Effect of Linagliptin + Metformin vs Metformin Alone in Patients With Prediabetes

The main goal of this clinical trial is to compare the effect of two different treatments during 24 months:

• Lifestyle modification program + metformin 850mg twice daily
• Lifestyle modification program + linagliptin (2.5mg) and metformin (850mg) twice daily

on the following parameters, after 24 months of treatment:

• Glucose metabolism, evaluated by the oral glucose tolerance
• Insulin resistance, evaluated by the oral glucose tolerance in 100% of the patients and by hyperglycemic clamp in 10 % of the patients
• Insulin secretion, evaluated by the oral glucose tolerance in 100% of the patients and by hyperglycemic clamp in 10 % of the patients
• Pancreatic beta cell function, evaluated by the oral glucose tolerance in 100% of the patients and by hyperglycemic clamp in 10 % of the patients
• 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.

Inclusion criteria

• Patients with prediabetes, defined for the existence impaired glucose tolerance (Glucose between 140 and 199 mg/dL at the 2 hours of the Oral Glucose Tolerance test (OGTT) ) with or without impaired fasting glucose (Fasting glucose between 100 and 125 mg/dL)
• Patients who accept to participate in the study and sign the informed consent letter.

Exclusion criteria

• Patients with diagnosed Type 2 Diabetes Mellitus previously or detected during the OGTT
• Patients in actual treatment or during the last 3 months with metformin, pioglitazone or another antidiabetic drug, including insulin.
• Serum creatinine > 1.6 mg/dL
• Hypertriglyceridemia very high (>500 mg/dL)
• Pregnant women
• Altered arterial hypertension (Systolic > 180 mmHg or Diastolic >105 mmHg)
• 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 syndrome, Thyrotoxicosis.