<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03029390</url>
  </required_header>
  <id_info>
    <org_study_id>BM-Prediabetes</org_study_id>
    <nct_id>NCT03029390</nct_id>
  </id_info>
  <brief_title>Effect of Berberine Versus Metformin on Glycemic Control, Insulin Sensitivity and Insulin Secretion in Prediabetes</brief_title>
  <official_title>Effect of Administration of Berberine Versus Metformin on Glycemic Control, Insulin Sensitivity and Insulin Secretion in Patients With Prediabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Guadalajara</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Guadalajara</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pre diabetes (PD) is a term that refers to alterations in glucose homeostasis, including&#xD;
      impaired fasting glucose (IFG), Imparied glucose tolerance (IGT) or both, involving a higher&#xD;
      risk to develop type 2 diabetes mellitus (T2DM) in 10 years.&#xD;
&#xD;
      The efficacy of pharmacotherapy in the prevention of diabetes in adults with prediabetes has&#xD;
      been demonstrated, the first line of pharmacology treatment is metformin, on the other hand,&#xD;
      the traditional Chinese and Ayurverica medicine offer potential active substances for the&#xD;
      treatment of hyperglucemia like berberine.&#xD;
&#xD;
      Berberine is an extract with hypoglycemic effects in animal models as well as in clinical&#xD;
      trials in type 2 diabetes mellitus even compared to metformin, for this reason comparing it's&#xD;
      activity against metformin in prediabetes would provide impact information on a new&#xD;
      alternative treatment and compare with the standard pharmacological treatment.&#xD;
&#xD;
      The aim of the study evaluate the effect of administration of berberine versus metaformine on&#xD;
      glycemic control, insulin secretion and insulin sensitivity in patients with pre diabetes.&#xD;
&#xD;
      The investigators hypothesis is that the administration of berberine versus metformin&#xD;
      modifies glycemic control, insulin sensitivity and insulin secretion in patients with&#xD;
      prediabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A randomized, double-blind, placebo-controlled clinical trial in 28 patients with a diagnosis&#xD;
      of prediabetes (IFG and IGT) in accordance with the American Diabetes Association with out&#xD;
      treatment.&#xD;
&#xD;
      They will be assigned randomly two groups of 14 patients, one of the groups will receive 850&#xD;
      mg of metformin twice at day (before breakfast and before dinner) and one pill of placebo&#xD;
      (before lunch) for 14 weeks. There will be a running period, starting with a dose of 500 mg&#xD;
      the first week, the second week increasing to 1000 mg and from the third to the fourteenth&#xD;
      week will be a dose of 1500 mg.&#xD;
&#xD;
      The other group will receive 500 mg of berberine three times at day (each one before the&#xD;
      mealtime) for14 weeks. There will be a running period, starting with a dose of 850 mg the&#xD;
      first week, the second week dose of 850 mg of metformin plus one placebo pill and from the&#xD;
      third week to the fourteenth week will be a dose of 1700 mg ( two 850 mg metformin pills)&#xD;
      plus one placebo pill.&#xD;
&#xD;
      They will be measured fasting blood glucose, postprandial glucose levels and glycosylated&#xD;
      hemoglobin, and will be calculated Area Under Curve of glucose and insulin, total insulin&#xD;
      secretion (Insolinogenic index), first-phase of insulin secretion (Strumvoll index) and&#xD;
      insulin sensitivity (Matsuda index).&#xD;
&#xD;
      This protocol it's already approved by the local ethics committee and written informed&#xD;
      consent it's going to be obtained from all volunteers.&#xD;
&#xD;
      Statistical analysis will be presented through measures of central tendency and dispersion,&#xD;
      average and deviation standard for quantitative variables; frequencies and percentage for&#xD;
      qualitative variable. Qualitative variables will be analyzed by X2, will be used for&#xD;
      differences inter-group Mann-Whitney U Test and Wilcoxon Test for the within-groups&#xD;
      differences. It will be considered statistical significance p≤0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>March 2016</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Actual">February 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Fasting glucose levels</measure>
    <time_frame>Baseline to week 14</time_frame>
    <description>The fasting glucose levels will be evaluated at baseline and week 14 with enzymatic/ colorimetric techniques and the entered values reflect the fasting glucose level at week 14</description>
  </primary_outcome>
  <primary_outcome>
    <measure>postprandial glucose levels</measure>
    <time_frame>baseline to week 14</time_frame>
