This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Continuous Glucose Monitoring Evaluation of Exenatide Twice Daily Versus Insulin Glargine

This study has been completed.
Sponsor:
Collaborators:
International Diabetes Center at Park Nicollet
Sanofi
Information provided by (Responsible Party):
HealthPartners Institute
ClinicalTrials.gov Identifier:
NCT01089569
First received: March 17, 2010
Last updated: April 19, 2017
Last verified: October 2013
  Purpose
The primary purpose of this study is to compare the effect on 24-hour blood glucose patterns, HbA1c, and weight management when adding insulin glargine, or exenatide, or a combination of insulin glargine and exenatide to metformin.

Condition Intervention
Type 2 Diabetes Drug: Exenatide Drug: Insulin Glargine

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Masking Description:
Subjects were randomized and then told the medications they were randomized to. Since the medications were already on the market, there was no need for masking for any involved individuals.
Primary Purpose: Treatment
Official Title: Evaluation of Insulin Glargine and Exenatide: A Randomized Clinical Trial With Continuous Glucose Monitoring and Ambulatory Glucose Profile Analysis

Resource links provided by NLM:


Further study details as provided by HealthPartners Institute:

Primary Outcome Measures:
  • HbA1c Change [ Time Frame: baseline to final visit (32 weeks) ]

    Measure the changes in HbA1C attributable to exenatide, insulin glargine and their combination.

    Employ CGM with AGP analysis to determine if there is an incremental benefit for subjects who do not reach target to add exenatide to insulin glargine or insulin glargine to exenatide in patients taking metformin.



Secondary Outcome Measures:
  • Change From Baseline in Incidence of Hypoglycemia (Frequency) [ Time Frame: baseline to final visit (32 weeks) ]

    Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes.

    Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves- iv. Incidence of hypoglycemia (frequency)

    Change from baseline was calculated as mean incidence rate at baseline minus mean incidence rate at final visit (32 weeks)


  • Change From Baseline in Incidence of Hypoglycemia (Degree) [ Time Frame: baseline to final visit (32 weeks) ]

    Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes.

    Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves- iv. Incidence of hypoglycemia (degree) Change from baseline was calculated as mean incidence percentage at baseline minus mean incidence percentage at final visit (32 weeks)


  • Change From Baseline in Glucose Stability (Absolute Hourly Rate of Change in Median Curve) [ Time Frame: baseline to final visit (32 weeks) ]

    Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes.

    Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves iii. Glucose stability (absolute hourly rate of change in median curve)

    Change from baseline was calculated as mean absolute hourly rate of change in median curve at baseline minus rate at final visit (32 weeks). Mean absolute hourly rate of change in the smoothed median curve is calculated as delta subscript MC = (|p subscript 50 zero - p subscript 50 23|+Sum superscript 23 subscript i = 1| p subscript 50i - p subscript 50 i-1| over T.

    i = hour of day p subscript 50i = smoothed 50th percentile value for ith hour of day T = total # of non-missing hourly smoothed percentiles


  • Change From Baseline in CGM Glucose Variability [ Time Frame: baseline to final visit (32 weeks) ]

    Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes.

    Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves- ii. Glucose variability (inter-quartile range)

    IQR is the difference between the 75th and 25th percentiles. Change from baseline was calculated as IQR at baseline minus IQR value at final visit (32 weeks).


  • Change From Baseline in Glucose Exposure (Area Under the Diurnal Median Curve or AUC) [ Time Frame: baseline - final visit (32 weeks) ]

    Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes.

    Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves- i. Glucose exposure (area under the diurnal median curve) Change from baseline was calculated as area under the diurnal median curve at baseline minus AUC value at final visit (32 weeks).

    AUC is calculated using modified rectangle method AUC = sum of superscript 23, subscript i=0 P subscript 50i I = hour of day P subscript 50i = smoother 50th percentile value for ith hour of day


  • Change From Baseline in Weight Changes [ Time Frame: baseline - final visit (32 weeks) ]

    Measure the changes in weight attributable to exenatide, insulin glargine and their combinations.

