SGLT-2 and DPP-4 Inhibition, Subclinical Inflammation of the Genito-urinary Tract and Risk of Infections.

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Use of Combination Empagliflozin/Linagliptin or Dapagliflozin/Saxagliptin vs Empagliflozin or Dapagliflozin Alone, Subclinical Inflammation of the Genito-urinary Tract and Risk of Infections.

Conditions
-----------------
Type 2 Diabetes, Urinary Tract Infections

Intervention / Treatment
-----------------
* Drug: Empagliflozin / Linagliptin or Dapagliflozin/Saxagliptin Pill
* Drug: Empagliflozin or Dapagliflozin Pill


Participation Criteria
=================
Eligibility Criteria
-----------------
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).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SGLT2 and DPP-4 inhibitors<br>Patients undergoing SGLT2i and DPP4i. | Drug: Empagliflozin / Linagliptin or Dapagliflozin/Saxagliptin Pill<br>* association between SGLT2-inhibitor and DPP4-inhibitor<br>* Other names: Glyxambi or Qtern;|
| SGLT2 inhibitors only<br>Patients undergoing SGLT2i alone. | Drug: Empagliflozin or Dapagliflozin Pill<br>* SGLT2-inhibitor: diabetic oral drug with diuretic properties.<br>* Other names: Jardiance or Forxiga;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in metagenomic analysis based on rRNA 16S gene | Metagenomic analysis based on rRNA 16S gene will be performed by Novogene on Illumina platform (Hong Kong, China) | Each patients will be analyzed at baseline and after 12 weeks | 
| Change from Baseline of total bacterial load | Absolute quantification of total bacterial load in the original sample using real-Time quantitative PCR | Each patients will be analyzed at baseline and after 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting glucose | Fasting glucose measured in a fasting morning blood sample | baseline and 12 week | 
| Glycated Haemoglobin | HbA1c in a fasting measured in a morning blood sample | baseline and 12 week | 
| Renal function | Using creatinine measured in a fasting morning blood sample and estimated by eGFR (calculated with the CDK-EPI formula) | baseline and 12 week | 
| Albumin excretion | Measured by urinary albumin/creatinine ratio | baseline and 12 week | 
| Total cholesterol | Total cholesterol measured in a fasting morning blood sample | baseline and 12 week | 
| HDL cholesterol | HDL cholesterol measured in a fasting morning blood sample | baseline and 12 week | 
| Triglycerides | Triglycerides measured in a fasting morning blood sample | baseline and 12 week | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
UTI, Type 2 Diabetes, SGLT2 inhibitors, DPP4 inhibitors