By Ana Gajic


Dr. David Mazer
Dr. David Mazer

A study led by St. Michael’s Hospital set out to discover why a certain class of diabetes medication has been perceived to have a positive impact on heart health.

Published in Circulation and presented at the American Heart Association Scientific Sessions last month, this research was part of the EMPA-HEART CardioLink-6 randomized controlled trial assessing the impact of a diabetes drug – empagliflozin – on left ventricular mass in patients with type 2 diabetes and coronary artery disease.

Dr. David Mazer, a scientist at the Keenan Research Centre for Biomedical Science, sat down with us to tell us more about this work.

Q. What were you hoping to learn with this research?

Recent evidence has demonstrated that the sodium-glucose transport protein 2 (SGLT2) inhibitor class of drugs improves negative heart health outcomes, such as death from heart-related causes, hospital admission for heart failure, heart attack, or stroke, in patients with diabetes with heart disease or heart failure.

Hemoglobin is the protein in red blood cells that delivers oxygen to the tissues, and hemocrit measures the volume of red blood cells compared to the total blood volume. A consistent rise in both of these levels has been observed in patients on SGLT2 inhibitors.

It has been suggested that this rise in hemoglobin may be the primary reason for the observed beneficial reduction in poor outcomes related to heart health.

The reason behind for this increase in hemoglobin or hematocrit was not known, so we conducted this study to determine whether this observed effect was due to stimulation of the production of red blood cells by a hormone called erythropoietin, which is naturally produced in the kidney. This process is also known as erythropoietin-mediated erythropoiesis.

Q. Why were you and your team interested in this particular topic of heart health among patients with diabetes?

More than three million Canadians have type 2 diabetes. Furthermore, approximately 30 per cent of these people also have cardiovascular disease. We regularly come across such patients with type 2 diabetes with cardiovascular disease at our institution.

It is important for us to better understand how treatments that patients may be receiving work so that we can further improve therapeutic strategies and outcomes for these patients.

Q. What were the key findings of your study?

We observed an early rise in erythropoietin levels in patients treated with empagliflozin – an SGLT2 inhibitor that is used to treat diabetes – relative to those not treated with the diabetes medication.

Six months of this treatment was associated with an increase in hematocrit and hemoglobin levels, and changes to red blood cell amounts and iron levels.

Q. Why is this observed increase in levels important?

We provide convincing evidence to suggest that these drugs stimulate the bone marrow to produce more red blood cells via an early increase in the hormone erythropoietin in people with diabetes.

The increase in red blood cells may help carry more oxygen to the heart and body. These findings enhance our understanding of the mechanism by which SGLT2 inhibitors can improve heart failure and other cardiovascular outcomes.

Q. What’s next for this research?

This study was part of our EMPA-HEART CardioLink-6 randomized controlled trial assessing the impact of empagliflozin on left ventricular mass in patients with type 2 diabetes and coronary artery disease.

Another very recent study showed that these drugs may also improve cardiovascular outcomes in patients without diabetes, so we are planning to do a similar study in people without diabetes to see if these beneficial effects extend to those patients as well.


This trial was supported by an unrestricted investigator-initiated study grant from the biopharmaceutical company, Boehringer Ingelheim, which manufactures empagliflozin. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation or decision to submit the manuscript for publication.

This story is one of many we’re highlighting to share discoveries led by our Keenan Research Centre for Biomedical Science. The Keenan is home to basic science and translational research at Unity Health. Our researchers target common and high burden illnesses that are important to patients and strive to make discoveries that will improve patients’ lives. The Keenan: Driven by discovery. Share our stories using #TheKeenanDiscovery.

About St. Michael’s Hospital

St. Michael’s Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in more than 27 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, care of the homeless and global health are among the Hospital’s recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Centre, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael’s Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto.

About Unity Health Toronto

Unity Health Toronto, comprised of Providence Healthcare, St. Joseph’s Health Centre and St. Michael’s Hospital, works to advance the health of everyone in our urban communities and beyond. Our health network serves patients, residents and clients across the full spectrum of care, spanning primary care, secondary community care, tertiary and quaternary care services to post-acute through rehabilitation, palliative care and long-term care, while investing in world-class research and education. For more information, visit www.unityhealth.to.