    Employ CGM with AGP analysis to determine if there is an incremental benefit for subjects who do not reach target to add exenatide to insulin glargine or insulin glargine to exenatide in patients taking metformin.

    Change from baseline was calculated as weight in pounds at baseline minus weight in pounds at final visit (32 weeks).



Enrollment: 60
Study Start Date: April 2010
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Exenatide
5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study
Drug: Exenatide
5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study
Other Name: Bydureon
Active Comparator: Insulin Glargine
.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Drug: Insulin Glargine
.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Other Name: Lantus
Active Comparator: Exenatide + Insulin Glargine

Exenatide: 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study

+ Insulin Glargine: 0.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results

Drug: Exenatide
5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study
Other Name: Bydureon
Drug: Insulin Glargine
.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Other Name: Lantus

Detailed Description:

The primary objective of this study was to characterize the diurnal glucose patterns produced by insulin glargine alone, exenatide (GLP-1 agonist) alone and the combination of insulin glargine and exenatide in subjects taking stable dose of metformin and to evaluate their efficacy in terms of improvement in glucose exposure, variability, stability, incidence of hypoglycemia and weight management.

An ancillary study was approved as part of this study. The purpose of the ancillary study was to use CGM to characterize the glycemic response to a fixed breakfast meal consumed by study participants receiving different medications.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects ≥18 and ≤75 years of age
  • Clinical diagnosis of type 2 diabetes
  • Diabetes duration ≥ 1 year
  • HbA1c ≥7.0%
  • Currently treated with metformin (HbA1c ≤9%) or metformin/sulfonylurea (SU) (HbA1c ≤8%)or SU alone (HbA1c ≤8%)

Exclusion Criteria:

  • Previously treated with insulin or incretin-based therapy
  • Treated with a thiazolidinedione within past 6 weeks
  • Taken oral or injected prednisone or cortisone medications in the previous 30 days
  • Any pancreatic disease or at high risk of pancreatitis (history of alcohol abuse, active gallbladder disease)
  • Serum creatinine >1.4mg/dL (women) or >1.5 mg/dL (men)
  • eGFR (Estimated Glomerular Filtration Rate) <30 ml/min (using MDRD/ Modification of Diet in Renal Disease equation)
  • ALT(Alanine Transaminase) > 2x Upper Limit of Normal (ULN)
  • Presence of any severe medical or psychological condition or chronic conditions/infections that in the opinion of the Investigator would compromise he subject's safety or successful participation in the study
  • Currently pregnant or planning pregnancy during the study period
  • Unable to follow the study protocol
  • Unable to speak, read and write in English
  • Uncontrolled hyperglycemia with HbA1c > 9% on metformin or >8% on SU or metformin/SU combination or ketonuria requiring immediate insulin therapy
  • At the investigator's discretion for other medical or psychological reasons
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01089569

Locations
United States, Minnesota
International Diabetes Center
Minneapolis, Minnesota, United States, 55416
Sponsors and Collaborators
HealthPartners Institute
International Diabetes Center at Park Nicollet
Sanofi
Investigators
Principal Investigator: Richard M Bergenstal, MD International Diabetes Center at Park Nicollet
Principal Investigator: Roger S Mazze, PhD International Diabetes Center at Park Nicollet
Principal Investigator: Elinor S Strock, APRN International Diabetes Center at Park Nicollet
  More Information

Publications:
Responsible Party: HealthPartners Institute
ClinicalTrials.gov Identifier: NCT01089569     History of Changes
Other Study ID Numbers: 03951-10-C
Study First Received: March 17, 2010
Results First Received: October 28, 2016
Last Updated: April 19, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by HealthPartners Institute:
diabetes
continuous glucose monitoring
exenatide
insulin glargine

Additional relevant MeSH terms:
Insulin, Globin Zinc
Exenatide
Insulin
Insulin Glargine
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on June 26, 2017