PRELLIMEffect of Linagliptin + Metformin vs Metformin Alone on the Role of Pancreatic Islet Function, Insulin Resistance and Markers of Cardiovascular Risk in Patients With Prediabetes: Randomized Clinical Trial

The main goal of this clinical trial is to compare the effect of two different treatments during 24 months: 1. Lifestyle modification program + metformin 850mg twice daily 2. Lifestyle modification program + linagliptin (2.5mg) and metformin (850mg) twice daily on the following parameters, after 24 months of treatment: 1. Glucose metabolism, evaluated by the oral glucose tolerance 2. Insulin resistance, evaluated by the oral glucose tolerance in 100% of the patients and by hyperglycemic clamp in 10 % of the patients 3. Insulin secretion, evaluated by the oral glucose tolerance in 100% of the patients and by hyperglycemic clamp in 10 % of the patients 4. Pancreatic beta cell function, evaluated by the oral glucose tolerance in 100% of the patients and by hyperglycemic clamp in 10 % of the patients 5. Systemic inflammation and cardiovascular risk factors, evaluated by cytokines interlelukin-6 (IL6), C-reactive protein (PCR), and measurement of the intima media thickness by ultrasound. All the patients will have a basal evaluation with an oral glucose tolerance test, lipid profile, body composition, and IMT measurement by ultrasonography; and 10 % will be invited for the hyperglycemic clamp. After the basal evaluation, if the patients result with IMPAIRED GLUCOSE TOLERANCE and have at least 2 risk factors, they will be invited to the intervention phase where they will be randomized to one of the two treatment groups. Patients will have a follow-up visit every month to review the adherence to the lifestyle modification program and to the medication. Every 6 months OGTT will be performed on all the patients, and in a subset of patients hyperglycemic clamp will be performed at 0, 6 and 12 months. After 18 and 24 months, patients will repeat the same evaluation performed as the basal evaluation.