Rasmah Alharajin, Muneera AlTaweel, Maram AlSubaiee, Saleh Al Makhloof, Abdulmohsen Almusaad, Abdulrahman Alarfaj, Ahmad AlKhayyal, Noor Altharman, Ahmed Alalawi, Noora Almannai, Munirah Alohaymid, Afnan Alsaad, Turkiah Alotaibi, Reem Alkhaldi, Ghusoon Almoaibed, Jawaher Alrashada, Abdullatif Alarfaj, Turki Alqarni, Abdullah Alshahrani, Ibraheem Aldossary, Seham Khashwayn, Ali Al Qarni, Yaqob Taleb, Mareyah Alshaikh Husain
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.
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.