Clinical trial NCT04088461: Effect of Linagliptin + Metformin on Patients Who do Not Achieve Normoglucemia With Metformine
Official title: Effect of Linagliptin + Metformin on Glucose Metabolism and Pancreatic Beta Cell Function in Patients With Prediabetes Who do Not Achieve Normoglycemia After 12 Months of Treatment With Metformin Alone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Prediabetic State
Impaired Glucose Tolerance
Insulin Resistance
Keywords: Prediabetes
Insulin resistance
hyperglucemia
Lead sponsor: Universidad de Guanajuato
Sponsor class: OTHER
Collaborators: name: Hospital Regional de Alta Especialidad del Bajio
First posted: 2019-09-12
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Glucose levels during OGTT
timeFrame: 6 months
measure: Pancreatic beta cell function
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: León
country: Mexico
facility: Universidad de Guanajuato
state: Guanajuato
Study officials:
affiliation: Universidad de Guanajuato
name: Rodolfo Guardado Mendoza, MDPhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.