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Context Inhibitors of sodium-glucose cotransporters-2 have cardio- and renoprotective properties. However, the underlying mechanisms remain indeterminate. Objective To evaluate the effect of dapagliflozin on renal metabolism assessed by urine metabolome analysis in patients with type 2 diabetes. Design Prospective cohort study. Setting Outpatient diabetes clinic of a tertiary academic center. Patients Eighty patients with hemoglobin A1c > 7% on metformin monotherapy were prospectively enrolled. Intervention Fifty patients were treated with dapagliflozin for 3 months. To exclude that the changes observed in urine metabolome were merely the result of the improvement in glycemia, 30 patients treated with insulin degludec were used for comparison. Main Outcome Measure Changes in urine metabolic profile before and after the administration of dapagliflozin and insulin degludec were assessed by proton-nuclear magnetic resonance spectroscopy. Results In multivariate analysis urine metabolome was significantly altered by dapagliflozin (R2X = 0.819, R2Y = 0.627, Q2Y = 0.362, and coefficient of variation analysis of variance, P Conclusions Dapagliflozin significantly affects urine metabolome in patients with type 2 diabetes in a glucose lowering-independent way. Most of the observed changes can be considered beneficial and may contribute to the renoprotective properties of dapagliflozin.

Introduction: The efficacy and safety of IDegLira and the benefits of its complementary mode of action have been examined in the large global DUAL clinical trial program. Aim: The aim of this study is to examine the qualitative and quantitative effect of IDegLira compared to the non-fixed adiministration of degludec and liraglutide. Methods: Uncontrolled type 2 diabetes (T2D) patients (n=473) were included in the study. 158 patients on oral antidiabetic drugs (OADs) switched to OADs and IDegLira (Group A), 163 on OADs and liraglutide switched to degludec and the existing therapeutic regime (Group B) and 152 patients on degludec and OADs switched to liraglutide and the existing treatment (Group C). All patients also received metformin while none of them received sulfonylurea. Follow-up was 12 months and changes in HbA1c, cardiometabolic risk factors, and treatment adherence (with the 8-item Morisky Medication Adherence Scale) were recorded. Results: There was no difference at baseline between the three Groups as to age (p=0.224), diabetes duration (p=0.322), HbA1c (8.56±1.12, p=0.116) and BMI (32.14±3.56, p=0.142). The mean HbA1c after 12 months was 6.79±0.77, 7.14±1.19, 7.18±1.07 (p=0.033) for Groups A, B and C respectively. More patients achieved the therapeutic target for HbA1c in Group A (p=0.048). The weight change was -3.2±1.2 Kg for Group A, 1.2±1.1 Kg for Group B and -4.3±1.7 Kg for Group C (p Conclusions: Uncontrolled patients on oral antidiabetic drugs when switched to a therapeutic regimen with IDegLira achieved a significant improvement in their glycemic control with a significant adherence to their therapeutic regimen while the adherence in a non-fixed combination was not significant enough. Disclosure A. Koutsovasilis: None. A. Sotiropoulos: None. D. Papadaki: None. E. Bletsa: None. G. Kokotos: None. I. Kounelakis: None. S. Bousboulas: None. T. Peppas: None.