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

Sponsor

Universidad de Guanajuato (Other)

Overall Status

Completed

CT.gov ID

NCT03004612

Collaborator

Hospital Regional de Alta Especialidad del Bajio (Other)

144

Enrollment

Location

Arms

Duration (Months)

3.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prediabetic State Insulin Resistance	Combination Product: Linagliptin + metformin Drug: Metformin	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Jan 1, 2016

Actual Primary Completion Date :

May 1, 2019

Actual Study Completion Date :

Jun 1, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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.
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
Incidence of type 2 diabetes [24 months]
New reported cases with T2D according the the ADA diagnostic criteria

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.