Cardioprotective Effects of Antidiabetic Medications in Type 2 Diabetes - Mechanisms and Clinical Outcomes: A Narrative Review
Abstract
Purpose: This comprehensive review examines the cardiovascular (CV) impact of four key antihyperglycemic drug classes—metformin, DPP-4 inhibitors (DPP-4is), GLP-1 receptor agonists (GLP-1 RAs), and SGLT2 inhibitors (SGLT2is)—analyzing their mechanisms of action, clinical trial findings, and therapeutic applications for managing type 2 diabetes mellitus (T2DM) and reducing CV complications. Results: Metformin demonstrates CV risk reduction through pleiotropic mechanisms, though its relative effectiveness compared to newer agents requires further investigation. DPP-4i maintain CV safety in trials like TECOS and CAROLINA, though saxagliptin shows increased HF hospitalization risk in vulnerable populations, particularly those with pre-existing HF or CKD. GLP-1 Ras, especially long-acting formulations (liraglutide, semaglutide), significantly decrease major adverse cardiovascular events (MACE) and mortality rates, with dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) agonists (tirzepatide) emerging as promising therapies for heart failure with preserved ejection fraction (HFpEF). SGLT2is demonstrate consistent benefits, reducing HF hospitalizations by 24-30% and CV mortality by 38% (empagliflozin), with effects extending beyond diabetic populations. Conclusions: Contemporary T2DM management emphasizes organ-protective strategies. While GLP-1 RAs and SGLT2is provide substantial CV advantages, DPP-4is necessitate careful patient selection.…
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