Anti-inflammatory Status in DM2 Treated Patients

Study Overview
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Brief Summary
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Diabetes mellitus Type 2 (DMT2) - a progressive insulin secretory defect on the background of insulin resistance - is one of the major risk factors for atherosclerosis, an inflammatory disease of the arterial wall, in which leukocytes and oxidized lipoproteins accumulate leading to formation of fatty streaks and atherosclerotic plaques. Atherosclerosis accounts for more than 600,000 deaths annually in the U.S. mainly due to acute myocardial infarction and stroke. Pharmacological therapy of DMT2 includes several drugs used as monotherapy, although combination therapy between metfomin plus thiazolidinediones (TZD) and/or dipeptidyl-peptidase 4 inhibitors (DPP4I) plus TDZ, may delay atherosclerosis progression even if the molecular mechanisms are not clear. Even if normoglycemia is achieved, DMT2 patients still displayed a higher risk for developing atherosclerosis suggesting that other mechanisms of the inflammatory status are involved

Detailed Description
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Diabetes mellitus Type 2 (DMT2) - a progressive insulin secretory defect on the background of insulin resistance - is one of the major risk factors for atherosclerosis, an inflammatory disease of the arterial wall, in which leukocytes and oxidized lipoproteins accumulate leading to formation of fatty streaks and atherosclerotic plaques. Atherosclerosis accounts for more than 600,000 deaths annually in the U.S. mainly due to acute myocardial infarction and stroke. Pharmacological therapy of DMT2 includes several drugs used as monotherapy, although combination therapy between metfomin plus thiazolidinediones (TZD) and/or dipeptidyl-peptidase 4 inhibitors (DPP4I) plus TDZ, may delay atherosclerosis progression even if the molecular mechanisms are not clear . Even if normoglycemia is achieved, DMT2 patients still displayed a higher risk for developing atherosclerosis suggesting that other mechanisms of the inflammatory status are involved

Official Title
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Comparison of Anti-inflammatory Status Linked to Atherosclerosis Formation/Progression Among Diabetes Mellitus Type 2 Patients Under Combined Pharmacological Therapy

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Metformin / alogliptin Oral Product
* Drug: Metformin / Pioglitazone Pill
* Drug: triple therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DMT2 patients were enrolled in presence of Age >35 and <75 years old Uncontrolled diabetes during treatment (glycosylated hemoglobin (HbA1c) > 75 mmol/mol ) Combined therapy at least by 6 months. Exclusion Criteria: HbA1c < 75 mmol/mol (9%); History of drug abuse or alcohol abuse, averaging more than 30 gm/day (3 drinks per day) in the previous 10 years, or history of alcohol intake averaging greater than 10 gm/day (1 drink per day: 7 drinks per week) in the previous one year; Estimated glomerular filtration rate (GFR) <30 ml/min (according to MDRD formula) .Liver Failure Recent history of Heart stroke, systemic infections, dehydration, lactic acidosis Heart failure (NYHA I - IV) Active bladder cancer or history of bladder cancer macroscopic haematuria of unidentified nature hypersensitivity to drug used (metformin, alogliptin, pioglitazone) breastfeeding

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: single center single blind study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: metformin/alogliptin<br>metformin/alogliptin (850 mg/12.5 mg or 1000 mg/12.5 mg every 12 hours) for 12 months | Drug: Metformin / alogliptin Oral Product<br>* 850 or 1000 mg/ 12.5 mg every 12 hours for 12 months<br>|
| Active Comparator: metformin/pioglitazone<br>metformin/pioglitazone (850 mg/15 mg every 12 hours) for 12 months | Drug: Metformin / Pioglitazone Pill<br>* (850 mg/15 mg every 12 hours) for 12 months<br>|
| Active Comparator: triple therapy<br>metformin/pioglitazone (850 mg/15 mg every 12 hours)+alogliptin (12.5 mg every 12 hours) for 12 months | Drug: Metformin / alogliptin Oral Product<br>* 850 or 1000 mg/ 12.5 mg every 12 hours for 12 months<br>Drug: Metformin / Pioglitazone Pill<br>* (850 mg/15 mg every 12 hours) for 12 months<br>Drug: triple therapy<br>* Metformin / Alogliptin/ Pioglitazone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| inflammatory miRNA | Change from Baseline at 12 months | 12 months | 
| side effects | statistically significant difference (P<0.05) in the development of side effects between the groups, recorded using the Naranjo adverse drug reactions scale | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| body weight | effects of each treatment on body mass index (kg/m^2) (as indirect indexes of systemic inflammation and visceral adiposity). | 12 months | 
| Waist values | effects of each treatment on waist values (cm) (as indirect indexes of systemic inflammation and visceral adiposity). | 12 months | 
| drug interaction | statistically significant difference (P<0.05) in the development of drug-drug interactions, recorded using the DIPS scale | 12 months | 
| Fasting blood glucose | effects of each treatment on fasting blood glucose (mg/dL) (as indexes of glucose metabolism); | 12 months | 
| HbA1c levels | effects of each treatment on HbA1c levels (percent) (as indexes of glucose metabolism); | 12 months | 
| liver function | alanine aminotransferase, aspartate aminotransferase, gamma glutamyl-transpeptidase levels, and total bilirubin levels (expressed as mg/dL) (as indexes of liver function). | 12 months | 
| cell count | effects of each treatment on white blood cell count expressed as cell/mm3 (as direct index of systemic inflammation) | 12 months | 
| lipid metabolism/atheroscelorisis | total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides levels (expressed as mg/dL) (as direct indexes of lipid metabolism and atheroscelorisis). | 12 months |