Clinical trial NCT04134650: Effect of Low Dose Combination of Linagliptin + Metformin to Prevent Diabetes
Official title: Effect of Low Dose Combination of Linagliptin and Metformin to Improve Pancreatic Beta Cell Function, Insulin Resistance and Cardiovascular Function in Patients With Prediabetes and Overweight/Obesity: Randomizer Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Prediabetic State
Insulin Resistance
Keywords: Prediabetes
Lead sponsor: Universidad de Guanajuato
Sponsor class: OTHER
Collaborators: name: Hospital Regional de Alta Especialidad del Bajio
First posted: 2019-10-22
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 ratio allocation
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Change from basal fasting and 2 hours glucose levels during the oral glucose tolerance test at 12 months
timeFrame: 12 months
Secondary outcomes:
measure: Change from basal pancreatic beta cell function at 12 months
timeFrame: 12 months
measure: Change from basal insulin sensitivity at 12 months
timeFrame: 12 months
Other outcomes:
Locations:
city: León
country: Mexico
facility: Universidad de Guanajuato
state: Guanauato
Study officials:
affiliation: Universidad de Guanajuato
name: Rodolfo Guardado-Mendoza, MDPhD
role: PRINCIPAL_INVESTIGATOR
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