Effect of Linagliptin + Metformin on Patients Who do Not Achieve Normoglucemia With Metformine

Randomization and masking. Patients will be randomly assigned in a 1:1 ratio to receive linagliptin/metformin 2.5/850mg every 12 h + lifestyle modification program, or metformin 850mg every 12 h + lifestyle modification program during 6 months. Randomization will be performed using an electronic random numbers table by a Nutritionist not involved in the study. Participants and investigators involved in the patients follow-up and outcome measurements will be masked to treatment allocation during the entire study.

Patients will have a follow-up visit every month. Every appointment is about 30-45 minutes; medications tolerance and side effects will be recorded in every patients´ visit. Nutritional and physical activity assessment according to the patient´s weight will be performed by a Nutritionist every month. Monthly adherence to medications will be evaluated by pill counting; nutritional adherence and energy intake will be evaluated at 6 months by a food frequency questionnaire, and physical activity at 0 and 6 months. At basal and at 6 months patients will have an OGTT. Primary objective is to evaluate at 6 months glucose profile during OGTT, insulin secretion and pancreatic β-cell function by the OGTT DI, and regression to normoglycemia; T2D will be diagnosed and confirmed by at least two consecutive measurements of the same criteria: glycated haemoglobin ≥ 6.5 %, fasting glucose ≥ 126mg/dl, or 2 h glucose ≥ 200 mg/dl.

Inclusion criteria

• Patients with impaired glucose tolerance (2 h glucose between 140 - 199 mg / dL) that after 1 year of treatment with metformin at a dose of 1700 mg daily + lifestyle modifications don't achieve normoglycemia.
• Patients who accept to participate in the study and sign informed consent.

Exclusion criteria

• Patients with type 2 Diabetes diagnosted previuosly or detected during the OGTT
• Serum creatinine > 1.6 mg/dL
• Hypertriglyceridemia very high (>500 mg/dL)
• Pregnancy
• Systolic blood pressure > 180 mmHg or Diastolic blood pressure >105 mmHg (patients could be re-screened after blood pressure control)
• Excessive alcohol intake, acute or chronic
• Medications or medical conditions that affect glucose homeostasis (thiazides, beta blockers, glucocorticoids for systemic use, weight-reducing drugs or anorexigenics, Cushing's syndrom, Thyrotoxicosis.