In this observational study, 60 subjects with type 2 diabetes (T2D) and eligible, as per good clinical practice, for therapy with SGLT-2 inhibitor, will be randomized to receive a SGLT-2 inhibitor or a fixed dose combination of SGLT-2 inhibitor with a DPP4-inihibitor for 12 weeks. Measures will be performed at baseline and after 12 weeks of treatment, as per good clinical practice.

The day of the study patients undergo a routine clinical evaluation. Whole blood samples will be collected from an antecubital vein to assess serum/plasma aliquots of 200 μl each (frozen at -80°C until required for quantitation) for evaluation of biochemical parameters (fasting glucose, HbA1c, lipid profile, serum creatinine, uric acid, electrolytes, liver function enzymes, albumin).

A mid-stream first urine in the morning sample will be collected into a sterile container. 50 ml of urine will be immediately transferred into a sterile falcon and centrifugated at 4500 rpm for 10 min. After removal of the supernatant and addition of 10 ml of PBS or sterile physiological solution, the sample will be further centrifugated at 4500 rpm for 10 min. The supernatant will be removed and the pellet stored in a falcon at -80°C.

Genomic DNA will be extracted throw Qiamp DNA mini kit (QIAGEN) and quantified using spectrophotometric assay.

Inclusion Criteria:

• Type 2 diabetes diagnosis
• Hb1Ac ≥ 7% and ≤ 9%

Exclusion Criteria:

• Hb1Ac > 9%
• current treatment with an SGLT2i or a DPP4i drugs, or in the prior 4 week
• irritating and/or obstructive urinary or genital symptoms
• menstrual cycle for women
• current antibiotic treatment or in the prior 4 weeks
• anatomical or functional abnormalities of the urinary tract (e.g. incontinence, neurological bladder, bladder prolapse).

The study will consecutively enrolled 60 patients among those referring to the Departiment of Diabetes and Metabolic disease, Santa Chiara Hospital, Pisa.