    <description>Postprandial glucose will be evaluated at baseline week 14 after a oral glucose tolerance test with enzymatic/ colorimetric techniques and the entered values reflect the insulin sensitivity at week 14</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Glycosylated hemoglobin</measure>
    <time_frame>baseline to week 14</time_frame>
    <description>Glycosylated hemoglobin will be evaluated at baseline and week 14 by Elisa and the entered values reflect the glycosylated hemoglobin at week 14</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total insulin secretion</measure>
    <time_frame>baseline to week 14</time_frame>
    <description>Total insulin secretion will be calculated at baseline and week 14 with insulinogenic index and the entered values reflect the total insulin secretion at week 14</description>
  </primary_outcome>
  <primary_outcome>
    <measure>First phase of insulin secretion</measure>
    <time_frame>baseline to week 14</time_frame>
    <description>The first phase of insulin secretion will be calculated at baseline and week 14 with Strumvoll index and the entered values reflect the first phase of insulin secretion at week 14</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Insulin sensitivity</measure>
    <time_frame>baseline to week 14</time_frame>
    <description>Insulin sensitivity will be calculated at baseline and week 14 with Matsuda index and the entered values reflect the insulin sensitivity at week 14</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Body Weight</measure>
    <time_frame>Baseline to week 14</time_frame>
    <description>The body weight will be measured at baseline, week 3, week 6, week 10, and week 14 with a bioimpedance balance and the entered values reflect the body weight at week 14</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body Mass Index</measure>
    <time_frame>Baseline to week 14</time_frame>
    <description>Body Mas Index will be calculated at baseline, week 3, week 6, week 10, and week 14 with the Quetelet index formula and the entered values reflect the body mass index at week 14</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body fat percentage</measure>
    <time_frame>Baseline to week 14</time_frame>
    <description>Body fat percentage will be evaluated at baseline, week 3, week 6, week 10, and week 14 by Bioimpedance technique and the entered values reflect the body fat percentage at week 14</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Waist circumference</measure>
    <time_frame>Baseline to week 14</time_frame>
    <description>Waist circumference will be evaluated at baseline, week 3, week 6, week 10 and week 14 by World Health Organization technique and the entered values reflect the waist circumference mesure at week 14</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>Baseline to week 14</time_frame>
    <description>Blood pressure will be measured at baseline,week 3, week 6, week 10 and week week 14 with a digital sphygmomanometer and the entered values reflect the blood pressure at week 14</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total cholesterol</measure>
    <time_frame>Baseline to week 14</time_frame>
    <description>Total cholesterol levels will be evaluated at baseline and week 14 by enzymatic/colorimetric techniques and the entered values reflect the total cholesterol level at week 14</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Triglycerides levels</measure>
    <time_frame>Baseline to week 14</time_frame>
    <description>Triglycerides levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques and the entered values reflect the triglycerides level at week 14</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>High density lipoprotein (c-HDL) levels</measure>
    <time_frame>Baseline to week 14</time_frame>
    <description>c-HDL levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 14</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Low density lipoprotein (c-LDL) levels</measure>
    <time_frame>Baseline to week 14</time_frame>
    <description>c-LDL levels will be will be calculated at baseline and week 14 with Friedewald Formula and the entered values reflect the c-HDL level at week 14</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alanine aminotransferase (ALT) levels</measure>
    <time_frame>Baseline to week 14</time_frame>
    <description>ALT levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aspartate aminotransferase (AST) levels</measure>
    <time_frame>Baseline to week 14</time_frame>
    <description>AST levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Creatinine levels</measure>
    <time_frame>Baseline to week 14</time_frame>
    <description>Creatinine levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">28</enrollment>
  <condition>Prediabetes</condition>
  <condition>Impaired Fasting Glucose</condition>
  <condition>Impaired Glucose Tolerance</condition>
  <arm_group>
    <arm_group_label>Berberine hydrochloride</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Berberine capsules, 500 mg, three per day before each meal during 12 weeks.&#xD;
