The Changing Landscape of Diabetes Therapy for Cardiovascular Risk Reduction: JACC State-of-the-Art Review

Area of Science:

• Cardiology
• Endocrinology
• Pharmacology

Background:

• Type 2 diabetes (T2D) significantly increases cardiovascular disease (CVD) risk, the leading cause of mortality in T2D patients.
• Despite advancements in risk factor management, a substantial residual CVD risk persists in adults with T2D.
• Historically, improved glycemic control alone has not demonstrated significant macrovascular benefits.

Purpose of the Study:

• To review recent cardiovascular outcome trial evidence for novel antihyperglycemic agents.
• To discuss the mechanisms of action, safety profiles, and clinical applications of SGLT2 inhibitors and GLP-1 receptor agonists.
• To evaluate the role of these agents in primary CVD prevention and in patients with diabetic kidney disease and heart failure.

Main Methods:

• Review of large-scale cardiovascular outcome trials (CVOTs) for SGLT2 inhibitors and GLP-1 receptor agonists.
• Analysis of preclinical and clinical data investigating the mechanisms of action.
• Synthesis of safety data and guidelines for clinical use.

Main Results:

• Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated robust cardiovascular benefits.
• These agents offer potential benefits beyond glycemic control, including cardiorenal protection.
• Evidence supports their use in primary CVD prevention and in specific high-risk populations.

Conclusions:

• The advent of SGLT2 inhibitors and GLP-1 receptor agonists represents a paradigm shift in T2D management, prioritizing CVD risk reduction.
• These drug classes are crucial for comprehensive cardiovascular risk management in T2D.
• Their application extends to primary prevention and management of comorbid renal and cardiac conditions in diabetic patients.