Effects of Dapagliflozin Treatment on Urinary Proteomic Patterns in Patients With Type 2 Diabetes

Background: SGLT2 inhibitors are the first antiglycaemic drugs with a direct renal action. A part from reducing blood glucose, systemic blood pressure and albuminuria are decreased, while natriuresis is increased. Previous research into urinary peptide patterns (proteomics) has revealed that patients in risk of progressive renal disease display a "risk peptide pattern" in their urine, ahead of decline in renal function. Furthermore a urinary proteome pattern is related to CVD risk. The long-term impact of dapagliflozin (dapa) treatment on renal parameters is unknown, but long term randomized trials are ongoing. By investigating the impact of dapa treatment on this peptide pattern, it will be determined whether this intervention can improve the urinary proteomic peptide pattern. In addition new knowledge regarding renal processes that the treatment influences is sought. The impact of treatment of urinary and tubular markers of oxidative stress and function (metabolomics) will be assessed. These markers are thought to represent one of several deleterious pathways involved in the pathology of diabetic renal disease, and here the impact dapa treatment will be investigated. Improvement of these markers of oxidative stress may indicate long-term benefit. Objective: The primary objective is to assess the impact of three months of treatment with dapa 10 mg once daily or placebo on renal proteomics pattern and other risk markers of diabetic comorbidity. Design: Double blinded, randomized, placebo-controlled crossover, single center study. Treatment period: 2 x 12 weeks. Patient population: 40 patients with type 2 diabetes recruited from Steno Diabetes Center in accordance with the study in- and exclusion criteria. Intervention: Dapa 10 mg daily vs. placebo. Endpoints: Primary outcome: To evaluate the effect of dapa treatment on urinary proteomic patterns in patients with type 2 diabetes, microalbuminuria and eGFR equal to or above 45 ml/min/1.73m2. Secondary endpoint