The patients will have a forced titration period:&#xD;
First week they will receive one 500 mg capsule before breakfast Second week they will receive two 500 mg capsules (before breakfast and meal) From the third week until the end of the study, they will be receive three 500 mg capsules (before each meal)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Metformin capsules, 850 mg, two per day before breakfast and dinner and one placebo capsule before lunch during 12 weeks.&#xD;
The patients will have a forced titration period:&#xD;
First week they will receive one 850 mg capsule before breakfast Second week they will receive one 500 mg capsules (before breakfast) and one placebo capsule (before meal).&#xD;
From the third week until the end of the study, they will be receive two 850 mg capsules (before breakfast and dinner) and one placebo capsule (before meal).</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Berberine</intervention_name>
    <description>Berberine capsules, 500 mg, three per day before each meal during 14 weeks.&#xD;
The patients will have a running period during two weeks:&#xD;
First week they will receive one 500 mg capsule before breakfast Second week they will receive two 500 mg capsules (before breakfast and meal) From the third week until the end of the study (14 week), they will be receive three 500 mg</description>
    <arm_group_label>Berberine hydrochloride</arm_group_label>
    <other_name>Berberine hydrochloride</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Metformin capsules, 850 mg, two per day before breakfast and dinner and one placebo capsule before lunch during 14 weeks.&#xD;
The patients will have a running period:&#xD;
First week they will receive one 850 mg capsule before breakfast Second week they will receive one 500 mg capsules (before breakfast) and one placebo capsule (before meal).&#xD;
From the third week until the end of the study (14 week), they will be receive two 850 mg capsules (before breakfast and dinner) and one placebo capsule (before meal).</description>
    <arm_group_label>Metformin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients both sexes&#xD;
&#xD;
          -  Age between 31 and 60 years&#xD;
&#xD;
          -  Diagnosis of prediabetes according 2 ADA criteria (fasting blood glucose levels&#xD;
             between 100-125 mg/dl and postprandial blood glucose levels after an oral glucose&#xD;
             tolerance test with 75 of oral glucose between 140-199 mg/dl)&#xD;
&#xD;
          -  Body Mass Index from 25 to 34.9kg/m2&#xD;
&#xD;
          -  Informed consent signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women with confirmed or suspected pregnancy&#xD;
&#xD;
          -  Women under lactation and/or puerperium&#xD;
&#xD;
          -  Hypersensibility to ingredients of intervention&#xD;
&#xD;
          -  Physical impossibility for taking pills&#xD;
&#xD;
          -  Known uncontrolled renal, hepatic, heart or thyroid diseased&#xD;
&#xD;
          -  Diabetes diagnosis&#xD;
&#xD;
          -  Previous treatment for glucose&#xD;
&#xD;
          -  Body Mass Index ≥35 kg/m2&#xD;
&#xD;
          -  Glycosylated hemoglobin &gt; 6.5%&#xD;
&#xD;
          -  Triglycerides ≥500 mg/dL&#xD;
&#xD;
          -  Total cholesterol ≥240 mg/dL&#xD;
&#xD;
          -  Low density lipoprotein (c-LDL) ≥190 mg/dL&#xD;
&#xD;
          -  Blood Pressure ≥140/90 mmHg&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>31 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>KARINA GRISELDA PEREZ, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Guadalajara</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Instituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara</name>
      <address>
        <city>Guadalajara</city>
        <state>Jalisco</state>
        <zip>44340</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <last_update_submitted>May 22, 2023</last_update_submitted>
  <last_update_submitted_qc>May 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Guadalajara</investigator_affiliation>
    <investigator_full_name>Karina Griselda Pérez Rubio</investigator_full_name>
    <investigator_title>PhD</investigator_title>
  </responsible_party>
  <keyword>Prediabetes</keyword>
  <keyword>hyperglycemia</keyword>
  <keyword>Impaired Fasting Glucose</keyword>
  <keyword>Metformin</keyword>
  <keyword>Berberine</keyword>
  <keyword>glucose intolerance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Prediabetic State</mesh_term>
    <mesh_term>Glucose Intolerance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03029390
org study id: BM-Prediabetes
nct id: NCT03029390
lead sponsor: 
has dmc: No
Pre diabetes (PD) is a term that refers to alterations in glucose homeostasis, including
      impaired fasting glucose (IFG), Imparied glucose tolerance (IGT) or both, involving a higher
      risk to develop type 2 diabetes mellitus (T2DM) in 10 years.

