From the Guidelines
Dapagliflozin is recommended for patients with type 2 diabetes due to its significant cardiovascular benefits, particularly in reducing the risk of hospitalization for heart failure and cardiovascular death, as demonstrated in the DECLARE-TIMI 58 study 1. The DECLARE-TIMI 58 study, a large cardiovascular outcome trial, showed that dapagliflozin 10 mg once daily reduced the risk of hospitalization for heart failure and cardiovascular death by 17% in patients with established or at high risk for cardiovascular disease 1.
Key Findings
- Dapagliflozin did not significantly reduce major adverse cardiovascular events (MACE) compared to placebo, but demonstrated a significant reduction in the composite of cardiovascular death or hospitalization for heart failure 1.
- The study included over 17,000 patients followed for a median of 4.2 years, making it one of the largest cardiovascular outcome trials for SGLT2 inhibitors 1.
- Dapagliflozin showed renal protective effects, reducing the progression of kidney disease 1.
Benefits and Side Effects
- Common side effects included genital infections and diabetic ketoacidosis, though these were relatively rare 1.
- The findings suggest that dapagliflozin should be considered in the management of type 2 diabetes patients with cardiovascular risk factors, especially those with heart failure or kidney disease, as it provides benefits beyond glucose control by addressing cardiovascular and renal outcomes 1.
Patient Selection
- Dapagliflozin may be particularly beneficial for patients with established atherosclerotic cardiovascular disease or multiple risk factors 1.
- The study's results are consistent with those of other SGLT2 inhibitors, such as empagliflozin, which have also shown significant cardiovascular benefits in patients with type 2 diabetes 1.
From the FDA Drug Label
The Dapagliflozin Effect on Cardiovascular Events (DECLARE, NCT01730534) was an international, multicenter, randomized, double-blind, placebo-controlled, clinical trial conducted to determine the effect of dapagliflozin relative to placebo on cardiovascular (CV) outcomes when added to current background therapy
The incidence rate of MACE was similar in both treatment arms: 2.30 MACE events per 100 patient-years on dapagliflozin vs 2.46 MACE events per 100 patient-years on placebo.
Dapagliflozin was superior to placebo in reducing the incidence of the primary composite endpoint of hospitalization for heart failure or CV death [HR 0.83 (95% CI 0.73,0.95)].
The DECLARE-TIMI 58 study 2 showed that dapagliflozin had a similar incidence rate of major adverse cardiovascular events (MACE) compared to placebo. However, dapagliflozin was superior to placebo in reducing the incidence of hospitalization for heart failure or cardiovascular death, with a hazard ratio (HR) of 0.83. The treatment effect was primarily due to a significant reduction in the risk of hospitalization for heart failure.
- Key findings:
- Similar incidence rate of MACE between dapagliflozin and placebo
- Dapagliflozin reduced the incidence of hospitalization for heart failure or CV death
- Hazard ratio for hospitalization for heart failure or CV death: 0.83 (95% CI 0.73,0.95)
- Study population: Adults with type 2 diabetes mellitus and established CV disease or two or more additional CV risk factors.
From the Research
Study Overview
- The Declare Timi 58 study, also known as the Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58, is a phase 3b randomized, double-blind, placebo-controlled trial designed to evaluate the cardiovascular safety and efficacy of dapagliflozin 3.
- The study included 17,160 patients with type 2 diabetes mellitus and either established atherosclerotic cardiovascular disease or multiple risk factors for atherosclerotic cardiovascular disease.
Primary Outcomes
- The primary safety outcome of the study was the time to the first event of the composite of cardiovascular death, myocardial infarction, or ischemic stroke (major adverse cardiovascular events; MACEs) 3.
- The co-primary efficacy outcomes were the composite of cardiovascular death, myocardial infarction, or ischemic stroke and the composite of cardiovascular death or hospitalization for heart failure.
Results
- Dapagliflozin reduced the relative risk of MACE by 16% and the absolute risk by 2.6% in patients with previous myocardial infarction (n=3584), whereas there was no effect in patients without previous myocardial infarction 4.
- The beneficial effects of dapagliflozin on hospitalization for heart failure and renal outcomes were consistent across all baseline systolic blood pressure categories, with no evidence of modification of treatment effect 5.
- Dapagliflozin was associated with a 21% lower risk of hospitalization for heart failure or cardiovascular mortality versus other glucose-lowering drugs in a real-world population similar to those included in the DECLARE-TIMI 58 study 6.
Cost-Effectiveness
- Empagliflozin, another SGLT-2 inhibitor, was found to be more cost-effective than dapagliflozin, canagliflozin, or standard of care in patients with type 2 diabetes and established cardiovascular disease, mainly due to its direct reduction in cardiovascular death 7.
Key Findings
- Dapagliflozin provides cardiorenal benefits in patients with type 2 diabetes at high atherosclerotic cardiovascular disease risk, independent of baseline blood pressure 5.
- The study suggests that patients with type 2 diabetes and previous myocardial infarction may derive greater benefit from dapagliflozin therapy 4.
- Dapagliflozin was safe with regard to cardiovascular outcomes and resulted in lower event rates of hospitalization for heart failure and cardiovascular mortality versus other glucose-lowering drugs in a real-world population 6.