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| Name | Class |
|---|---|
| International Diabetes Center at Park Nicollet | OTHER |
| Sanofi | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Exenatide | Active Comparator | 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study |
|
| Insulin Glargine | Active Comparator | .1 unit per kg to start, titrated based on Continuous Glucose Monitoring results |
|
| Exenatide + Insulin Glargine | Active Comparator | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exenatide | Drug | 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study |
|
| Measure | Description | Time Frame |
|---|---|---|
| HbA1c Change | 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. | baseline to final visit (32 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Incidence of Hypoglycemia (Frequency) | 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| International Diabetes Center | Minneapolis | Minnesota | 55416 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18473688 | Background | Mazze RS, Strock E, Wesley D, Borgman S, Morgan B, Bergenstal R, Cuddihy R. Characterizing glucose exposure for individuals with normal glucose tolerance using continuous glucose monitoring and ambulatory glucose profile analysis. Diabetes Technol Ther. 2008 Jun;10(3):149-59. doi: 10.1089/dia.2007.0293. | |
| 19454385 | Background |
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| ID | Title | Description |
|---|---|---|
| FG000 | Exenatide | 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study |
| FG001 | Insulin Glargine | .1 unit per kg to start, titrated based on Continuous Glucose Monitoring results |
| FG002 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Exenatide | 5 mcg BID for 1 month increasing to 10 mcg BID for the remainder of the study Exenatide: refer to Arm detail |
| BG001 | Insulin Glargine | .1 unit per kg to start, titrated based on Continuous Glucose Monitoring results Insulin Glargine: refer to Arm detail |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | HbA1c Change | 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. | Posted | Mean | Standard Deviation | %HbA1c | baseline to final visit (32 weeks) |
|
Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Exenatide | 5 mcg BID for 1 month increasing to 10 mcg BID for the remainder of the study Exenatide: refer to Arm detail |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nausea and vomiting | Gastrointestinal disorders | Systematic Assessment | 17 subjects on Exenatide experienced nausea and vomiting. All resolved except for 1 subject were it persisted through the end of the study. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Richard M. Bergenstal | International Diabetes Center | 952-993-1913 | richard.bergenstal@parknicollet.com |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D000077270 | Exenatide |
| D000069036 | Insulin Glargine |
| ID | Term |
|---|---|
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014688 | Venoms |
| D045424 | Complex Mixtures |
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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.
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| Insulin Glargine | Drug | .1 unit per kg to start, titrated based on Continuous Glucose Monitoring results |
|
|
| baseline to final visit (32 weeks) |
| Change From Baseline in Incidence of Hypoglycemia (Degree) | 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) | baseline to final visit (32 weeks) |
| Change From Baseline in Glucose Stability (Absolute Hourly Rate of Change in Median Curve) | 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 | baseline to final visit (32 weeks) |
| Change From Baseline in CGM Glucose Variability | 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). | baseline to final visit (32 weeks) |
| Change From Baseline in Glucose Exposure (Area Under the Diurnal Median Curve or AUC) | 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 | baseline - final visit (32 weeks) |
| Change From Baseline in Weight Changes | 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). | baseline - final visit (32 weeks) |
| Mazze R, Strock E, Morgan B, Wesley D, Bergenstal R, Cuddihy R. Diurnal glucose patterns of exenatide once weekly: a 1-year study using continuous glucose monitoring with ambulatory glucose profile analysis. Endocr Pract. 2009 May-Jun;15(4):326-34. doi: 10.4158/EP09046.ORR. |
| BG002 | 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 |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG002 |
| 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 |
|
|
| Secondary | Change From Baseline in Incidence of Hypoglycemia (Frequency) | 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) | Posted | Mean | Standard Deviation | episodes/day | baseline to final visit (32 weeks) |
|
|
|
| Secondary | Change From Baseline in Incidence of Hypoglycemia (Degree) | 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) | Posted | Mean | Standard Deviation | percentage of measures under 70 mg/dL | baseline to final visit (32 weeks) |
|
|
|
| Secondary | Change From Baseline in Glucose Stability (Absolute Hourly Rate of Change in Median Curve) | 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 | Posted | Mean | Standard Deviation | mg/dL/hr | baseline to final visit (32 weeks) |
|
|
|
| Secondary | Change From Baseline in CGM Glucose Variability | 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). | Posted | Mean | Standard Deviation | mg/dL | baseline to final visit (32 weeks) |
|
|
|
| Secondary | Change From Baseline in Glucose Exposure (Area Under the Diurnal Median Curve or AUC) | 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 | Posted | Mean | Standard Deviation | mg/dL*24hr | baseline - final visit (32 weeks) |
|
|
|
| Secondary | Change From Baseline in Weight Changes | 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). | Posted | Mean | Standard Deviation | lbs (pounds) | baseline - final visit (32 weeks) |
|
|
|
| 0 |
| 20 |
| 20 |
| 20 |
| EG001 | Insulin Glargine | .1 unit per kg to start, titrated based on Continuous Glucose Monitoring results Insulin Glargine: refer to Arm detail | 0 | 20 | 10 | 20 |
| EG002 | 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 | 0 | 20 | 13 | 20 |
|
| Allergic reaction | Immune system disorders | Systematic Assessment | Allergic reaction |
|
| Itching | Skin and subcutaneous tissue disorders | Systematic Assessment | Itching at the injection sites. Persisted through end of study. |
|
| diarrhea | Gastrointestinal disorders | Systematic Assessment | Symptoms resolved on their own. |
|
| Hypoglycemia | Endocrine disorders | Systematic Assessment |
|
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| D014118 |
| Toxins, Biological |
| D001685 | Biological Factors |
| D049528 | Insulin, Long-Acting |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |