Effect of Linagliptin + Metformin on Patients Who do Not Achieve Normoglucemia With Metformine

NCT ID: NCT04088461

Last Updated: 2019-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2018-09-30

Brief Summary

The goal of this protocol is to evaluate the effect of addhing linagliptin to patients with prediabetes who do not reverse to normoglycemia after 12 months of treatment with metformin alone. The duration of the study will be 6 months, and it is primarily a efficacy study. Main outcomes will be glucose levels during OGTT, insulin secretion and pancreatic beta cell function measured by the disposition index derived from the OGTT.

Detailed Description

Randomization and masking. Patients will be randomly assigned in a 1:1 ratio to receive linagliptin/metformin 2.5/850mg every 12 h + lifestyle modification program, or metformin 850mg every 12 h + lifestyle modification program during 6 months. Randomization will be performed using an electronic random numbers table by a Nutritionist not involved in the study. Participants and investigators involved in the patients follow-up and outcome measurements will be masked to treatment allocation during the entire study.

Patients will have a follow-up visit every month. Every appointment is about 30-45 minutes; medications tolerance and side effects will be recorded in every patients´ visit. Nutritional and physical activity assessment according to the patient´s weight will be performed by a Nutritionist every month. Monthly adherence to medications will be evaluated by pill counting; nutritional adherence and energy intake will be evaluated at 6 months by a food frequency questionnaire, and physical activity at 0 and 6 months. At basal and at 6 months patients will have an OGTT. Primary objective is to evaluate at 6 months glucose profile during OGTT, insulin secretion and pancreatic β-cell function by the OGTT DI, and regression to normoglycemia; T2D will be diagnosed and confirmed by at least two consecutive measurements of the same criteria: glycated haemoglobin ≥ 6.5 %, fasting glucose ≥ 126mg/dl, or 2 h glucose ≥ 200 mg/dl.

Conditions

Prediabetic State; Impaired Glucose Tolerance; Insulin Resistance

Study Design

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

Study Groups

Linagliptin + Metformin and lifestyle

Patients with impaired glucose tolerance randomly assigned to linagliptin 2.5 mg + metftormin 850 mg every 12 hours during 6 months.

Group Type: EXPERIMENTAL

Linagliptin / Metformin Oral Tablet

Intervention Type: DRUG

Linagliptin 2.5 mg + Metformin 850 mg twice daily plus a lifestyle modifications program

Metformin

Patients with impaired glucose tolerance randomly assigned to metftormin 850 mg every 12 hours during 6 months.

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Metformin 850 mg twice daily plus lifestyle modifications program

Interventions

Linagliptin / Metformin Oral Tablet

Linagliptin 2.5 mg + Metformin 850 mg twice daily plus a lifestyle modifications program

Intervention Type: DRUG

Metformin

Metformin 850 mg twice daily plus lifestyle modifications program

Intervention Type: DRUG

Other Intervention Names

Combined treatment; Metformin alone

Eligibility Criteria

Inclusion Criteria

• Patients with impaired glucose tolerance (2 h glucose between 140 - 199 mg / dL) that after 1 year of treatment with metformin at a dose of 1700 mg daily + lifestyle modifications don't achieve normoglycemia.
• Patients who accept to participate in the study and sign informed consent.

Exclusion Criteria

• Patients with type 2 Diabetes diagnosted previuosly or detected during the OGTT
• Serum creatinine > 1.6 mg/dL
• Hypertriglyceridemia very high (>500 mg/dL)
• Pregnancy
• Systolic blood pressure > 180 mmHg or Diastolic blood pressure >105 mmHg (patients could be re-screened after blood pressure control)
• 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 syndrom, 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, Guanajuato, Mexico

Countries

Mexico

References

Alvarez-Canales MFL, Salazar-Lopez SS, Farfan-Vazquez D, Martinez-Lopez YE, Gonzalez-Mena JN, Jimenez-Ceja LM, Vargas-Ortiz K, Evia-Viscarra ML, Montes de Oca-Loyola ML, Folli F, Aguilar-Garcia A, Guardado-Mendoza R. Effect of linagliptin on glucose metabolism and pancreatic beta cell function in patients with persistent prediabetes after metformin and lifestyle. Sci Rep. 2021 Apr 22;11(1):8750. doi: 10.1038/s41598-021-88108-8.

Reference Type: DERIVED

PMID: 33888772 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CEI-35-16

Identifier Type: -

Identifier Source: org_study_id