Use of Sodium-Glucose Cotransporter-2 Inhibitors in Clinical Practice for Heart Failure Prevention and Treatment: Beyond Type 2 Diabetes. A Narrative Review

Adv Ther. 2022 Feb;39(2):845-861. doi: 10.1007/s12325-021-01989-z. Epub 2021 Dec 9.

Abstract

Despite the availability of established treatments, heart failure (HF) is associated with a poor prognosis and its management is suboptimal, highlighting the need for new options for treatment and prevention. Patients with type 2 diabetes (T2D) often experience cardiovascular (CV) complications, with HF being one of the most frequent. Consequently, several CV outcome trials have focused on glucose-lowering therapies and their impact on CV outcomes. An established treatment for T2D, sodium-glucose cotransporter-2 inhibitors (SGLT-2is; canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) have demonstrated beneficial effects on CV outcomes in long-term studies of patients with T2D with established CV disease and/or a broad range of CV risk factors. Recent studies have extended these findings to patients with HF, with and without T2D, finding that SGLT-2is (particularly dapagliflozin and empagliflozin) are effective therapeutic interventions for the treatment and prevention of HF. This narrative review article discusses the use of SGLT-2is in the treatment and prevention of HF in patients with and without T2D. Dapagliflozin was the first SGLT-2i to receive US Food and Drug Administration (FDA) approval for treatment of HF, to reduce the risk of CV death and hospitalization for HF in adults with HF with reduced ejection fraction (HFrEF) with and without T2D. Recently, the FDA also approved empagliflozin for this indication. Given the new HFrEF indications for dapagliflozin and empagliflozin, and the likelihood of similar approvals for other SGLT-2is, cardiology guidelines are beginning to integrate SGLT-2is into a standard-of-care treatment regimen for patients with HFrEF. The utility of SGLT-2is in HF with preserved EF (HFpEF) shows promise based on data from the EMPEROR-Preserved study of empagliflozin in patients with HFpEF. Further clinical trial evidence may lead to more widespread use and further integration of SGLT-2is into standard-of-care regimens for the treatment and management of HF in patients with and without T2D.

Keywords: Canagliflozin; Cardiovascular; Dapagliflozin; Empagliflozin; Ertugliflozin; Heart failure; Sodium-glucose cotransporter 2 inhibitor; Sotagliflozin; Type 2 diabetes.

Plain language summary

Heart failure is a medical condition in which the heart cannot pump enough blood. Several types of drugs have been used to treat heart failure, but these may not work for every patient, and heart failure can get worse over time even with treatment. That is why new drugs are needed to treat and prevent heart failure. People with diabetes (type 2 diabetes) often have other conditions related to the heart (cardiovascular system), heart failure being one of the most common. Because of this, there have been studies (clinical trials) in people with diabetes to see if diabetes drugs can also treat and/or reduce the risk of cardiovascular disease. In clinical trials, a type of diabetes drug, sodium-glucose cotransporter-2 inhibitors (SGLT-2is, including canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), has helped people with both diabetes and cardiovascular disease. Recent clinical trials of dapagliflozin and empagliflozin showed they were effective for treating and preventing heart failure in people without diabetes as well as in those with diabetes. Based on these studies, the US Food and Drug Administration approved dapagliflozin and empagliflozin for heart failure in patients with or without diabetes. These drugs can be prescribed for adults with or without diabetes to treat and prevent a type of heart failure, heart failure with reduced ejection fraction, in which the heart is too weak to pump enough blood to the body. Several clinical studies are ongoing that will provide more information about these drugs, SGLT-2is, which will help healthcare providers to treat people with heart failure.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucose
  • Heart Failure* / complications
  • Heart Failure* / drug therapy
  • Heart Failure* / prevention & control
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Sodium / therapeutic use
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Stroke Volume

Substances

  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sodium
  • Glucose