Clinical trial NCT04131582: Effect of Empagliflozin + Linagliptin + Metformin + Lifestyle in Patients With Prediabetes
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
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: 2019-10-18
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
Primary purpose: PREVENTION

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

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 850 mg twice daily
2. 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

1) 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from basal fasting and post2h OGTT glucose levels at 6 and 12 months
timeFrame: 6 and 12 months
Secondary outcomes:
measure: Change from basal pancreatic beta cell function at 6 and 12 months
timeFrame: 6 and 12 months
measure: Change from basal insulin sensitivity at 6 and 12 months
timeFrame: 6 and 12 months
measure: Change from basal Weight at 6 and 12 months
timeFrame: 6 and 12 months
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
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