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

Phase 4

Completed

• Conditions: Prediabetic State; Insulin Resistance
• Interventions: Combination Product: Linagliptin + metformin; Drug: Metformin

• Registration Number: NCT03004612
• Lead Sponsor: Universidad de Guanajuato

Brief Summary

Type 2 diabetes is a worldwide epidemic disease, and preventive strategies are needed to face this health problem. The goal of this clinical trial is to evaluate the effect of linagliptin + metformin vs metformin alone on physiopathological parameters, such as glucose metabolism, insulin resistance, insulin secretion and pancreatic beta cell function in patients with impaired fasting glucose plus impaired glucose tolerance, during 24 months.

Detailed Description

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-12-21
• Study First Submitted QC: 2016-12-22
• Study First Posted: 2016-12-29
• Primary Completion: 2019-05
• Study Completion: 2019-06
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-05
• Last Update Posted: 2019-07-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 144

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Linagliptin + Metformin plus lifestyle	Linagliptin + metformin	Patients are randomized to receive for 24 months Linagliptin 2.5mg + metformin 850mg every 12 hours. The start of the dose in this group will be gradual so that at the month of treatment the patient can be with the full doses. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90-150min/week.
Metformin plus lifestyle	Metformin	Patients are randomized to receive for 24 months Metformin 850mg every 12 hours. The start of the dose in this group will be gradual so that at the month of treatment the patient can be with the full doses. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90-150min/week.

Primary Outcome Measures

Name	Time	Method
Change from basal fasting and post2h OGTT glucose levels at 12 and 24 months	12 and 24 months	Fasting and post-2h OGTT glucose values (mg/dl)

Secondary Outcome Measures

Name	Time	Method
Change from basal pancreatic beta cell function at 12 and 24 months	12 and 24 months	Evaluated with the measurements of glucose and insulin during the oral glucose tolerance test; as well as with the glucose and insulin measurements from the hyperglycemic clamp, as the Disposition index.
Incidence of type 2 diabetes	24 months	New reported cases with T2D according the the ADA diagnostic criteria
Change from basal insulin sensitivity at 12 and 24 months	12 and 24 months	Insulin sensitivity evaluated during the oral glucose tolerance test by the Matsuda index, and reported as an arbitrary units.
Change from basal Weight at 12 and 24 months	12 and 24 months	Weight measurement during the study, in kg

Trial Locations

Locations (1)

Universidad de Guanajuato; 🇲🇽 León, Guanajuato, Mexico