Dapagliflozin Alone or Combined With Semaglutide: Cardiovascular and Renal Outcomes Among Patients With Type 2 Diabetes Mellitus in a 6-Month Real-World Retrospective Cohort Study in Saudi Arabia.

INTRODUCTION

Type 2 diabetes mellitus (T2DM) is a growing global health concern linked to increased cardiovascular and renal complications. Two emerging therapeutic classes, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon like peptide-1 receptor agonists (GLP-1 RAs), have shown independent cardiometabolic benefits. However, limited realworld data exist on the comparative impact of combining these therapies versus using SGLT2i alone.

OBJECTIVE

To compare the cardiovascular and renal outcomes of dapagliflozin monotherapy versus combination therapy with once-weekly injectable semaglutide among patients with type 2 diabetes mellitus (T2DM).

METHODOLOGY: In this retrospective cohort study, 539 adult patients with confirmed type 2 diabetes mellitus (T2DM; baseline HbA1c ≥6.5%) treated at King Abdulaziz Hospital, Al-Ahsa, were followed over six months. Patients received either dapagliflozin alone or in combination with semaglutide. Generalized Estimating Equations (GEE) were used to assess changes in glycemic control, cardiovascular events, lipid profile, and renal function, adjusting for time and sex.

RESULTS

Both groups showed significant metabolic improvements over six months. Dapagliflozin monotherapy was associated with greater HbA1c reduction. Combination therapy was associated with higher HDL levels, improved eGFR, and a lower relative risk of heart failure (RR = 0.43, p = 0.04); the reduction in myocardial infarction risk (RR = 0.61, p = 0.13) did not reach statistical significance. No significant difference was observed in stroke risk. Most cardiovascular and renal markers improved modestly.

CONCLUSION

Combination therapy was associated with favorable renal outcomes and a reduction in heart failure risk, despite inferior glycemic control and a non-significant trend toward reduced myocardial infarction risk. These findings suggest potential complementary effects of SGLT2i and GLP-1 RA treatment in high-risk patients. However, due to the retrospective, non-randomized design, causal relationships cannot be inferred, and residual confounding may exist. Prospective trials are warranted to confirm these associations and guide treatment optimization.