PMID- 29679303 OWN - NLM STAT- MEDLINE DCOM- 20190114 LR - 20190114 IS - 1573-7241 (Electronic) IS - 0920-3206 (Linking) VI - 32 IP - 2 DP - 2018 Apr TI - Do the SGLT-2 Inhibitors Offer More than Hypoglycemic Activity? PG - 213-222 LID - 10.1007/s10557-018-6786-x [doi] AB - Type 2 diabetes mellitus (T2DM) is one of the most common chronic health conditions in the USA; it affects approximately 10% of adults with up to one-quarter being undiagnosed. T2DM is associated with substantial cardiovascular (CV) morbidity and mortality. T2DM is a pathological condition characterized by elevated levels of glucose and associated with high CV risk. Traditional hypoglycemic drugs have demonstrated their capability for effective and maintained management of high glucose levels, but they have not significantly impacted on the incidence of CV events. Recently, a new class of hypoglycemic agents, SGLT-2 receptor inhibitors, has been developed. The EMPA-OUTCOME trial involving empagliflozin (a SGLT-2 receptor inhibitor) has shown significant reductions in major adverse cardiac events (MACEs), cardiovascular mortality, and hospitalization for heart failure (HF) when administered on top of standard-of-care therapy for T2DM patients at high CV risk. The dramatic change driving the superiority of the primary composite outcome (major adverse CV events) was a significantly lower CV death rate (38% relative risk reduction). In addition, there were also an impressive 35 and 32% relative risk reductions in hospitalization for heart failure (HF) and death from any cause, respectively. These effects are even more important given the difficulties for treating concomitant HF in T2DM patients. These surprising results have been also corroborated by another agent of this class, canagliflozin, and the CANVAS trial. The magnitude of these somehow surprising cardiac benefits attained in the absence of major differences in glycemic, lipid, or blood pressure (BP) control has led to several groups to suggest that these benefits may be independent of its hypoglycemic activity and whether this new class could be considered a "cardiac" drug. The objective of this review has been to review the different hypotheses proposed to explain the cardiac benefits of this new class of antidiabetic drugs. FAU - Flores, Eduardo AU - Flores E AD - Cardiology Department, Clinic Hospital, Barcelona, Spain. AD - Atherothrombosis Research Unit, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, USA. FAU - Santos-Gallego, Carlos G AU - Santos-Gallego CG AD - Atherothrombosis Research Unit, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, USA. FAU - Diaz-Mejia, Nely AU - Diaz-Mejia N AD - Hospital Vall d'Hebron, Barcelona, Spain. FAU - Badimon, Juan Jose AU - Badimon JJ AUID- ORCID: 0000-0002-6780-8771 AD - Atherothrombosis Research Unit, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, USA. Juan.Badimon@mssm.edu. LA - eng PT - Journal Article PT - Review PL - United States TA - Cardiovasc Drugs Ther JT - Cardiovascular drugs and therapy JID - 8712220 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Animals MH - Biomarkers/blood MH - Blood Glucose/*drug effects/metabolism MH - Cardiovascular Diseases/blood/diagnosis/*drug therapy/epidemiology MH - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy/epidemiology MH - Humans MH - Risk Factors MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/*therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - Cardiac magnetic resonance OT - Cardiovascular diseases OT - Empagliflozin OT - Heart failure OT - SGLT-2 receptor inhibitors OT - Type 2 diabetes mellitus EDAT- 2018/04/22 06:00 MHDA- 2019/01/15 06:00 CRDT- 2018/04/22 06:00 PHST- 2018/04/22 06:00 [pubmed] PHST- 2019/01/15 06:00 [medline] PHST- 2018/04/22 06:00 [entrez] AID - 10.1007/s10557-018-6786-x [pii] AID - 10.1007/s10557-018-6786-x [doi] PST - ppublish SO - Cardiovasc Drugs Ther. 2018 Apr;32(2):213-222. doi: 10.1007/s10557-018-6786-x.