We know that a class of diabetes medications called SGLT2 inhibitors prevent heart failure in people with type 2 diabetes. We also know that these medications have multiple mechanisms of action beyond just lowering blood sugars.
The questions have therefore been asked:
Can SGLT2 inhibitors treat people with established heart failure?
Can SGLT2 inhibitors be used to treat heart failure in people who don’t have diabetes?
The DAPA-HF study, which was presented just days ago at the European Society of Cardiology meeting, enrolled 4,744 people with heart failure (55% of whom did not have diabetes), and randomized them to receive either dapagliflozin (Forxiga) 10mg or placebo. The primary endpoint was a combination of cardiovascular death or a worsening heart failure event (defined as an unplanned heart failure hospitalization, or an urgent heart failure visit requiring intravenous treatment). These people were very well treated with existing heart failure treatments prior to, and during, the trial.
They found that after a median treatment duration of just 18 months, dapagliflozin reduced cardiovascular death and heart failure events by 26% (16.3% of people on dapagliflozin vs 21.2% of people on placebo). Stated another way – if 21 people were treated for 18 months, one cardiovascular death or heart failure event would be prevented. Cardiovascular death was reduced by 18% (9.6% of people in the dapagliflozin group vs 11.5% of people in the placebo group), and heart failure events were reduced by 30% (10% of people in the dapagliflozin group vs 13.7% of people in the placebo group). Death from any cause was also reduced by 17%. Importantly, people without type 2 diabetes enjoyed a similar benefit to those who did have type 2 diabetes. Dapagliflozin was well tolerated without any new side effect concerns.
The DAPA-HF study is a landmark trial, as it is the first study to show that an SGLT2 inhibitor can benefit people with heart failure, whether or not they have type 2 diabetes. The SGLT2 inhibitors empagloflozin (Jardiance) and canagliflozin (Invokana) both have data to support that they are of benefit in preventing heart failure in people with type 2 diabetes. Empagliflozin is currently also being studied as a treatment of heart failure in people with and without type 2 diabetes.
Disclaimer: I receive honoraria as a continuing medical education speaker and consultant from the makers of dapagliflozin (Astra Zeneca), empagliflozin (Boehringer Ingelheim/Eli Lilly), and canagliflozin (Janssen). I have been involved as an investigator in clinical trials of SGLT2 inhibitors.
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