Cardioprotective Effects of Antidiabetic Medications in Type 2 Diabetes - Mechanisms and Clinical Outcomes: A Narrative Review | ||
| Archives of Pharmaceutical Sciences Ain Shams University | ||
| Articles in Press, Accepted Manuscript, Available Online from 15 November 2025 | ||
| Document Type: Review Article | ||
| DOI: 10.21608/aps.2025.393133.1231 | ||
| Authors | ||
| Abdullah Heshmat1; Lamia El Wakeel2; Hazem Khorshid3; sarah f fahmy* 4 | ||
| 1Teaching Assistant clinical pharmacy Ainshams University | ||
| 2Clinical Pharmacy faculty of pharmacy Ain Shams University | ||
| 3Cardiology Department, Ain Shams University, Cairo, Egypt. | ||
| 4clinical pharmacy ainshams university | ||
| Abstract | ||
| 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. Metformin retains its fundamental role, though direct comparisons with newer agents are needed. Tailored treatment plans, incorporating pharmacological mechanisms and individual risk assessment, are crucial for optimizing CV outcomes in T2DM patients. Keywords; Metformin; DPP-4i; GLP-1RAs; SGLT2i; Type 2 diabetes; cardiovascular outcome trials | ||
| Keywords | ||
| Metformin; DPP-4i; GLP-1RAs; SGLT2i; Type 2 diabetes; cardiovascular outcome trials | ||
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