- Question
- Is the SGLT2 inhibitor dapagliflozin cardiovascularly safe in patients with type 2 diabetes who have or are at risk for atherosclerotic cardiovascular disease, and does it reduce cardiovascular events?
- Design
- Multicenter, randomized, double-blind, placebo-controlled phase 3 trial that evaluated 17160 patients with a median follow-up of 4.2 years.
- Population
- Patients with type 2 diabetes who had established atherosclerotic cardiovascular disease or were at risk for it; 10186 of them did not have atherosclerotic cardiovascular disease.
- Intervention
- Dapagliflozin 10 mg once daily on top of standard care for diabetes, comorbidities and cardiovascular risk factors.
- Control
- Placebo on top of the same standard care.
- Primary outcome
- The primary safety outcome was major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction or ischemic stroke). The primary efficacy outcomes were MACE and the composite of cardiovascular death or hospitalization for heart failure.
- Results
- Dapagliflozin met the noninferiority criterion versus placebo for MACE (upper boundary of the 95% CI <1.3; P<0.001 for noninferiority) but did not lower MACE (8.8% vs. 9.4%; HR 0.93; 95% CI, 0.84 to 1.03; P=0.17). It did lower cardiovascular death or hospitalization for heart failure (4.9% vs. 5.8%; HR 0.83; 95% CI, 0.73 to 0.95; P=0.005), driven by fewer hospitalizations for heart failure (HR 0.73; 95% CI, 0.61 to 0.88), with no difference in cardiovascular death (HR 0.98; 95% CI, 0.82 to 1.17). The renal composite was lower with dapagliflozin (4.3% vs. 5.6%; HR 0.76; 95% CI, 0.67 to 0.87).
- Safety
- Diabetic ketoacidosis was more common with dapagliflozin than placebo (0.3% vs. 0.1%; P=0.02), as were genital infections that were serious or led to discontinuation (0.9% vs. 0.1%; P<0.001).
- Conclusion
- In patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease, dapagliflozin neither increased nor reduced MACE versus placebo, but lowered cardiovascular death or hospitalization for heart failure, reflecting fewer heart failure hospitalizations.
- Why it matters
- It established the cardiovascular safety of dapagliflozin and added a heart failure and renal benefit in a broad type 2 diabetes population, including patients without established atherosclerotic disease, fueling interest in this drug class beyond glycemic control.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 14, 2026