Abstract 13622: Effect of Dapagliflozin and Saxagliptin Combination on CD34+ve Endothelial Progenitor Cells (EPCs) in Type 2 Diabetes Subjects

Abstract

Introduction: We examined the effect of Dapagliflozin (Dapa) and Dapagliflozin-Saxagliptin combination (Combo) on EPCs in Type-2-Diabetes (T2DM) subjects as a cellular cardiovascular biomarker. Both Dapa (a SGLT2 receptor inhibitor) and Saxagliptin (a DPP4 enzyme inhibitor) are T2DM medications, but the combination has not been evaluated for cardiovascular outcomes, using stem cells. Hypothesis: We hypothesized that Dapa will improve EPC number and function compared to placebo and Combo may have additional positive effects. Methods: In this pilot study, 15 subjects were enrolled in 16 weeks, double-blind, randomized placebo matched trial, with 3 arms: 10mg Dapa + Saxa placebo (n=4), 10 mg Dapa + 5 mg Saxa (n=5) Combo, And Dapa placebo + Saxa placebo (n=6), Placebo groups. T2DM (30-70 years) and HbA1c of 7-10%, were included. HbA1C between 7 to 8 was maintained. Peripheral blood derived CD34+ EPC number, migratory function, mRNA gene expression along with arterial stiffness, biochemistry, resting energy expenditure, and body composition were measured. Data were collected at weeks 0, 8, and 16. A mixed model regression analysis was done with a p-value <0.05 considered significant. Results: A significant decreased glucose (p=0.0317) and HbA1c (p=0.0357) levels were noted in Combo group compared to Dapa and more so compared to Placebo. hsCRP levels (P=0.0317)) are significantly reduced in both Dapa and Combo (to a similar extent) vs Placebo. The LDL/HDL ratio is significantly reduced (p=0.05) in combination group as compared to either Dapa alone or Placebo group. Leptin levels decreased significantly in both Dapa alone (p=0.035) and Combo group(p=0.015) , to a similar extent vs Placebo. EPC migration improved significantly in both Dapa alone (p=0.05) and Combo group (p=0.05) , to a similar extent, vs Placebo. Both Serum IL-6 levels and IL6-mRNA expression on EPCs showed significant reduction in both Dapa and Combo (to a similar extent) vs Placebo. Conclusions: Our study indicates that several parameters showed significant differences of Dapa and Combo when compared to placebo. However, other than glycemic control the Combo did not offer any further benefit over Dapa alone as far as inflammatory markers or stem cell number or migration properties were concerned.