Author + information
- Received January 22, 2020
- Revision received February 5, 2020
- Accepted February 5, 2020
- Published online June 22, 2020.
- aCardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada
- bDivision of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada
- ↵∗Address for correspondence:
Dr. Gary D. Lopaschuk, Cardiovascular Research Centre, 423 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
• Treatment with SGLT2 inhibitors reduces the incidence of cardiovascular death and heart failure hospitalization in patients with and without diabetes.
• This review discusses the potential mechanisms by which SGLT2 inhibitors exert their beneficial effects, including beneficial effects on cardiac energy metabolism, reducing inflammation, improving kidney function, and increasing erythropoiesis.
• Future studies are required to clarify how SGLT2 inhibitors exert their impressive cardiovascular effects, which will allow for a more specific targeting of heart failure therapy.
Recent clinical trials have shown that sodium glucose co-transport 2 (SGLT2) inhibitors have dramatic beneficial cardiovascular outcomes. These include a reduced incidence of cardiovascular death and heart failure hospitalization in people with and without diabetes, and those with and without prevalent heart failure. The actual mechanism(s) responsible for these beneficial effects are not completely clear. Several potential theses have been proposed to explain the cardioprotective effects of SGLT2 inhibition, which include diuresis/natriuresis, blood pressure reduction, erythropoiesis, improved cardiac energy metabolism, inflammation reduction, inhibition of the sympathetic nervous system, prevention of adverse cardiac remodeling, prevention of ischemia/reperfusion injury, inhibition of the Na+/H+-exchanger, inhibition of SGLT1, reduction in hyperuricemia, increasing autophagy and lysosomal degradation, decreasing epicardial fat mass, increasing erythropoietin levels, increasing circulating pro-vascular progenitor cells, decreasing oxidative stress, and improving vascular function. The strengths and weaknesses of these proposed mechanisms are reviewed in an effort to try to synthesize and prioritize the mechanisms as they relate to clinical event reduction.
Dr. Lopaschuk has received speaking honoraria from AstraZeneca; has served as a consultant for Boehringer Ingelheim and Servier; and is a shareholder in Metabolic Modulators Research Ltd. Dr. Verma has received research grants and/or speaking honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, EOCI Pharmacomm Ltd., Janssen, Merck, Novartis, Novo Nordisk, Sanofi, Sun Pharmaceuticals, and the Toronto Knowledge Translation Working Group; is a Tier 1 Canada Research Chair in cardiovascular surgery; and is the president of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received January 22, 2020.
- Revision received February 5, 2020.
- Accepted February 5, 2020.
- 2020 The Authors