Gliflozins and Cardiovascular Risk Factors in Type 2 Diabetes (GIOIA)

Study Overview
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Brief Summary
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GIOIA represents a multicenter pragmatic prospective cohort study, aimed at evaluating the effects of SGLT2 inhibitors currently marketed (dapagliflozin, canagliflozin, empagliflozin) on markers of vascular, myocardial and renal damage, in patients with type 2 diabetes not well controlled with metformin and/or basal insulin. The changes of the interest outcomes are compared with those obtained with a comparator glucose lowering class (DPP-4inhibitors) over a follow-up of two years.

Official Title
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Effects of Gliflozins on Markers of Cardiovascular Risk in Type 2 Diabetes (GIOIA): a Multicenter Pragmatic Prospective Cohort Study

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: SGLT-2i
* Drug: DPP-4i


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: type 2 diabetes for at least 5 years new use of an SGLT2-I or DPP4-I as add-on to metformin or insulin according to clinical practice HbA1c levels ≥ 7% and ≤ 8.5% eGFR ≥ 60 ml/min/1.73 m2 Exclusion Criteria: Type 1 diabetes or secondary diabetes resulting from specific causes History of neurovascular ulcers Previous therapy with SGLT-2i or DPP4-i in the 3 months prior to the study enrollment History of cancer within the last 5 years Pregnancy or active breast-feeding Serum creatinine level ≥ 1.3 mg/dl in women and ≥ 1.4 mg/dl in men eGFR ≤ 60 ml/min/1.73 m2

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SGLT-2i<br>Type 2 diabetic patients treated with metformin and/or insulin starting therapy with a SGLT-2 inhibitor: dapagliflozin 10 mg, oral, once daily or canagliflozin 100 mg, oral, daily or empagliflozin 10 mg, oral, daily | Drug: SGLT-2i<br>* Dapagliflozin or canagliflozin or empagliflozin add on to metformin ± basal insulin<br>|
| DPP-4i<br>Type 2 diabetic patients treated with metformin and/or insulin starting therapy with a DPP-4 inhibitor: sitagliptin 100 mg, oral once daily or vildagliptin 50 mg, oral, twice daily or saxaglitpin 5 mg, oral, once daily or linagliptin 5 mg, oral, once daily or alogliptin 25 mg, oral, once daily | Drug: DPP-4i<br>* Sitagliptin or vildagliptin or saxagliptin or linagliptin or alogliptin add on to metformin ± basal insulin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Carotid intima-media thickness (CIMT) | Progression (increase in mean CIMT in millimeters [mm]) or regression (reduction > o = 0.020 mm on mean CIMT) after 2 years of follow-up | 24 months | 
| Myocardial stiffness indexes | Change from baseline in: Left Ventricular Ejection Fraction (LVEF) in percentage (%), Diastolic Left Ventricular Dimension (LVDs) in centimeters (cm) Interventricular Septum thickness (IVS) in cm left vetricular posterior wall thickness (PWs) in cm | 24 months | 
| Urinary albumin to creatinine ratio excretion | Development of microalbuminuria in normoalbuminuric patients at baseline or development of macroalbuminuria in patients with microalbuminuria at baseline; regression of microalbuminuria to normoalbuminuria or regression of macroalbuminuria to microalbuminuria | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight | Change in body weight in kilograms (kg) from baseline | 24 months | 
| Body mass index (BMI) | Change in body mass index in Kg/mq from baseline | 24 months | 
| Waist circumference (WC) | Change in waist circumference in cm from baseline | 24 months | 
| Blood pressure | Change in systolic and dyastolic blood pressure in mmHg from baseline | 24 months | 
| estimated Glomerular filtration rate (eGFR) | Change in estimated glomerular filtration rate in mI/min/1.73 mq from baseline | 24 months |