Substitution of Sulfonylureas With New Generation of Hypoglycemic Drugs for the Treatment of Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This is a multicentric, prospective, parallel groups study. Patient recruitment will be carried out at the U.O. Departmental Endocrinology and Diabetology ASST FBF Sacco, Fatebenefratelli and Ophthalmic Hospital, and at the SSD of Endocrine Diseases and Diabetology ASST FBF Sacco, L. Sacco Hospital. At the screening visit, patients being treated with sulfonylureas / glinids will be shifted, depending on the subject's biochemical and phenotypic characteristics, based on current prescribing criteria and diabetes complications, to one of 4 different types of treatment: GROUP 1: SGLT2 inhibitors +/- Metformin GROUP 2: DPP4 inhibitors +/- Metformin GROUP 3: GLP1-RA + Long-acting insulin +/- Metformin GROUP 4: SGLT2 inhibitors + DPP4 inhibitors +/- Metformin At the screening visit the clinician will evaluate which new treatment to assign to the patient, based on the subject's biochemical and phenotypic characteristics, current prescribing criteria and existing complications (Algorithm for the treatment of diabetes mellitus, SID-AMD Care Standard 2018)

Detailed Description
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Approximately 500 T2DM patients aged ≥18 years will be enrolled according to the guidelines of the American Diabetes Association (ADA) with poor glycemic control (hemoglobin A1c [A1C] ≥6.5% and ≤11% [≥58 mmol / mol and ≤97 mmol / mol]), in stabilized treatment with sulfonylureas / glinids, which meet all the study enrollment criteria. During the study 7 visits are scheduled which coincide with the routine diabetic visits. During the scheduled visits the patients of the study will be subjected to: Enrollment on the first visit if the inclusion criteria are met and those of exclusion are absent Anamnestic and clinical collection Evaluation of the type of treatment to which they have been assigned and possible modification of drug therapy in the in case that the desired glycemic target has not yet been reached up.

Official Title
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Prospective, Parallel Goups Study, Aimed to Evaluating Possible Benefits of the Treatment of New Generation Hypoglycaemic Drugs Compared to Sulphonylureas for the Tratment of Type 2 Diabetes Mellitus

Conditions
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T2DM (Type 2 Diabetes Mellitus), Diet, Healthy, Renal Function Disorder, Albuminuria

Intervention / Treatment
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* Drug: Sulfa-zero: possible benefits of the treatment of new generation hypoglycaemic drugs compared to sulphonylureas


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age over 18 years; 6.5% <HbA1c <11%; Diagnosis of type 2 diabetes mellitus; Active treatment with sulfonylureas / glinids, both in monotherapy and in association with other long-acting hypoglycemic / insulins. Written informed consent of the patient or a legal guardian signed and dated Exclusion Criteria: Patients suffering from severe systemic diseases, fever, known chronic inflammatory states PCR determinants> 10 mg/L; HbA1c> 11% or HbA1c <6.5%; Use of corticosteroids at the time of enrollment; Poor patient understanding of spoken and written Italian; Absent compliance.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>SGLT2 inibitori +/- Metformin | Drug: Sulfa-zero: possible benefits of the treatment of new generation hypoglycaemic drugs compared to sulphonylureas<br>* Substitution of sulfonylureas with other classes of new hypoglycaemic drugs. In every group, it will be evaluated: efficacy in terms of glycometabolic compensation (glycemia, HbA1c, lipid profile); effects on BMI, blood pressure monitoring and hypoglycemic risk; changes in renal function and microalbuminuria; tolerability and side effects of the new therapeutic regimes; therapeutic adherence; post-prandial glycemic excursion, determined by a 6-point glycemic diary (pre- and 2h post-prandial glucose values) to be performed at home in the week before the scheduled follow-up visit; effects on chronic complications of diabetes and cardiovascular safety.<br>* Other names: Shift to new generation therapeutic regimens;|
| Group 2<br>DPP4 inibitori +/- Metformin | Drug: Sulfa-zero: possible benefits of the treatment of new generation hypoglycaemic drugs compared to sulphonylureas<br>* Substitution of sulfonylureas with other classes of new hypoglycaemic drugs. In every group, it will be evaluated: efficacy in terms of glycometabolic compensation (glycemia, HbA1c, lipid profile); effects on BMI, blood pressure monitoring and hypoglycemic risk; changes in renal function and microalbuminuria; tolerability and side effects of the new therapeutic regimes; therapeutic adherence; post-prandial glycemic excursion, determined by a 6-point glycemic diary (pre- and 2h post-prandial glucose values) to be performed at home in the week before the scheduled follow-up visit; effects on chronic complications of diabetes and cardiovascular safety.<br>* Other names: Shift to new generation therapeutic regimens;|
| Group 3<br>GLP1-RA + Long-Acting Insulin +/- Metformin | Drug: Sulfa-zero: possible benefits of the treatment of new generation hypoglycaemic drugs compared to sulphonylureas<br>* Substitution of sulfonylureas with other classes of new hypoglycaemic drugs. In every group, it will be evaluated: efficacy in terms of glycometabolic compensation (glycemia, HbA1c, lipid profile); effects on BMI, blood pressure monitoring and hypoglycemic risk; changes in renal function and microalbuminuria; tolerability and side effects of the new therapeutic regimes; therapeutic adherence; post-prandial glycemic excursion, determined by a 6-point glycemic diary (pre- and 2h post-prandial glucose values) to be performed at home in the week before the scheduled follow-up visit; effects on chronic complications of diabetes and cardiovascular safety.<br>* Other names: Shift to new generation therapeutic regimens;|
| Group 4<br>SGLT2 inibitori + DPP4 inibitori +/- Metformin | Drug: Sulfa-zero: possible benefits of the treatment of new generation hypoglycaemic drugs compared to sulphonylureas<br>* Substitution of sulfonylureas with other classes of new hypoglycaemic drugs. In every group, it will be evaluated: efficacy in terms of glycometabolic compensation (glycemia, HbA1c, lipid profile); effects on BMI, blood pressure monitoring and hypoglycemic risk; changes in renal function and microalbuminuria; tolerability and side effects of the new therapeutic regimes; therapeutic adherence; post-prandial glycemic excursion, determined by a 6-point glycemic diary (pre- and 2h post-prandial glucose values) to be performed at home in the week before the scheduled follow-up visit; effects on chronic complications of diabetes and cardiovascular safety.<br>* Other names: Shift to new generation therapeutic regimens;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of the glyco-metabolic parameters | Evaluation of the new generation hypoglicemic drugs on Hba1c, blood glucose, lipidic profile | 12 months | 
| Therapeutic adherence | Assessment of adherence to the doctor's prescription of new generation hypoglycaemic drugs | 12 months | 
| Long-term diabetes complications | Evaluation of the effect of new generation hypoglycemic drugs on the long-term complications of diabetes compared to the effect obtained with sulphonylureas | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Values of the insulin-sensitivity | Evaluation of the effect of new generation hypoglycemic drugs on the insulin secretion of diabetes compared to the effect obtained with sulphonylureas. | 12 months | 
| Therapeutic compliance, even in populations over 70 years. | Evaluation of the effect of new generation hypoglycemic drugs on therapeutic adherence with respect to the effect obtained with sulphonylureas even in older subjects. | 12 months | 
| Insulin parameters after shift to new-generation hypoglycaemic therapeutic regimens | HOMA-IR and HOMA-B% insulin parameters evaluation in patients not in insulin treatment | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sulfaniluree/glinidi