CARDIOMETABOLIC AND RENOPROTECTIVE EFFECTS OF GLP-1 RECEPTOR AGONISTS AND SGLT2 INHIBITORS IN TYPE 2 DIABETES MELLITUS: A SYSTEMATIC REVIEW

Abstract

Background: GLP-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors (SGLT2i) reduce cardiometabolic and renal complications in type 2 diabetes mellitus (T2DM), yet their relative benefits remain incompletely characterised.

Methods: PRISMA 2020-compliant systematic review of randomised controlled trials identified through PubMed, Scopus, Web of Science, and CENTRAL (January 2008–December 2024). Risk of bias was assessed using RoB 2 and evidence certainty using GRADE.

Results: Thirty-five studies were included (11 landmark RCTs; N > 93,000). Both classes reduced MACE comparably versus placebo. SGLT2i demonstrated superior heart failure hospitalisation reduction and consistent attenuation of eGFR decline, UACR, and ESKD across CREDENCE, DAPA-CKD, and EMPA-KIDNEY. The FLOW trial established the first hard renal endpoint reduction with a GLP-1 RA (semaglutide; HR 0.76, 95% CI 0.66–0.88). GLP-1 RAs achieved greater HbA1c and body weight reductions. Combination therapy reduced MACE and serious renal events by approximately 30% versus monotherapy. GRADE certainty was high for MACE and heart failure outcomes.

Conclusion: GLP-1 RAs and SGLT2i offer complementary, non-redundant cardiorenal protection in T2DM. SGLT2i are preferred when heart failure or CKD predominates; GLP-1 RAs offer superior atherosclerotic and metabolic benefits. Individualised selection guided by dominant comorbidity, in alignment with ESC, ADA, and KDIGO guidelines, is recommended.