Effect of Linagliptin + Metformin vs Metformin Alone in Patients With Prediabetes (PRELLIM)

July 5, 2019 updated by: Rodolfo Guardado Mendoza, Universidad de Guanajuato

Effect 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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

144

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Guanajuato
      • León, Guanajuato, Mexico, 37670
        • Universidad de Guanajuato

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Linagliptin + Metformin plus lifestyle
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.
Combination product: Linagliptin + metformin
Linagliptin-Metformin 2.5/850mg twice daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling
Other Names:
  • Tradjenta Duo
Active Comparator: Metformin plus lifestyle
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.
Drug: Metformin
Metformin 850mg twice daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from basal fasting and post2h OGTT glucose levels at 12 and 24 months
Time Frame: 12 and 24 months
Fasting and post-2h OGTT glucose values (mg/dl)
12 and 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from basal pancreatic beta cell function at 12 and 24 months
Time Frame: 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.
12 and 24 months
Change from basal insulin sensitivity at 12 and 24 months
Time Frame: 12 and 24 months
Insulin sensitivity evaluated during the oral glucose tolerance test by the Matsuda index, and reported as an arbitrary units.
12 and 24 months
Change from basal Weight at 12 and 24 months
Time Frame: 12 and 24 months
Weight measurement during the study, in kg
12 and 24 months
Incidence of type 2 diabetes
Time Frame: 24 months
New reported cases with T2D according the the ADA diagnostic criteria
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidad de Guanajuato

Collaborators

Hospital Regional de Alta Especialidad del Bajio

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2016

Primary Completion (Actual)

May 1, 2019

Study Completion (Actual)

June 1, 2019

Study Registration Dates

First Submitted

December 21, 2016

First Submitted That Met QC Criteria

December 22, 2016

First Posted (Estimate)

December 29, 2016

Study Record Updates

Last Update Posted (Actual)

July 9, 2019

Last Update Submitted That Met QC Criteria

July 5, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CEI-22-16

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Insulin Resistance

Clinical Trials on Metformin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Peru

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe