Abstract 691: Cardio-renal Effect Of Dapagliflozin Alone Versus Dapagliflozin- Saxagliptin Combination In Type 2 Diabetes (t2dm) Subjects

Abstract

Introduction: Effect of Dapagliflozin (Dapa) and Dapagliflozin-Saxagliptin combination (Combo) was examined on peripheral blood derived CD34+ HSCs as a cellular CVD biomarker. Both Dapa (a SGLT2 receptor inhibitor) and Saxagliptin (a DPP4 enzyme inhibitor) are T2DM meds, but the combo has not been evaluated for cardio-renal risk. Hypothesis: We hypothesized that Dapa will improve the outcomes when compared to placebo and the Combo maybe even more beneficial. Methods: 15 subjects were enrolled in 16 weeks, double-blind, three-arm, randomized placebo matched trial, with 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 yrs) with HbA1c of 7-10%, were included. CD34+ HSC number, migration, mRNA expression along with biochemistry and urine exosomes were measured. Data were collected at wks 0, 8, and 16. For stats, a mixed model regression analysis was used. Results: Significant HbA1c (p=0.0357) reduction was noted in Combo group vs Dapa alone and Placebo. hsCRP levels (P=0.0317) and IL-6, two important inflammatory molecules, were significantly reduced in both Dapa and Combo vs Placebo. Leptin levels decreased significantly in both Dapa alone (p=0.035) and Combo group(p=0.015), vs Placebo, however the Adiponectin levels were higher in Dapa alone group. EPC migration improved significantly in both Dapa alone (p=0.05) and Combo group (p=0.05) vs Placebo. Interestingly, urine exosome-based podocyte specific protein such as podocalyxin was actually higher in Combo vs Control. Conclusions: Several parameters showed significant improvement with both Dapa and Combo vs placebo. However, other than glycemic control the Combo didn’t offer any further benefit over Dapa alone in terms of HSC, biochemistry and podocyte markers. Of note, the combination may have deleterious effect on renal podocyte inflammation which needs to be examined in a larger study.