4T: Effect of Empagliflozin + Linagliptin + Metformin + Lifestyle in Patients With Prediabetes

Sponsor

Universidad de Guanajuato (Other)

Overall Status

Unknown status

CT.gov ID

NCT04131582

Collaborator

Hospital Regional de Alta Especialidad del Bajio (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.1

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 trial is to evaluate the effect of empagliflozin + linagliptin + metformin + lifestyle on physiopathological parameters, sush as glucose metabolism, insulin resistance, pancreatic beta cell function and cardiovascular function in patients with impaired fasting glucose plus impaired glucose tolerance, during 12 months

Condition or Disease	Intervention/Treatment	Phase
Prediabetic State Insulin Resistance	Combination Product: Linagliptin + metformin and Empagliflozin + metformin Drug: Metformin	Phase 3

Detailed Description

The main goal of this clinical trial is to compare the effect of two different treatments during 12 months:

Lifestyle modification program + metformin 850 mg twice daily
Lifestyle modification program empagliflozin (12.5 mg) + metformin (850 mg) once daily plus linagliptin (2.5 mg) + metformin (850 mg) once daily On the following parameters, after 12 months of treatment

Glucose metabolism, evaluated by oral glucose tolerance test 2) Insulin resistance evaluated by the oral glucose tolerance 3) Insulin secretion, evaluated by the oral glucose tolerance 4) Pancreatic beta cell function, evaluated by the oral glucose tolerance test 5) Cardiovascular function, evaluated by standard echocardiography by left ventricular ejection fraction

All the patients will have a basal evaluation with an oral glucose tolerance test, lipid profile and body composition measurement by dual energy X-ray absorptiometry (DEXA). After the basal evaluation, if the patients results with impaired fasting glucose and impaired glucose tolerance, 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, and every 6 months an OGTT. After 12 months , patients will repeat the same evaluation performed at basal.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Masking Description:

Assigned treatments will be delivered to the patients in identical envelopes by a person not involved in the trial; persons who evaluate the follow-up and outcomes will be masked to the treatment allocation

Primary Purpose:

Prevention

Official Title:

Effect of a Quadruple Therapy on Pancreatic Islet Function, Insulin Resistance and Cardiovascular Function in Patients With Mixed Prediabetes and Obesity: Randomized Clinical Trial

Actual Study Start Date :

Sep 1, 2019

Anticipated Primary Completion Date :

Dec 15, 2020

Anticipated Study Completion Date :

Dec 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Empagliflozin + linagliptin + metformin plus lifestyle Patients are randomized to receive for 12 months Linagliptin 2.5 mg + metformin 850 mg every 12 hours and empagliflozin 12.5 mg + metformin 850 mg 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 90/150 min/week	Combination Product: Linagliptin + metformin and Empagliflozin + metformin Linagliptin-Metformin 2.5/850mg once daily, Empagliflozin-Metformin 12.5/850mg one daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling Other Names: Trayenta Duo + Jardianz Duo
Active Comparator: Metformin plus lifestyle Patients are randomized to receive for 12 months Metformin 850 mg 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 complete dose. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90/150 min/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: Empagliflozin + linagliptin + metformin plus lifestyle

Patients are randomized to receive for 12 months Linagliptin 2.5 mg + metformin 850 mg every 12 hours and empagliflozin 12.5 mg + metformin 850 mg 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 90/150 min/week

Combination Product: Linagliptin + metformin and Empagliflozin + metformin

Linagliptin-Metformin 2.5/850mg once daily, Empagliflozin-Metformin 12.5/850mg one daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling

Other Names:

Trayenta Duo + Jardianz Duo

Active Comparator: Metformin plus lifestyle

Patients are randomized to receive for 12 months Metformin 850 mg 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 complete dose. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90/150 min/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 6 and 12 months [6 and 12 months]
Fasting and post-2h OGTT glucose values (mg/dl)

Secondary Outcome Measures

Change from basal pancreatic beta cell function at 6 and 12 months [6 and 12 months]
Evaluated with the measurements of glucose and insulin during the oral glucose tolerance
Change from basal insulin sensitivity at 6 and 12 months [6 and 12 months]
Insulin sensitivity evaluated during the oral glucose tolerance test by Matsuda index
Change from basal Weight at 6 and 12 months [6 and 12 months]
Weight measurement during the study, in kg

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 Tolerance Glucose Test (OGTT) with 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 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