title: Cardiovascular outcomes of sodium-glucose cotransporter 2 inhibitors: A comprehensive review of clinical and preclinical studies.
abstract: Diabetes is a leading cause of morbidity and mortality worldwide. Management of diabetes is changing at a rapid pace. Three new classes of antidiabetic drugs including GLP-1 (Glucagon-like peptide 1), DPP-IV (Dipeptidyl peptidase IV) and SGLT2 (Sodium glucose cotransporter 2) inhibitors have been approved in the last few years. Treating diabetes with the antidiabetic drug does not always reduce the cardiovascular complications of diabetes. On the contrary, there was a huge controversy regarding the effect of rosiglitazone on cardiovascular risk reduction a few years ago. Since then, submission of postmarketing cardiovascular outcome study data has been mandated by US FDA and other drug regulatory agencies for newer antidiabetic medications. This is to avoid further premature claims regarding cardiovascular harm or safety of the newer classes. We already have some cardiovascular safety data available on DPP-IV and GLP-1 groups of medications. Dapagliflozin, canagliflozin, and empagliflozin are currently approved SGLT2 inhibitors. We do not have sufficient cardiovascular outcome data available for this novel class. However, this group of drugs, which act by increasing renal glucose excretion, have also shown some non-glycemic benefits including weight reduction, blood pressure control, diuretic action, renal protection, decrease in arterial stiffness and uric acid reduction. Empagliflozin, a new member of SGLT2 class, showed significant cardiovascular morbidity and mortality benefit in recently published EMPA-REG OUTCOME trial. The authors summarize all the published clinical and preclinical cardiovascular outcome data of SGLT2 inhibitors, including recently completed and ongoing major clinical trials in this comprehensive review.
authors.affiliation: Department of Cardiovascular Medicine, St. Vincent Charity Medical Center, A Teaching Affiliate of Case Western Reserve University, Cleveland, OH, USA. Electronic address: raktimghoshmd@gmail.com.
authors.forename: Raktim Kumar
authors.initials: RK
authors.lastname: Ghosh
authors.affiliation: Department of Emergency Medicine, Lady Hardinge Medical College, New Delhi, India.
authors.forename: Dhrubajyoti
authors.initials: D
authors.lastname: Bandyopadhyay
authors.affiliation: Department of Internal Medicine, IPGMER, Kolkata, India.
authors.forename: Adrija
authors.initials: A
authors.lastname: Hajra
authors.affiliation: Department of Cardiology, Geisinger CMC Hospital and Wright Center for Graduate Medical Education, Scranton, PA, USA.
authors.forename: Monodeep
authors.initials: M
authors.lastname: Biswas
authors.affiliation: Department of Cardiovascular Medicine, St. Vincent Charity Medical Center, A Teaching Affiliate of Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Anjan
authors.initials: A
authors.lastname: Gupta
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D002986:Clinical Trials as Topic / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D012307:Risk Factors; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism*; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin
keywords: CANVAS; CREDENCE; Canagliflozin; Cardiovascular outcomes; DECLARE-TIMI 58; Dapagliflozin; Empagliflozin; Nonglycemic benefit of SGLT2 inhibitors; SGLT2 Inhibitors