      The efficacy of pharmacotherapy in the prevention of diabetes in adults with prediabetes has
      been demonstrated, the first line of pharmacology treatment is metformin, on the other hand,
      the traditional Chinese and Ayurverica medicine offer potential active substances for the
      treatment of hyperglucemia like berberine.

      Berberine is an extract with hypoglycemic effects in animal models as well as in clinical
      trials in type 2 diabetes mellitus even compared to metformin, for this reason comparing it's
      activity against metformin in prediabetes would provide impact information on a new
      alternative treatment and compare with the standard pharmacological treatment.

      The aim of the study evaluate the effect of administration of berberine versus metaformine on
      glycemic control, insulin secretion and insulin sensitivity in patients with pre diabetes.

      The investigators hypothesis is that the administration of berberine versus metformin
      modifies glycemic control, insulin sensitivity and insulin secretion in patients with
      prediabetes.
A randomized, double-blind, placebo-controlled clinical trial in 28 patients with a diagnosis
      of prediabetes (IFG and IGT) in accordance with the American Diabetes Association with out
      treatment.

      They will be assigned randomly two groups of 14 patients, one of the groups will receive 850
      mg of metformin twice at day (before breakfast and before dinner) and one pill of placebo
      (before lunch) for 14 weeks. There will be a running period, starting with a dose of 500 mg
      the first week, the second week increasing to 1000 mg and from the third to the fourteenth
      week will be a dose of 1500 mg.

      The other group will receive 500 mg of berberine three times at day (each one before the
      mealtime) for14 weeks. There will be a running period, starting with a dose of 850 mg the
      first week, the second week dose of 850 mg of metformin plus one placebo pill and from the
      third week to the fourteenth week will be a dose of 1700 mg ( two 850 mg metformin pills)
      plus one placebo pill.

      They will be measured fasting blood glucose, postprandial glucose levels and glycosylated
      hemoglobin, and will be calculated Area Under Curve of glucose and insulin, total insulin
      secretion (Insolinogenic index), first-phase of insulin secretion (Strumvoll index) and
      insulin sensitivity (Matsuda index).

      This protocol it's already approved by the local ethics committee and written informed
      consent it's going to be obtained from all volunteers.

