Optimal Use of SGLT2 Inhibitors and GLP-1 Agonists: 5 Things to Know

Matthew J. Budoff, MD


October 18, 2021

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For the first time in any trial of hypoglycemic therapy, the EMPA-REG OUTCOME study demonstrated a significant reduction in major adverse cardiovascular events (MACE). This started a plethora of cardiovascular (CV) outcome studies that were positive for reduction in CV death, hospitalizations related to heart failure (HF), improvements in renal function, and prevention of adverse renal outcomes, which added to the positive benefits of these new agents. Coupled with weight reduction — a welcome "side effect" of both the sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists — these medications should become a cornerstone of therapy for our high-risk patients in cardiology.

Here are five things to know about the beneficial role that SGLT2 inhibitors and GLP-1 agonists play in patients with CV disease.

1. Trial data show that SGLT2 inhibitors and GLP-1 agonists reduce MACE in patients with type 2 diabetes.

The first two outcome studies on SGLT2 inhibitors, EMPA-REG OUTCOME and CANVAS, both reported similar positive effects on MACE outcomes in patients with type 2 diabetes and atherosclerotic CV disease, including a reduction in CV death, nonfatal stroke, and nonfatal myocardial infarction of 14%. These findings are especially significant because these therapies were added to background therapy (eg, angiotensin-converting enzyme [ACE] inhibitors or angiotensin II receptor blockers [ARBs], statins, aspirin) in a vast majority of the study participants.

Following EMPA-REG and CANVAS, studies on GLP-1 agonists demonstrated similar benefits on CV outcomes. A series of studies on patients with diabetes and secondary prevention were published, including the LEADER, SUSTAIN-6, and REWIND trials. Data from these trials demonstrated a 12% reduction in MACE in patients receiving liraglutide (LEADER), a 22% reduction in MACE in patients receiving semaglutide (SUSTAIN-6), and a 12% reduction in both primary and secondary MACE in patients receiving dulaglutide (REWIND).


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