<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/NCT03004612</url>
  </required_header>
  <id_info>
    <org_study_id>CEI-22-16</org_study_id>
    <nct_id>NCT03004612</nct_id>
  </id_info>
  <brief_title>Effect of Linagliptin + Metformin vs Metformin Alone in Patients With Prediabetes</brief_title>
  <acronym>PRELLIM</acronym>
  <official_title>Effect of Linagliptin + Metformin vs Metformin Alone on the Role of Pancreatic Islet Function, Insulin Resistance and Markers of Cardiovascular Risk in Patients With Prediabetes: Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidad de Guanajuato</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hospital Regional de Alta Especialidad del Bajio</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universidad de Guanajuato</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Type 2 diabetes is a worldwide epidemic disease, and preventive strategies are needed to face&#xD;
      this health problem. The goal of this clinical trial is to evaluate the effect of linagliptin&#xD;
      + metformin vs metformin alone on physiopathological parameters, such as glucose metabolism,&#xD;
      insulin resistance, insulin secretion and pancreatic beta cell function in patients with&#xD;
      impaired fasting glucose plus impaired glucose tolerance, during 24 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The main goal of this clinical trial is to compare the effect of two different treatments&#xD;
      during 24 months:&#xD;
&#xD;
        1. Lifestyle modification program + metformin 850mg twice daily&#xD;
&#xD;
        2. Lifestyle modification program + linagliptin (2.5mg) and metformin (850mg) twice daily&#xD;
&#xD;
      on the following parameters, after 24 months of treatment:&#xD;
&#xD;
        1. Glucose metabolism, evaluated by the oral glucose tolerance&#xD;
&#xD;
        2. Insulin resistance, evaluated by the oral glucose tolerance in 100% of the patients and&#xD;
           by hyperglycemic clamp in 10 % of the patients&#xD;
&#xD;
        3. Insulin secretion, evaluated by the oral glucose tolerance in 100% of the patients and&#xD;
           by hyperglycemic clamp in 10 % of the patients&#xD;
&#xD;
        4. Pancreatic beta cell function, evaluated by the oral glucose tolerance in 100% of the&#xD;
           patients and by hyperglycemic clamp in 10 % of the patients&#xD;
&#xD;
        5. Systemic inflammation and cardiovascular risk factors, evaluated by cytokines&#xD;
           interlelukin-6 (IL6), C-reactive protein (PCR), and measurement of the intima media&#xD;
           thickness by ultrasound.&#xD;
&#xD;
      All the patients will have a basal evaluation with an oral glucose tolerance test, lipid&#xD;
      profile, body composition, and IMT measurement by ultrasonography; and 10 % will be invited&#xD;
      for the hyperglycemic clamp. After the basal evaluation, if the patients result with IMPAIRED&#xD;
      GLUCOSE TOLERANCE and have at least 2 risk factors, they will be invited to the intervention&#xD;
      phase where they will be randomized to one of the two treatment groups.&#xD;
&#xD;
      Patients will have a follow-up visit every month to review the adherence to the lifestyle&#xD;
      modification program and to the medication. Every 6 months OGTT will be performed on all the&#xD;
      patients, and in a subset of patients hyperglycemic clamp will be performed at 0, 6 and 12&#xD;
      months. After 18 and 24 months, patients will repeat the same evaluation performed as the&#xD;
      basal evaluation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2016</start_date>
  <completion_date type="Actual">June 2019</completion_date>
  <primary_completion_date type="Actual">May 2019</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from basal fasting and post2h OGTT glucose levels at 12 and 24 months</measure>
    <time_frame>12 and 24 months</time_frame>
    <description>Fasting and post-2h OGTT glucose values (mg/dl)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from basal pancreatic beta cell function at 12 and 24 months</measure>
    <time_frame>12 and 24 months</time_frame>
    <description>Evaluated with the measurements of glucose and insulin during the oral glucose tolerance test; as well as with the glucose and insulin measurements from the hyperglycemic clamp, as the Disposition index.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from basal insulin sensitivity at 12 and 24 months</measure>
    <time_frame>12 and 24 months</time_frame>
