DOI: https://doi.org/10.36347/sajp.2026.v15i06.001

Pages: 133-137

Background: GLP 1 receptor agonists and sodium–glucose co transporter 2 inhibitors independently lower cardiovascular and renal risk in type 2 diabetes. Uptake of concomitant therapy remains limited. Methods: MEDLINE and Embase (1 Jan 2023–30 Jun 2025) identified studies comparing GLP 1 receptor agonists and sodium–glucose co transporter 2 inhibitors vs monotherapy in adults with established atherosclerotic cardiovascular disease and type 2 diabetes (many with CKD). Designs included randomised trials, prespecified trial sub analyses, large registries (≥200 dual therapy users), and systematic reviews. Evidence was stratified as: (A) add sodium–glucose co transporter 2 inhibitors S to GLP 1 receptor agonists; (B) add GLP 1 receptor agonists ao sodium–glucose co transporter 2 inhibitors; (C) head to head registries. Random effects models were applied within strata; heterogeneity was assessed with I2. Results: Six studies met criteria. Head to head registries (n ≈ 41 800) showed pooled HR for 3 point major adverse cardiovascular events of 0.60 (0.50–0.72) vs monotherapy. Adding an sodium–glucose co transporter 2 inhibitors to background dual GLP 1 receptor agonists yielded pooled RR 0.64 (0.46–0.90); adding a GLP 1 RA to background SGLT2I produced HR 0.89 (0.71–1.11). A 2025 RCT rich meta analysis reported similar magnitudes. No excess serious adverse event signal was seen. Conclusion: Across complementary designs – predominantly in adults with established atherosclerotic cardiovascular disease and type 2 diabetes (many with CKD) – dual GLP 1 receptor agonists and sodium–glucose co transporter 2 inhibitors confers ~30–40 % additional 3 point major adverse cardiovascular events reduction vs single agent therapy, with consistent renal benefits and acceptable tolerability. Pending factorial RCTs, early dual initiation is reasonable in highest risk phenotypes, with staggered titration and renal blood pressure monitoring.