GLP-1 and SGLT2 Combinations Show Enhanced Benefit in ASCVD and Heart Failure Patients

GLP-1s and SGLT2s: A Potent Duo for Heart Health in ASCVD and Heart Failure Patients

October 27, 2023 – For individuals managing both atherosclerotic cardiovascular disease (ASCVD) and heart failure, a powerful therapeutic synergy is emerging. Recent insights highlight the significant advantages of combining glucagon-like peptide-1 receptor agonists (GLP-1s) and sodium-glucose cotransporter-2 inhibitors (SGLT2s).

This dual-action approach appears to be more effective than either medication class alone in improving outcomes. The findings offer renewed optimism for patients facing complex cardiac challenges.

GLP-1s,known for their role in blood sugar regulation and appetite control,have demonstrated cardiovascular benefits. Similarly, SGLT2s have shown remarkable efficacy in reducing heart failure hospitalizations

What are the key mechanisms by which GLP-1 RAs and SGLT2is synergistically reduce cardiovascular risk in ASCVD and heart failure patients?

Understanding the Synergistic Effects of GLP-1 Receptor Agonists and SGLT2 Inhibitors

The landscape of cardiovascular disease management is rapidly evolving, with recent research highlighting the remarkable benefits of combining GLP-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is). This combination therapy is demonstrating particularly strong efficacy in patients with atherosclerotic cardiovascular disease (ASCVD) and heart failure, nonetheless of diabetes status. Both drug classes initially developed for type 2 diabetes, now stand as cornerstones in modern cardiology.

How GLP-1 Receptor Agonists Benefit cardiovascular health

GLP-1 RAs mimic the effects of the naturally occurring incretin hormone, GLP-1. Their mechanisms extend beyond glucose control, offering significant cardiovascular protection:

Improved Glycemic Control: GLP-1 RAs enhance insulin secretion and suppress glucagon, leading to better blood sugar management. This is crucial for reducing cardiovascular risk factors.

Weight Loss: A common side effect, and often a beneficial one, is weight reduction. Obesity is a major contributor to both ASCVD and heart failure.

Blood Pressure Reduction: GLP-1 RAs can modestly lower blood pressure, further reducing cardiovascular strain.

Plaque Stabilization: Emerging evidence suggests GLP-1 RAs may stabilize existing atherosclerotic plaques, reducing the risk of rupture and subsequent cardiovascular events.

Reduced Inflammation: GLP-1 RAs exhibit anti-inflammatory properties, addressing a key driver of atherosclerosis.

Common GLP-1 RA medications include semaglutide (Ozempic, Rybelsus, Wegovy), liraglutide (Victoza), and dulaglutide (Trulicity).

The Role of SGLT2 Inhibitors in Cardiovascular Protection

SGLT2 inhibitors work by blocking the reabsorption of glucose in the kidneys, leading to increased glucose excretion in the urine. However, their cardiovascular benefits are autonomous of their glucose-lowering effects:

Diuretic Effect: SGLT2is promote sodium and water excretion, reducing blood volume and cardiac workload.

Improved Cardiac Efficiency: These drugs shift cardiac energy substrate utilization towards more efficient pathways.

Reduced Arterial Stiffness: SGLT2is have been shown to improve arterial compliance, reducing the burden on the heart.

Decreased Hospitalizations for Heart Failure: Landmark trials have demonstrated significant reductions in heart failure hospitalizations and cardiovascular death with SGLT2i use.

Kidney Protection: SGLT2 inhibitors offer renoprotective benefits, slowing the progression of chronic kidney disease, a common comorbidity in ASCVD and heart failure.

Popular SGLT2 inhibitors include empagliflozin (Jardiance), dapagliflozin (Farxiga), and canagliflozin (Invokana).

Why Combine GLP-1 RAs and SGLT2is? The Synergy Explained

The combination of GLP-1 RAs and SGLT2is offers a synergistic approach to cardiovascular risk reduction. Their mechanisms complement each other, addressing multiple facets of ASCVD and heart failure pathophysiology.

Complete risk Factor Management: The combination tackles hyperglycemia, obesity, hypertension, and inflammation together.

Enhanced Cardiac Protection: Both drug classes independently protect the heart; together,their effects are amplified.

Improved Outcomes in High-Risk Patients: Clinical trials demonstrate superior outcomes in patients with established ASCVD or heart failure when treated with both a GLP-1 RA and an SGLT2i.

Potential for Disease Modification: Beyond symptom management, this combination may slow the progression of underlying cardiovascular disease.

Evidence from Landmark Clinical Trials

Several pivotal trials have shaped our understanding of this combination therapy:

SELECT Trial (semaglutide and Cardiovascular Outcomes in Adults with Established cardiovascular Disease): Showed a significant reduction in major adverse cardiovascular events (MACE) with semaglutide in patients without type 2 diabetes but with established cardiovascular disease.

**EMPEROR-Reduced & EMPEROR-Preserved (Empagliflozin