Effectiveness and Safety of Combined Semaglutide and Dapagliflozin Therapy in Type 2 Diabetes: A Retrospective Cohort Study.

backgroundCombination therapy with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors may provide complementary metabolic, cardiovascular, and renal benefits in type 2 diabetes mellitus (T2DM). However, real-world evidence from Middle Eastern populations remains limited. This study evaluated the effectiveness and safety of combined semaglutide and dapagliflozin therapy in routine clinical practice.

methodsThis retrospective cohort study included adults (≥18 years) with T2DM treated with concurrent semaglutide and dapagliflozin for at least 12 months at a specialized primary care clinic in King Abdulaziz Medical City, Jeddah, Saudi Arabia. Clinical and laboratory data were extracted from electronic medical records. The primary outcome was a change in glycated hemoglobin (HbA1c). Secondary outcomes included changes in the lipid profile, renal parameters (estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR)), and adverse events. Paired comparisons were performed using the Wilcoxon signed-rank test. Multivariable linear regression was used to identify predictors of HbA1c reduction.

resultsA total of 291 patients were included (mean age 58.6 ± 9.5 years; 49.8% male; mean diabetes duration 12.9 ± 9.5 years). Median HbA1c decreased from 8.20% to 7.20% (Z = -10.323; P < 0.001). Significant reductions were also observed in total cholesterol, LDL cholesterol, and triglycerides (all P < 0.001), while the UACR decreased significantly (P < 0.001). eGFR remained stable (P = 0.376). Most patients (90.4%) experienced no documented adverse events; hypoglycemia occurred in 6.2%. In multivariable analysis, higher baseline HbA1c (B = 0.552; P < 0.001), hypertension (B = 0.413; P = 0.016), and dyslipidemia (B = 0.381; P = 0.021) were associated with greater HbA1c reduction, whereas insulin use was associated with a smaller reduction (B = -0.612; P < 0.001). The model explained 43.2% of the variability in HbA1c change.

conclusionsIn routine clinical practice, combined semaglutide and dapagliflozin therapy was associated with significant improvements in glycemic control, lipid profile, and albuminuria, with stable renal function and a favorable safety profile. These findings support the effectiveness of this combination in real-world settings and highlight the need for prospective comparative studies to confirm long-term outcomes and define optimal patient selection.