
- Kidney Disease and Increased Mortality Risk in Type 2 DiabetesJournal of the American Society of Nephrology, 2013
- Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trialsThe Lancet, 2009
- 10-Year Follow-up of Intensive Glucose Control in Type 2 DiabetesThe New England Journal of Medicine, 2008
- Effect of a Multifactorial Intervention on Mortality in Type 2 DiabetesThe New England Journal of Medicine, 2008