Study design and patient selection
liver dysfunction, coronary or cerebrovascular), ASCVD, gangrene, liver cirrhosis, T2DM, substance abuse, diabetes
TYPE 1 DIABETES MELLITUS, LEG ULCERS, DISEASE, GANGRENE, LIVER CIRRHOSIS, ATHEROSCLEROTIC CARDIOVASCULAR DISEASE, CONGESTIVE HEART FAILURE, EVENTS, ASCVD, PROLIFERATIVE RETINOPATHY, DIABETES
The study was a randomized, open, parallel group intervention study conducted based on data collected as a participating center in the multicenter clinical trial TOSCA.IT (Thiazolidinediones Or Sulphonylureas and Cardiovascular Accidents. Intervention Trial; NCT00700856, The study protocol was approved by the Ethics Review Committee/Institutional Review Board of the Coordinating Center and by the Ethics Committees of each individual participating center. The study complies with the Declaration of Helsinki and the EU guidelines on Good Clinical Practice for conducting clinical trials of medicines. Informed consents were signed by each patient in the pre-randomization phase; to each participant was clearly explained the right to abandon the project at any time and for any reason, without any kind of consequence.The inclusion criteria considered for the selection of patients in the study were (details in (The exclusion criteria considered were: patients diagnosed with Type 1 Diabetes Mellitus; therapy with thiazolidinediones within 6 months prior to the start of the study; contraindications or documented intolerance to metformin, pioglitazone or glimepiride; documented presence of cardiovascular events (coronary or cerebrovascular) occurring in the 3 months preceding the start of the study; proliferative retinopathy; plasma creatinine values >1.5 mg/dL; presence of documented congestive heart failure (NYHA class 1 or higher); chronic use of corticosteroid drugs; presence of leg ulcers or gangrene; documented presence of liver cirrhosis or severe liver dysfunction (ALT values > 2.5 times the normal cut-off); pregnancy or breastfeeding; documented presence of oncological disease; substance abuse; presence of any other condition not previously mentioned that could interfere with adherence to therapy or cause serious harm to the patient.Seventy-three patients with T2DM attending the U.O.C. of Diabetology and Dietetics of Ulss 6 Euganea, Padova (Italy) fulfilling the inclusion criteria were recruited and subsequently randomized into two arms of the study, characterized by different treatment regimens:1) metformin 2 g/day, with the addition of pioglitazone (thiazolidinedione), at a dosage of 15 mg/day;2) metformin 2 g/day, with the addition of glimepiride (sulfonylurea) at a dosage of 2 mg/day.Clinical and laboratory parameters were measured at the randomization visit and at the follow-up visit after 5 years of treatment. For each patient, the following anthropometric, clinical and haemato-chemical parameters were investigated: age, duration of diabetes, height, weight, BMI, waist circumference, diastolic and systolic blood pressure, serum creatinine and eGFR, glycated haemoglobin (HbA1c), serum C-reactive protein (CRP), AGE, s-RAGE, and AGE/s-RAGE. Basal 10-year ASCVD (Atherosclerotic Cardiovascular Disease) risk was calculated according to 