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

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

Inclusion Criteria:

• DMT2 patients were enrolled in presence of

  1. Age >35 and <75 years old
  2. Uncontrolled diabetes during treatment (glycosylated hemoglobin (HbA1c) > 75 mmol/mol )
  3. Combined therapy at least by 6 months.

Exclusion Criteria:

1. HbA1c < 75 mmol/mol (9%);
2. 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;
3. Estimated glomerular filtration rate (GFR) <30 ml/min (according to MDRD formula)
4. .Liver Failure
5. Recent history of Heart stroke, systemic infections, dehydration, lactic acidosis
6. Heart failure (NYHA I - IV)
7. Active bladder cancer or history of bladder cancer
8. macroscopic haematuria of unidentified nature
9. hypersensitivity to drug used (metformin, alogliptin, pioglitazone)
10. breastfeeding