    <description>Insulin sensitivity evaluated during the oral glucose tolerance test by the Matsuda index, and reported as an arbitrary units.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from basal Weight at 12 and 24 months</measure>
    <time_frame>12 and 24 months</time_frame>
    <description>Weight measurement during the study, in kg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of type 2 diabetes</measure>
    <time_frame>24 months</time_frame>
    <description>New reported cases with T2D according the the ADA diagnostic criteria</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">144</enrollment>
  <condition>Prediabetic State</condition>
  <condition>Insulin Resistance</condition>
  <arm_group>
    <arm_group_label>Linagliptin + Metformin plus lifestyle</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients are randomized to receive for 24 months Linagliptin 2.5mg + metformin 850mg every 12 hours. The start of the dose in this group will be gradual so that at the month of treatment the patient can be with the full doses. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90-150min/week.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metformin plus lifestyle</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients are randomized to receive for 24 months Metformin 850mg every 12 hours. The start of the dose in this group will be gradual so that at the month of treatment the patient can be with the full doses. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90-150min/week.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Linagliptin + metformin</intervention_name>
    <description>Linagliptin-Metformin 2.5/850mg twice daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling</description>
    <arm_group_label>Linagliptin + Metformin plus lifestyle</arm_group_label>
    <other_name>Tradjenta Duo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Metformin 850mg twice daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling</description>
    <arm_group_label>Metformin plus lifestyle</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with prediabetes, defined for the existence impaired glucose tolerance&#xD;
             (Glucose between 140 and 199 mg/dL at the 2 hours of the Oral Glucose Tolerance test&#xD;
             (OGTT) ) with or without impaired fasting glucose (Fasting glucose between 100 and 125&#xD;
             mg/dL)&#xD;
&#xD;
          -  Patients who accept to participate in the study and sign the informed consent letter.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with diagnosed Type 2 Diabetes Mellitus previously or detected during the&#xD;
             OGTT&#xD;
&#xD;
          -  Patients in actual treatment or during the last 3 months with metformin, pioglitazone&#xD;
             or another antidiabetic drug, including insulin.&#xD;
&#xD;
          -  Serum creatinine &gt; 1.6 mg/dL&#xD;
&#xD;
          -  Hypertriglyceridemia very high (&gt;500 mg/dL)&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Altered arterial hypertension (Systolic &gt; 180 mmHg or Diastolic &gt;105 mmHg)&#xD;
&#xD;
          -  Excessive alcohol intake, acute or chronic&#xD;
&#xD;
          -  Medications or medical conditions that affect glucose homeostasis (thiazides, beta&#xD;
             blockers, glucocorticoids for systemic use, weight-reducing drugs or anorexigenics,&#xD;
             Cushing's syndrome, Thyrotoxicosis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rodolfo Guardado-Mendoza, MDPhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universidad de Guanajuato</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universidad de Guanajuato</name>
      <address>
        <city>León</city>
        <state>Guanajuato</state>
        <zip>37670</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <reference>
    <citation>King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998 Sep;21(9):1414-31. doi: 10.2337/diacare.21.9.1414.</citation>
    <PMID>9727886</PMID>
  </reference>
  <reference>
    <citation>Faerch K, Borch-Johnsen K, Holst JJ, Vaag A. Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes? Diabetologia. 2009 Sep;52(9):1714-23. doi: 10.1007/s00125-009-1443-3. Epub 2009 Jul 10.</citation>
    <PMID>19590846</PMID>
  </reference>
  <reference>
    <citation>Faerch K, Vaag A, Holst JJ, Glumer C, Pedersen O, Borch-Johnsen K. Impaired fasting glycaemia vs impaired glucose tolerance: similar impairment of pancreatic alpha and beta cell function but differential roles of incretin hormones and insulin action. Diabetologia. 2008 May;51(5):853-61. doi: 10.1007/s00125-008-0951-x. Epub 2008 Mar 4.</citation>
    <PMID>18317726</PMID>
  </reference>
