Author + information
- Received June 11, 2018
- Revision received June 26, 2018
- Accepted June 27, 2018
- Published online October 1, 2018.
- Thomas A. Zelniker, MD, MSca,b@ZelnikerThomas and
- Eugene Braunwald, MDa,b,∗@TIMIStudyGroup (, )@BrighamWomens
- aTIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts
- bDepartment of Medicine, Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Eugene Braunwald, TIMI Study Group, 60 Fenwood Road, Seventh Floor, Boston, Massachusetts 02115.
Patients with type 2 diabetes mellitus have an increased risk for the development of cardiac and other vascular events, heart failure (HF), and decline in renal function. After several large cardiovascular outcome trials with mostly neutral results, 2 studies of the sodium–glucose co-transporter 2 inhibitors (SGLT2is), empagliflozin and canagliflozin, reported favorable effects on the primary endpoint, a composite of myocardial infarction, stroke, and cardiovascular death. In addition, reductions of hospitalizations for HF were observed; in the case of empagliflozin, reductions in both cardiovascular mortality and total mortality occurred. These findings prompted several analyses to elucidate the mechanisms of action of SGLT2is and have initiated several large clinical trials in patients with HF without type 2 diabetes mellitus. This review summarizes known and possible mechanisms that contribute to these salutary effects of SGLT2is. Also discussed is the interplay between cardiac and renal function, as well as safety issues associated with this class of drugs.
Dr. Zelniker has been funded by the Deutsche Forschungsgemeinschaft (ZE 1109/1-1). Dr. Braunwald has received grant support to his institution from Daiichi-Sankyo, AstraZeneca, GlaxoSmithKline, Merck, and Novartis; has provided uncompensated consultancies and lectures for Merck and Novartis; has received consulting fees from Theravance; and has received personal fees for lectures from Medscape.
- Received June 11, 2018.
- Revision received June 26, 2018.
- Accepted June 27, 2018.
- 2018 American College of Cardiology Foundation