In Patients with Cancer and Diabetes, SGLT2 Inhibitors Could Provide Cardioprotection Against Anthracyclines

An analysis of more than 3000 patients with cancer and diabetes suggests SGLT2 inhibitor use may provide a cardioprotective benefit among patients treated with anthracyclines.

As the field of cardiooncology continues to evolve, results of the study, which indicate patients treated with SGLT2 inhibitors experienced a lower rate of cardiovascular events than their counterparts without SGLT2 inhibitor use, support further research into the topic.

“The use of SGLT2 inhibitors was associated with a lower rate of cardiac events after anthracycline therapy in patients with cancer and DM. To our knowledge, these findings are the first data associating SGLT2 inhibitors with improved cardiac and noncardiac outcomes in this population,” wrote investigators.

Conducted by investigators from Massachusetts General Hospital, Brigham and Women’s Hospital, and Harvard Medical School, the present analysis was designed as a retrospective cohort study of patients with diabetes and cancer treated with anthracyclines in the Massachusetts General Brigham system prior to September 2020. From a cohort of 3033 patients with diabetes and cancer who were total of 1902 patients with a diabetes diagnosis coded prior to anthracycline initiation for inclusion. Of these, 87 patients were treated with SGLT2 inhibitors, but only 32 received SGLT2 inhibitors during anthracycline treatment initiation.

For the purpose of analysis, these 32 individuals served as cases and were matched in a 3:1 ratio based on age, gender, and year of anthracycline treatment to patients within the 1807 patients with a diabetes diagnosis coded prior to anthracycline initiation. As a result, the analysis included 32 cases and 96 controls. The primary cardiovascular outcome of interest was a composite of cardiovascular events that included heart failure incidence, heart failure admissions, new cardiomyopathy, and clinically significant arrhythmias. The primary safety outcome of interest was incidence of overall mortality.

Upon analysis, investigators identified a total of 20 primary outcome events during a follow-up period lasting a median of 1.5 years. Results of the investigators’ analyses indicated incidence of cardiovascular events was lower among case patients than their counterparts in the control group, with rates of 3% and 20%, respectively (P=.025). Analysis of the primary safety outcome indicated patients in the control groups had a lower mortality rate than those in the control group (9% vs 43%; P <.001) as well as a lower composite of sepsis and neutropenic fever (16% vs 40%; P=.013).

In an editorial comment published in JACC: Heart Failure, Michel Khouri, MD, and Stephen Greene, MD, both of Duke Health, explored the present data, discuss what it adds to the current evidence base, and how it helps inform future research into the potential cardioprotection provided by SGLT2 inhibitors to patients with diabetes and cancer. With an interest in taking a deep dive on the topic, PracticalCardiology reached out to Greene for further insight into the study and its implications.

“It did generate the hypothesis that SGLT2 inhibitors might be helpful for heart failure prevention and for death prevention among patients receiving anthracyclines who have diabetes. The issue with all these observational studies is, despite the rigorous statistical methods, there is always chance for confounding and unmeasured or residual confounding. I think when you saw the magnitude of risk reduction in that association seen in this study, it does suggest there might be some confounding going on, but needless to say, biologically we have seen in the randomized clinical trial data of patients with diabetes that SGLT2 inhibitors consistently prevent incident heart failure,” Greene explained. “So, you might ask yourself, “Well, if they can prevent incident heart failure in an at-risk population with diabetes, can they prevent nuance at heart failure in an at-risk population getting a potentially cardiotoxic therapy like anthracyclines, maybe with or without diabetes concurrently?”, but I think we will need a randomized clinical trial to definitively support use of SGLT2 inhibitors for cardioprotection among people receiving anthracyclines.”

This study, “Sodium-Glucose Co-Transporter-2 Inhibitors and Cardiac Outcomes Among Patients Treated With Anthracyclines,” was published in JACC Heart Failure.