  <reference>
    <citation>Faerch K, Vaag A, Holst JJ, Hansen T, Jorgensen T, Borch-Johnsen K. Natural history of insulin sensitivity and insulin secretion in the progression from normal glucose tolerance to impaired fasting glycemia and impaired glucose tolerance: the Inter99 study. Diabetes Care. 2009 Mar;32(3):439-44. doi: 10.2337/dc08-1195. Epub 2008 Dec 3.</citation>
    <PMID>19056613</PMID>
  </reference>
  <reference>
    <citation>Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, Liu PA, Jiang XG, Jiang YY, Wang JP, Zheng H, Zhang H, Bennett PH, Howard BV. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. 1997 Apr;20(4):537-44. doi: 10.2337/diacare.20.4.537.</citation>
    <PMID>9096977</PMID>
  </reference>
  <reference>
    <citation>Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3;344(18):1343-50. doi: 10.1056/NEJM200105033441801.</citation>
    <PMID>11333990</PMID>
  </reference>
  <reference>
    <citation>Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.</citation>
    <PMID>11832527</PMID>
  </reference>
  <reference>
    <citation>Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M; STOP-NIDDM Trail Research Group. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet. 2002 Jun 15;359(9323):2072-7. doi: 10.1016/S0140-6736(02)08905-5.</citation>
    <PMID>12086760</PMID>
  </reference>
  <reference>
    <citation>Drucker DJ, Sherman SI, Gorelick FS, Bergenstal RM, Sherwin RS, Buse JB. Incretin-based therapies for the treatment of type 2 diabetes: evaluation of the risks and benefits. Diabetes Care. 2010 Feb;33(2):428-33. doi: 10.2337/dc09-1499. No abstract available.</citation>
    <PMID>20103558</PMID>
  </reference>
  <reference>
    <citation>Rosenstock J, Klaff LJ, Schwartz S, Northrup J, Holcombe JH, Wilhelm K, Trautmann M. Effects of exenatide and lifestyle modification on body weight and glucose tolerance in obese subjects with and without pre-diabetes. Diabetes Care. 2010 Jun;33(6):1173-5. doi: 10.2337/dc09-1203. Epub 2010 Mar 23.</citation>
    <PMID>20332357</PMID>
  </reference>
  <reference>
    <citation>Kim SH, Liu A, Ariel D, Abbasi F, Lamendola C, Grove K, Tomasso V, Reaven G. Pancreatic beta cell function following liraglutide-augmented weight loss in individuals with prediabetes: analysis of a randomised, placebo-controlled study. Diabetologia. 2014 Mar;57(3):455-62. doi: 10.1007/s00125-013-3134-3. Epub 2013 Dec 11.</citation>
    <PMID>24326527</PMID>
  </reference>
  <reference>
    <citation>Heise T, Graefe-Mody EU, Huttner S, Ring A, Trommeshauser D, Dugi KA. Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients. Diabetes Obes Metab. 2009 Aug;11(8):786-94. doi: 10.1111/j.1463-1326.2009.01046.x. Epub 2009 May 19.</citation>
    <PMID>19476474</PMID>
  </reference>
  <reference>
    <citation>Craddy P, Palin HJ, Johnson KI. Comparative effectiveness of dipeptidylpeptidase-4 inhibitors in type 2 diabetes: a systematic review and mixed treatment comparison. Diabetes Ther. 2014 Jun;5(1):1-41. doi: 10.1007/s13300-014-0061-3. Epub 2014 Mar 25.</citation>
    <PMID>24664619</PMID>
  </reference>
  <reference>
    <citation>Del Prato S, Taskinen MR, Owens DR, von Eynatten M, Emser A, Gong Y, Chiavetta S, Patel S, Woerle HJ. Efficacy and safety of linagliptin in subjects with type 2 diabetes mellitus and poor glycemic control: pooled analysis of data from three placebo-controlled phase III trials. J Diabetes Complications. 2013 May-Jun;27(3):274-9. doi: 10.1016/j.jdiacomp.2012.11.008. Epub 2013 Feb 9.</citation>
    <PMID>23403068</PMID>
  </reference>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>December 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>July 5, 2019</last_update_submitted>
  <last_update_submitted_qc>July 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidad de Guanajuato</investigator_affiliation>
    <investigator_full_name>Rodolfo Guardado Mendoza</investigator_full_name>
    <investigator_title>MDPhD</investigator_title>
  </responsible_party>
  <keyword>prediabetes</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>
    <mesh_term>Linagliptin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 30, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/12/NCT03004612/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03004612
org study id: CEI-22-16
nct id: NCT03004612
lead sponsor: 
collaborator: 
has dmc: Yes
Type 2 diabetes is a worldwide epidemic disease, and preventive strategies are needed to face
      this health problem. The goal of this clinical trial is to evaluate the effect 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 24 months.