      Statistical analysis will be presented through measures of central tendency and dispersion,
      average and deviation standard for quantitative variables; frequencies and percentage for
      qualitative variable. Qualitative variables will be analyzed by X2, will be used for
      differences inter-group Mann-Whitney U Test and Wilcoxon Test for the within-groups
      differences. It will be considered statistical significance p≤0.05.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Fasting glucose levels
time frame: Baseline to week 14
description: The fasting glucose levels will be evaluated at baseline and week 14 with enzymatic/ colorimetric techniques and the entered values reflect the fasting glucose level at week 14
measure: postprandial glucose levels
time frame: baseline to week 14
description: Postprandial glucose will be evaluated at baseline week 14 after a oral glucose tolerance test with enzymatic/ colorimetric techniques and the entered values reflect the insulin sensitivity at week 14
measure: Glycosylated hemoglobin
time frame: baseline to week 14
description: Glycosylated hemoglobin will be evaluated at baseline and week 14 by Elisa and the entered values reflect the glycosylated hemoglobin at week 14
measure: Total insulin secretion
time frame: baseline to week 14
description: Total insulin secretion will be calculated at baseline and week 14 with insulinogenic index and the entered values reflect the total insulin secretion at week 14
measure: First phase of insulin secretion
time frame: baseline to week 14
description: The first phase of insulin secretion will be calculated at baseline and week 14 with Strumvoll index and the entered values reflect the first phase of insulin secretion at week 14
measure: Insulin sensitivity
time frame: baseline to week 14
description: Insulin sensitivity will be calculated at baseline and week 14 with Matsuda index and the entered values reflect the insulin sensitivity at week 14
measure: Body Weight
time frame: Baseline to week 14
description: The body weight will be measured at baseline, week 3, week 6, week 10, and week 14 with a bioimpedance balance and the entered values reflect the body weight at week 14
measure: Body Mass Index
time frame: Baseline to week 14
description: Body Mas Index will be calculated at baseline, week 3, week 6, week 10, and week 14 with the Quetelet index formula and the entered values reflect the body mass index at week 14
measure: Body fat percentage
time frame: Baseline to week 14
description: Body fat percentage will be evaluated at baseline, week 3, week 6, week 10, and week 14 by Bioimpedance technique and the entered values reflect the body fat percentage at week 14
measure: Waist circumference
time frame: Baseline to week 14
description: Waist circumference will be evaluated at baseline, week 3, week 6, week 10 and week 14 by World Health Organization technique and the entered values reflect the waist circumference mesure at week 14
measure: Blood pressure
time frame: Baseline to week 14
description: Blood pressure will be measured at baseline,week 3, week 6, week 10 and week week 14 with a digital sphygmomanometer and the entered values reflect the blood pressure at week 14
measure: Total cholesterol
time frame: Baseline to week 14
description: Total cholesterol levels will be evaluated at baseline and week 14 by enzymatic/colorimetric techniques and the entered values reflect the total cholesterol level at week 14
measure: Triglycerides levels
time frame: Baseline to week 14
description: Triglycerides levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques and the entered values reflect the triglycerides level at week 14
measure: High density lipoprotein (c-HDL) levels
time frame: Baseline to week 14
description: c-HDL levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 14
measure: Low density lipoprotein (c-LDL) levels
time frame: Baseline to week 14
description: c-LDL levels will be will be calculated at baseline and week 14 with Friedewald Formula and the entered values reflect the c-HDL level at week 14
measure: Alanine aminotransferase (ALT) levels
time frame: Baseline to week 14
description: ALT levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques
measure: Aspartate aminotransferase (AST) levels
time frame: Baseline to week 14
description: AST levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques
measure: Creatinine levels
time frame: Baseline to week 14
description: Creatinine levels will be evaluated at baseline and week 14 with enzymatic/colorimetric techniques
arm group label: Berberine hydrochloride
arm group type: Experimental
description: Berberine capsules, 500 mg, three per day before each meal during 12 weeks.
The patients will have a forced titration period:
First week they will receive one 500 mg capsule before breakfast Second week they will receive two 500 mg capsules (before breakfast and meal) From the third week until the end of the study, they will be receive three 500 mg capsules (before each meal)
arm group label: Metformin
arm group type: Experimental
description: Metformin capsules, 850 mg, two per day before breakfast and dinner and one placebo capsule before lunch during 12 weeks.
The patients will have a forced titration period:
First week they will receive one 850 mg capsule before breakfast Second week they will receive one 500 mg capsules (before breakfast) and one placebo capsule (before meal).
From the third week until the end of the study, they will be receive two 850 mg capsules (before breakfast and dinner) and one placebo capsule (before meal).
intervention type: Dietary Supplement
intervention name: Berberine
description: Berberine capsules, 500 mg, three per day before each meal during 14 weeks.
The patients will have a running period during two weeks:
First week they will receive one 500 mg capsule before breakfast Second week they will receive two 500 mg capsules (before breakfast and meal) From the third week until the end of the study (14 week), they will be receive three 500 mg
arm group label: Berberine hydrochloride
other name: Berberine hydrochloride
intervention type: Drug
intervention name: Metformin
description: Metformin capsules, 850 mg, two per day before breakfast and dinner and one placebo capsule before lunch during 14 weeks.
The patients will have a running period:
First week they will receive one 850 mg capsule before breakfast Second week they will receive one 500 mg capsules (before breakfast) and one placebo capsule (before meal).
From the third week until the end of the study (14 week), they will be receive two 850 mg capsules (before breakfast and dinner) and one placebo capsule (before meal).
arm group label: Metformin
criteria: 
gender: All
minimum age: 31 Years
maximum age: 60 Years
healthy volunteers: No
last name: KARINA GRISELDA PEREZ, PhD
role: Principal Investigator
affiliation: University of Guadalajara
facility: 
country: Mexico
responsible party type: Principal Investigator
investigator affiliation: University of Guadalajara
investigator full name: Karina Griselda Pérez Rubio
investigator title: PhD
mesh term: Insulin Resistance
mesh term: Prediabetic State
mesh term: Glucose Intolerance
mesh term: Metformin