Novel Anti-glycemic Drugs and Reduction of Cardiovascular Risk in Diabetes: Expectations Realized, Promises Unmet.
OBJECTIVE
The purpose is to review evidence on cardiovascular risks and benefits of new treatments for type 2 diabetes mellitus.


RESULTS
In response to guidance issued by the Food and Drug Administration, thousands of patients have been enrolled in large randomized trials evaluating the cardiovascular effects of the three newest diabetes drug classes: glucagon-like peptide-1 (GLP-1) receptor agonists, sodium glucose cotransporter 2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors. Two studies of GLP-1 receptor agonists-one of liraglutide and one of semaglutide-have shown cardiovascular benefit relative to placebo, and one study of the SGLT-2 inhibitor empagliflozin has shown benefit. The other published cardiovascular outcome studies of the newest drug classes have generally supported safety, apart from an as-yet unresolved safety concern about increased rates of heart failure with DPP-4 inhibitors. Recent research suggests the thiazolidinedione pioglitazone may have beneficial effects on some cardiovascular outcomes as well, but these are counterbalanced by a known increase of the risk of heart failure with this drug. In general, more prospective randomized trial data is now available regarding the cardiovascular effects of the newer diabetes drugs than on the older drug classes. New evidence suggests that the newest diabetes drugs are safe from a cardiovascular perspective. Evidence on benefit from at least some members of the GLP-1 receptor agonist and SGLT-2 inhibitor classes is encouraging but not yet decisive.
Weill Cornell Medical College, 425 E 61st Street, Suite 301, New York, NY, 10065, USA. jaf9052@med.cornell.edu.
James H
JH
Flory
Weill Cornell Medical College, 425 E 61st Street, Suite 301, New York, NY, 10065, USA.
Jenny K
JK
Ukena
Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
James S
JS
Floyd
D000818:Animals; D001786:Blood Glucose; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors
D001786:Blood Glucose; D007004:Hypoglycemic Agents
Cardiovascular outcomes; Cardiovascular risk; Cardiovascular safety; Novel anti-glycemic drugs; Type 2 diabetes mellitus