SGLT2 Inhibitors Reduce Cardiovascular Deaths, Despite Diabetes


Many patients with heart failure do not receive optimal therapy until they present to a hospital with exacerbations.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors such as dapagliflozin (Farxiga) and empagliflozin (Jardiance) reduce hospitalizations and may reduce cardiovascular deaths in patients with heart failure regardless of the presence of diabetes, according to new research.

Results of a meta-analysis of randomized control trials (RCTs), published in the Annals of Internal Medicine,1 support existing guidelines that recommend SGLT2 inhibitors for preventing incident and worsening heart failure in people with type 2 diabetes, heart failure, or both, the American College of Physicians (ACP) said in a news release.2

Many patients with heart failure do not receive optimal therapy until they present to a hospital with exacerbations, and patients who receive a diagnosis in the hospital have a twofold increased risk of death and recurrent hospitalization, ACP said.

Previous randomized trials have shown that SGLT2 inhibitors reduce the risks of hospitalization for heart failure and cardiovascular death for people with diabetes. Other trials have also shown that these benefits may extend to patients with heart failure but without diabetes, ACP noted.

Researchers from Sichuan University in Chengdu, China conducted a systemic review and meta-analysis of 8 RCTs with more than 15,000 participants. They evaluated the effect of dapagliflozin, empagliflozin, or canagliflozin (Invokana) in patients with heart failure, regardless of the presence of type 2 diabetes.

The authors found that in patients with heart failure—both those with preserved and those with reduced ejection fraction and regardless of the presence of diabetes—SGLT2 inhibitors demonstrated relative benefits in reducing hospitalizations for heart failure and cardiovascular death with high to moderate certainty.

However, the authors warn that these reductions were associated with increasing rates of genital infections.

“The amount of potential benefit of SGLT2 inhibitors is determined by both the relative benefit for heart failure hospitalizations and the patient's baseline risk and the relative benefits of SGLT2 inhibitors for reducing heart failure hospitalizations may be greatest within the first year and may attenuate later,” ACP said.


  1. Zou X, Qingyang S, Vandvik PO, et al. Sodium-glucose cotransporter-2 inhibitors in patients with heart failure: A systematic review and meta-analysis. Ann Intern Med. Published online April 12, 2022. doi:10.7326/M21-4284
  2. SGLT2 inhibitors reduce hospitalization for heart failure regardless of presence of diabetes. News release. American College of Physicians. April 11, 2022. Accessed May 2, 2022.
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