The main goal of this clinical trial is to compare the effect of two different treatments
      during 24 months:

        1. Lifestyle modification program + metformin 850mg twice daily

        2. Lifestyle modification program + linagliptin (2.5mg) and metformin (850mg) twice daily

      on the following parameters, after 24 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 and
           by hyperglycemic clamp in 10 % of the patients

        3. Insulin secretion, evaluated by the oral glucose tolerance in 100% of the patients and
           by hyperglycemic clamp in 10 % of the patients

        4. Pancreatic beta cell function, evaluated by the oral glucose tolerance in 100% of the
           patients and by hyperglycemic clamp in 10 % of the patients

        5. Systemic inflammation and cardiovascular risk factors, evaluated by cytokines
           interlelukin-6 (IL6), C-reactive protein (PCR), and measurement of the intima media
           thickness by ultrasound.

      All the patients will have a basal evaluation with an oral glucose tolerance test, lipid
      profile, body composition, and IMT measurement by ultrasonography; and 10 % will be invited
      for the hyperglycemic clamp. After the basal evaluation, if the patients result with 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. Every 6 months OGTT will be performed on all the
      patients, and in a subset of patients hyperglycemic clamp will be performed at 0, 6 and 12
      months. After 18 and 24 months, patients will repeat the same evaluation performed as the
      basal evaluation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change from basal fasting and post2h OGTT glucose levels at 12 and 24 months
time frame: 12 and 24 months
description: Fasting and post-2h OGTT glucose values (mg/dl)
measure: Change from basal pancreatic beta cell function at 12 and 24 months
time frame: 12 and 24 months
description: Evaluated with the measurements of glucose and insulin during the oral glucose tolerance test; as well as with the glucose and insulin measurements from the hyperglycemic clamp, as the Disposition index.
measure: Change from basal insulin sensitivity at 12 and 24 months
time frame: 12 and 24 months
description: Insulin sensitivity evaluated during the oral glucose tolerance test by the Matsuda index, and reported as an arbitrary units.
measure: Change from basal Weight at 12 and 24 months
time frame: 12 and 24 months
description: Weight measurement during the study, in kg
measure: Incidence of type 2 diabetes
time frame: 24 months
description: New reported cases with T2D according the the ADA diagnostic criteria
arm group label: Linagliptin + Metformin plus lifestyle
arm group type: Experimental
description: Patients are randomized to receive for 24 months Linagliptin 2.5mg + metformin 850mg every 12 hours. The start of the dose in this group will be gradual so that at the month of treatment the patient can be with the full doses. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90-150min/week.
arm group label: Metformin plus lifestyle
arm group type: Active Comparator
description: Patients are randomized to receive for 24 months Metformin 850mg every 12 hours. The start of the dose in this group will be gradual so that at the month of treatment the patient can be with the full doses. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90-150min/week.
