Effect of Low Dose Combination of Linagliptin + Metformin to Prevent Diabetes

NCT ID: NCT04134650

Last Updated: 2019-10-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-01
• Study Completion Date: 2020-07-01

Brief Summary

Type 2 diabetes is a chronic disease that has reached global epidemic proportions due to the growing number of patients in all countries; It has become the disease that causes more chronic and acute complications to patients, unfortunately, when the diagnosis of type 2 diabetes is made patients are identified at very advanced stages of the disease.

For all the above, the best strategies will be those that are aimed at early stages of the disease, and the investigators are convinced that the use the combination of drugs with additive pathophysiological effect plus cardiovascular protection in early stages, will have better results, lasting and with greater results impact on the natural history of the disease that throws measures that may have an applicability in clinical practice, in order to contribute to the control of this pathology. Therefore, the combination of medications with different mechanisms of action, in low doses, could be a useful strategy not only to prevent type 2 diabetes, but also to prevent macro and microvascular complications early. The goal of this clinical trial is to evaluate the effect of low doses 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 12 months.

Detailed Description

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

1. Lifestyle modification program + metformin 1700mg every 24 hours.

2. Lifestyle modification program + linagliptin (2.5mg) and metformin (1700mg) every 24 hours.

on the following parameters, after 12 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

3. Insulin secretion, evaluated by the oral glucose tolerance in 100% of the patients

4. Pancreatic beta cell function, evaluated by the oral glucose tolerance in 100% of the patients

5. Cardiovascular function, evaluated by ejection fraction measurement, diastolic and systolic preloads measured by standard echocardiography.

All the patients will have a basal evaluation with an oral glucose tolerance test, lipid profile, body composition. After the basal evaluation, if the patients result with prediabetes (FASTING IMPAIRED GLUCOSE/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. After 6 months, patients will repeat the same evaluation performed as the basal evaluation.

Conditions

Prediabetic State; Insulin Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Linagliptin + Metformin plus lifestyle

Patients are randomized to receive for 12 months Linagliptin 2.5mg + metformin 1700mg every 24 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.

Group Type: EXPERIMENTAL

Linagliptin + metformin

Intervention Type: COMBINATION_PRODUCT

Linagliptin-Metformin 2.5/1700mg daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling

Metformin plus lifestyle

Patients are randomized to receive for 12 months Metformin 1700mg every 24 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.

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Metformin 1700mg daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling

Interventions

Linagliptin + metformin

Linagliptin-Metformin 2.5/1700mg daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling

Intervention Type: COMBINATION_PRODUCT

Metformin

Metformin 1700mg daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling

Intervention Type: DRUG

Other Intervention Names

low doses of Linagliptin + metformin

Eligibility Criteria

Inclusion Criteria

• Patients with prediabetes, defined for the existence of one or both of the following conditions: 1) impaired fasting glucose (Fasting glucose between 100 and 125 mg/dL), 2) impaired glucose tolerance (Glucose between 140 and 199 mg/dL at the 2 hours of the Oral Glucose Tolerance test (OGTT)
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Regional de Alta Especialidad del Bajio

OTHER

Sponsor Role: collaborator

Universidad de Guanajuato

OTHER

Sponsor Role: lead

Responsible Party

Rodolfo Guardado Mendoza

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rodolfo Guardado-Mendoza, MDPhD

Role: PRINCIPAL_INVESTIGATOR

Universidad de Guanajuato

Locations

Universidad de Guanajuato

León, Guanauato, Mexico

Site Status: RECRUITING

Countries

Mexico

Central Contacts

Rodolfo Guardado-Mendoza, MDPhD

Role: CONTACT

guardamen@gmail.com

011524772672000 ext. 1701

Facility Contacts

Rodolfo Guardado-Mendoza, MDPhD

Role: primary

guardamen@gmail.com

4772674900 ext. 3683

Elizabeth Rodríguez-Guzmán, MD

Role: backup

elirodg@hotmail.com

4772674900 ext. 3683

References

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Reference Type: BACKGROUND

PMID: 16873794 (View on PubMed)

DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care. 1992 Mar;15(3):318-68. doi: 10.2337/diacare.15.3.318.

Reference Type: BACKGROUND

PMID: 1532777 (View on PubMed)

Faerch K, Borch-Johnsen K, Holst JJ, Vaag A. Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes? Diabetologia. 2009 Sep;52(9):1714-23. doi: 10.1007/s00125-009-1443-3. Epub 2009 Jul 10.

Reference Type: BACKGROUND

PMID: 19590846 (View on PubMed)

Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577-80. doi: 10.1177/29.4.6166661.

Reference Type: RESULT

PMID: 6166661 (View on PubMed)

King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998 Sep;21(9):1414-31. doi: 10.2337/diacare.21.9.1414.

Reference Type: RESULT

PMID: 9727886 (View on PubMed)

Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998 Jul 23;339(4):229-34. doi: 10.1056/NEJM199807233390404.

Reference Type: RESULT

PMID: 9673301 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CI/HRAEB/2018/0018

Identifier Type: -

Identifier Source: org_study_id