Clinical Question

Are dipeptidyl-peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors safe and effective at reducing cardiovascular mortality, all-cause mortality, and other cardiovascular outcomes (e.g., myocardial infarction, stroke, hospitalization from heart failure) in people with cardiovascular disease (CVD)?

Evidence-Based Answer

DPP-4 inhibitors do not reduce mortality or cardiovascular outcomes in people with CVD, and they increase the risk of pancreatitis. (Strength of Recommendation [SOR]: A, consistent, good-quality patient-oriented evidence.)

GLP-1 receptor agonists reduce cardiovascular mortality, all-cause mortality, and stroke in people with CVD. (SOR: A, consistent, good-quality patient-oriented evidence.)

SGLT-2 inhibitors reduce cardiovascular mortality, all-cause mortality, and hospitalization from heart failure in people with CVD.¹ (SOR: A, consistent, good-quality patient-oriented evidence.)

Practice Pointers

In the United States, CVD is the top cause of death, responsible for 24% of all deaths in 2019.² Diabetes mellitus is a leading cause of CVD.³ Although metformin remains the first-line therapy for diabetes, with demonstrated cardiovascular benefit in people with or without diabetes, three newer medication classes were approved recently for diabetes management.⁴ The authors of this review sought to determine if DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors improve outcomes in people with CVD regardless of whether they have diabetes.