Context: Reduction in the levels of circulating stem cells (CSCs) and endothelial progenitor cells (EPCs) predicts development or progression of microangiopathy and macroangiopathy in patients with type 2 diabetes (T2D). Objective: We tested whether treatment with sodium glucose cotransporter-2 (SGLT2) inhibitors affected the levels of CSCs and EPCs. Design: A randomized trial of dapagliflozin vs placebo with open-label extension, and an open-label observational study of empagliflozin treatment. Setting: Tertiary referral diabetes outpatient clinic. Patients: Patients with T2D aged 18 to 75 years. Intervention: Dapagliflozin at 10 mg vs placebo (n = 31); empagliflozin at 10 mg (n = 15). Main Outcome Measures: We measured CSCs (CD34+) and EPCs (CD34+KDR+) by flow cytometry at baseline, at 12 weeks, and after the extension period. Results: After 12 weeks, CSCs declined nonsignificantly in the dapagliflozin group, remained stable in the placebo group, and the change from baseline was not significantly different between the two groups. EPCs declined nonsignificantly in the dapagliflozin group, increased nonsignificantly in the placebo group, and the change from baseline was significantly different between the two groups. After an open-label extension period of about 1.5 years, CSCs remained stable over time, whereas EPCs significantly increased in patients who received dapagliflozin. In all patients, irrespectively of treatment, EPCs increased significantly from baseline to the end of observation, concomitantly with improvement in HbA1c. In a cohort of 15 patients who received open-label empagliflozin for 12 weeks, CSCs declined nonsignificantly, whereas EPCs remained stable. Conclusion:SGLT2 inhibitors do not significantly increase CSCs or EPCs. Thus, cardiovascular protection by SGLT2 inhibitors may not directly involve stem/progenitor cells.
RCT Entities:
Context: Reduction in the levels of circulating stem cells (CSCs) and endothelial progenitor cells (EPCs) predicts development or progression of microangiopathy and macroangiopathy in patients with type 2 diabetes (T2D). Objective: We tested whether treatment with sodium glucose cotransporter-2 (SGLT2) inhibitors affected the levels of CSCs and EPCs. Design: A randomized trial of dapagliflozin vs placebo with open-label extension, and an open-label observational study of empagliflozin treatment. Setting: Tertiary referral diabetesoutpatient clinic. Patients: Patients with T2D aged 18 to 75 years. Intervention: Dapagliflozin at 10 mg vs placebo (n = 31); empagliflozin at 10 mg (n = 15). Main Outcome Measures: We measured CSCs (CD34+) and EPCs (CD34+KDR+) by flow cytometry at baseline, at 12 weeks, and after the extension period. Results: After 12 weeks, CSCs declined nonsignificantly in the dapagliflozin group, remained stable in the placebo group, and the change from baseline was not significantly different between the two groups. EPCs declined nonsignificantly in the dapagliflozin group, increased nonsignificantly in the placebo group, and the change from baseline was significantly different between the two groups. After an open-label extension period of about 1.5 years, CSCs remained stable over time, whereas EPCs significantly increased in patients who received dapagliflozin. In all patients, irrespectively of treatment, EPCs increased significantly from baseline to the end of observation, concomitantly with improvement in HbA1c. In a cohort of 15 patients who received open-label empagliflozin for 12 weeks, CSCs declined nonsignificantly, whereas EPCs remained stable. Conclusion:SGLT2 inhibitors do not significantly increase CSCs or EPCs. Thus, cardiovascular protection by SGLT2 inhibitors may not directly involve stem/progenitor cells.
Authors: Seshagiri Rao Nandula; Nabanita Kundu; Hassan B Awal; Beda Brichacek; Mona Fakhri; Nikhila Aimalla; Adrian Elzarki; Richard L Amdur; Sabyasachi Sen Journal: Cardiovasc Diabetol Date: 2021-02-13 Impact factor: 9.951
Authors: Benedetta Maria Bonora; Roberta Cappellari; Marco Grasso; Marta Mazzucato; Marianna D'Anna; Angelo Avogaro; Gian Paolo Fadini Journal: Diabetes Ther Date: 2022-06-09 Impact factor: 3.595