intervention type: Combination Product
intervention name: Linagliptin + metformin
description: Linagliptin-Metformin 2.5/850mg twice daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling
arm group label: Linagliptin + Metformin plus lifestyle
other name: Tradjenta Duo
intervention type: Drug
intervention name: Metformin
description: Metformin 850mg twice daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling
arm group label: Metformin plus lifestyle
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Rodolfo Guardado-Mendoza, MDPhD
role: Principal Investigator
affiliation: Universidad de Guanajuato
facility: 
country: Mexico
citation: King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998 Sep;21(9):1414-31. doi: 10.2337/diacare.21.9.1414.
PMID: 9727886
citation: Faerch K, Borch-Johnsen K, Holst JJ, Vaag A. Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes? Diabetologia. 2009 Sep;52(9):1714-23. doi: 10.1007/s00125-009-1443-3. Epub 2009 Jul 10.
PMID: 19590846
citation: Faerch K, Vaag A, Holst JJ, Glumer C, Pedersen O, Borch-Johnsen K. Impaired fasting glycaemia vs impaired glucose tolerance: similar impairment of pancreatic alpha and beta cell function but differential roles of incretin hormones and insulin action. Diabetologia. 2008 May;51(5):853-61. doi: 10.1007/s00125-008-0951-x. Epub 2008 Mar 4.
PMID: 18317726
citation: Faerch K, Vaag A, Holst JJ, Hansen T, Jorgensen T, Borch-Johnsen K. Natural history of insulin sensitivity and insulin secretion in the progression from normal glucose tolerance to impaired fasting glycemia and impaired glucose tolerance: the Inter99 study. Diabetes Care. 2009 Mar;32(3):439-44. doi: 10.2337/dc08-1195. Epub 2008 Dec 3.
PMID: 19056613
citation: Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, Liu PA, Jiang XG, Jiang YY, Wang JP, Zheng H, Zhang H, Bennett PH, Howard BV. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. 1997 Apr;20(4):537-44. doi: 10.2337/diacare.20.4.537.
PMID: 9096977
citation: Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3;344(18):1343-50. doi: 10.1056/NEJM200105033441801.
PMID: 11333990
citation: Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.
PMID: 11832527
citation: Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M; STOP-NIDDM Trail Research Group. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet. 2002 Jun 15;359(9323):2072-7. doi: 10.1016/S0140-6736(02)08905-5.
PMID: 12086760
citation: Drucker DJ, Sherman SI, Gorelick FS, Bergenstal RM, Sherwin RS, Buse JB. Incretin-based therapies for the treatment of type 2 diabetes: evaluation of the risks and benefits. Diabetes Care. 2010 Feb;33(2):428-33. doi: 10.2337/dc09-1499. No abstract available.
PMID: 20103558
citation: Rosenstock J, Klaff LJ, Schwartz S, Northrup J, Holcombe JH, Wilhelm K, Trautmann M. Effects of exenatide and lifestyle modification on body weight and glucose tolerance in obese subjects with and without pre-diabetes. Diabetes Care. 2010 Jun;33(6):1173-5. doi: 10.2337/dc09-1203. Epub 2010 Mar 23.
PMID: 20332357
citation: Kim SH, Liu A, Ariel D, Abbasi F, Lamendola C, Grove K, Tomasso V, Reaven G. Pancreatic beta cell function following liraglutide-augmented weight loss in individuals with prediabetes: analysis of a randomised, placebo-controlled study. Diabetologia. 2014 Mar;57(3):455-62. doi: 10.1007/s00125-013-3134-3. Epub 2013 Dec 11.
PMID: 24326527
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responsible party type: Principal Investigator
investigator affiliation: Universidad de Guanajuato
investigator full name: Rodolfo Guardado Mendoza
investigator title: MDPhD
mesh term: Insulin Resistance
mesh term: Prediabetic State
mesh term: Glucose Intolerance
mesh term: Metformin
mesh term: Linagliptin
sharing ipd: No
provided document: 