A Randomized, Double-Blind Trial Comparing the Efficacy and Safety of Fenofibrate, Metformin, Their Combination and Placebo in Patients With Metabolic Syndrome.

Inclusion criteria

• Male or female patients aged from 18 to 75 years old (at inclusion V1).
• With 3 of the following 5 criteria, including at least 2 biochemical abnormalities (glucose and one lipid abnormality)
• And having signed a written informed consent (at inclusion V1).

Exclusion criteria

• known Type 1 diabetes, or treated type 2 diabetes [25], [26];
• wth HbA1c > 8 % [27] at the first blood sample;
• body mass index (BMI) > 45 kg/m2;
• females who were not surgically sterilized or not using adequate contraceptive or not using adequate contraceptive precautions or not postmenopausal
• pregnant or lactating women;
• known hypersensitivity to fibrates;
• known hypersensitivity to metformin chlorhydrate; known abnormal thyroid hormone levels, or high thyroid stimulating hormone (TSH) level;
• having received an investigational drug in the last 30 days before the date of randomization;
• unable or unwilling to comply with the protocol;
• likely to withdraw from the study before its completion;
• treated with some concomitant medications:
• reporting a change within the last 6 weeks before randomization and during the study in the medications that could interfere with the lipid profile (i.e., anti-hypertensive drugs, oral corticosteroids, thyroid hormones, retinoids, thiazidic derivatives, hormone replacement therapies);
• presenting with the following disease or conditions:

• chronic respiratory insufficiency, patient with medical device for sleep apnea;
• current chronic pancreatitis, or identified risk or known history of acute pancreatitis;
• hepatic insufficiency, acute alcohol intoxication, alcoholism;
• known cholelithiasis without cholecystectomy;
• aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2 times the upper limit normal (ULN);
• musculoskeletal disease or increased creatine phosphokinase (CPK) > 3 times the ULN;
• renal failure or renal dysfunction defined by serum creatinine levels > 135 μmol/L in males and > 110 μmol/L in females [28];
• acute conditions with the potential to alter renal function such as dehydration, severe infection, shock or intravascular administration of iodinated contrast agents;
• acute or chronic disease which may cause tissue hypoxia such as cardiac or respiratory failure, recent myocardial infarction (within 3 months prior to randomization), shock;
• known gastric or peptic ulcer or intestinal disease within the previous 3 months of randomization capable of modifying the intestinal absorption of the drugs;
• any other severe pathology such as cancer, mental illness, etc., which in the opinion of the investigator might pose a risk to the patient or confound the results of the study