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

Study Overview
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Brief Summary
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The goal of this protocol is to evaluate the effect of addhing linagliptin to patients with prediabetes who do not reverse to normoglycemia after 12 months of treatment with metformin alone. The duration of the study will be 6 months, and it is primarily a efficacy study. Main outcomes will be glucose levels during OGTT, insulin secretion and pancreatic beta cell function measured by the disposition index derived from the OGTT.

Detailed Description
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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.

Official Title
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Effect of Linagliptin + Metformin on Glucose Metabolism and Pancreatic Beta Cell Function in Patients With Prediabetes Who do Not Achieve Normoglycemia After 12 Months of Treatment With Metformin Alone

Conditions
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Prediabetic State, Impaired Glucose Tolerance, Insulin Resistance

Intervention / Treatment
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* Drug: Linagliptin / Metformin Oral Tablet
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Linagliptin + Metformin and lifestyle<br>Patients with impaired glucose tolerance randomly assigned to linagliptin 2.5 mg + metftormin 850 mg every 12 hours during 6 months. | Drug: Linagliptin / Metformin Oral Tablet<br>* Linagliptin 2.5 mg + Metformin 850 mg twice daily plus a lifestyle modifications program<br>* Other names: Combined treatment;|
| Active Comparator: Metformin<br>Patients with impaired glucose tolerance randomly assigned to metftormin 850 mg every 12 hours during 6 months. | Drug: Metformin<br>* Metformin 850 mg twice daily plus lifestyle modifications program<br>* Other names: Metformin alone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose levels during OGTT | Glucose levels during OGTT | 6 months | 
| Pancreatic beta cell function | Pancreatic beta cell function measured with the disposition index during OGTT | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prediabetes, Insulin resistance, hyperglucemia