Effects of Exenatide and Insulin Glargine in Subjects With Type 2 Diabetes

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Primary Purpose

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

exenatide

Insulin glargine

Metformin

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring diabetes, exenatide, exendin-4, Amylin, Lilly

Eligibility Criteria

30 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis of type 2 diabetes, but otherwise healthy HbA1c between 6.6% and 9.5%, inclusive. Body mass index (BMI) of 25 kg/m2 to 40 kg/m2, inclusive. Treated with a stable dose of metformin for at least 2 months prior to screening. Exclusion Criteria: Patients previously in a study using exenatide. Treated with oral anti-diabetic medications other than metformin within 2 months of screening (thiazolidinediones within 5 months of screening). Treated with insulin within 3 months of screening.

Sites / Locations

Research Site
Research Site
Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Exenatide Arm

Insulin Glargine Arm

Arm Description

Exenatide and Metformin

Insulin Glargine and Metformin

Outcomes

Primary Outcome Measures

Beta-cell Function After 52 Weeks of Therapy

Treatment effect on beta-cell function as measured by the ratio of Week 52 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 52 divided by arginine-stimulated insulin secretion at baseline [week -2]).

Secondary Outcome Measures

Beta-cell Function 4 Weeks After Cessation of Therapy

Treatment effect on beta-cell function as measured by the ratio of Week 56 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 56 divided by arginine-stimulated insulin secretion at baseline [week -2]).

Change in First Phase C-peptide Release

Ratio of first phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to first phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline [week -2]). C-peptide is measured as a surrogate marker of insulin secretion. First phase C-peptide/insulin release is measured during the first ten minutes of glucose infusion during a hyperglycemic clamp procedure.

Change in Second Phase C-peptide Release

Ratio of second phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to second phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline [week -2]). C-peptide is measured as a surrogate marker of insulin secretion. Second phase C-peptide/insulin release is measured from time=10 minutes to time=80 minutes of glucose infusion during a hyperglycemic clamp procedure.

Change in Glycosylated Hemoglobin (HbA1c)

Change in HbA1c from week 0 to week 52 (i.e., HbA1c at week 52 minus HbA1c at week 0).

Change in Fasting Plasma Glucose

Change in fasting plasma glucose from week 0 to week 52 (i.e., fasting plasma glucose at week 52 minus fasting plasma glucose at week 0).

Seven Point Self Monitored Blood Glucose (SMBG) Measurements

SMBG measured at 7 time points (before and after breakfast, before and after lunch, before and after dinner, at bedtime).

Change in Body Weight

Change in body weight from week 0 to week 52 (i.e., body weight at week 52 minus body weight at week 0).

M-value at Baseline, Week 52 and Week 56

M-value at baseline (week -2), week 52 (end of on-drug period), and week 56 (during off-drug period). Insulin sensitivity was assessed during the euglycemic/hyperglycemic clamp test at baseline (week -2), week 52, and week 56. Insulin-mediated glucose uptake (M-value) was calculated as the mean glucose requirement during the 90-120 minute interval of the clamp.

Full Information

NCT ID

NCT00097500

First Posted

November 24, 2004

Last Updated

March 19, 2015

Sponsor

AstraZeneca

Collaborators

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00097500

Brief Title

Effects of Exenatide and Insulin Glargine in Subjects With Type 2 Diabetes

Official Title

A Phase 3, Randomized, Open Label, Comparator-Controlled, Parallel Group, Multicenter Study to Compare the Effects of Exenatide and Insulin Glargine on Beta Cell Function and Cardiovascular Risk Markers in Subjects With Type 2 Diabetes Treated With Metformin Who Have Not Achieved Target HbA1c

Study Type

Interventional

2. Study Status

Record Verification Date

March 2015

Overall Recruitment Status

Completed

Study Start Date

September 2004 (undefined)

Primary Completion Date

December 2009 (Actual)

Study Completion Date

December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

Collaborators

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

This Phase 3, open-label, multicenter study is designed to compare the effects of exenatide and insulin glargine (Lantus® injection) on beta-cell function in patients with type 2 diabetes mellitus using metformin.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus

Keywords

diabetes, exenatide, exendin-4, Amylin, Lilly

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

69 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Exenatide Arm

Arm Type

Experimental

Arm Description

Exenatide and Metformin

Arm Title

Insulin Glargine Arm

Arm Type

Active Comparator

Arm Description

Insulin Glargine and Metformin

Intervention Type

Drug

Intervention Name(s)

exenatide

Other Intervention Name(s)

Byetta

Intervention Description

subcutaneous injection, titrated up to a maximum of 20mcg three times a day in order to meet defined blood glucose targets

Intervention Type

Drug

Intervention Name(s)

Insulin glargine

Other Intervention Name(s)

Lantus

Intervention Description

subcutaneous injection, once a day, titrated as necessary in order to meet defined blood glucose targets

Intervention Type

Drug

Intervention Name(s)

Metformin

Intervention Description

Patients usual dosage

Primary Outcome Measure Information:

Title

Beta-cell Function After 52 Weeks of Therapy

Description

Treatment effect on beta-cell function as measured by the ratio of Week 52 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 52 divided by arginine-stimulated insulin secretion at baseline [week -2]).

Time Frame

Baseline (week -2) and 52 weeks

Secondary Outcome Measure Information:

Title

Beta-cell Function 4 Weeks After Cessation of Therapy

Description

Treatment effect on beta-cell function as measured by the ratio of Week 56 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 56 divided by arginine-stimulated insulin secretion at baseline [week -2]).

Time Frame

Baseline (week -2) and 56 weeks

Title

Change in First Phase C-peptide Release

Description

Ratio of first phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to first phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline [week -2]). C-peptide is measured as a surrogate marker of insulin secretion. First phase C-peptide/insulin release is measured during the first ten minutes of glucose infusion during a hyperglycemic clamp procedure.

Time Frame

baseline (week -2), 52 weeks, and 56 weeks

Title

Change in Second Phase C-peptide Release

Description

Ratio of second phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to second phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline [week -2]). C-peptide is measured as a surrogate marker of insulin secretion. Second phase C-peptide/insulin release is measured from time=10 minutes to time=80 minutes of glucose infusion during a hyperglycemic clamp procedure.

Time Frame

baseline (-2 weeks), 52 weeks, and 56 weeks

Title

Change in Glycosylated Hemoglobin (HbA1c)

Description

Change in HbA1c from week 0 to week 52 (i.e., HbA1c at week 52 minus HbA1c at week 0).

Time Frame

Week 0 and week 52

Title

Change in Fasting Plasma Glucose

Description

Change in fasting plasma glucose from week 0 to week 52 (i.e., fasting plasma glucose at week 52 minus fasting plasma glucose at week 0).

Time Frame

0 weeks and 52 weeks

Title

Seven Point Self Monitored Blood Glucose (SMBG) Measurements

Description

SMBG measured at 7 time points (before and after breakfast, before and after lunch, before and after dinner, at bedtime).

Time Frame

0 weeks and 52 weeks

Title

Change in Body Weight

Description

Change in body weight from week 0 to week 52 (i.e., body weight at week 52 minus body weight at week 0).

Time Frame

0 weeks and 52 weeks

Title

M-value at Baseline, Week 52 and Week 56

Description

M-value at baseline (week -2), week 52 (end of on-drug period), and week 56 (during off-drug period). Insulin sensitivity was assessed during the euglycemic/hyperglycemic clamp test at baseline (week -2), week 52, and week 56. Insulin-mediated glucose uptake (M-value) was calculated as the mean glucose requirement during the 90-120 minute interval of the clamp.

Time Frame

baseline (week -2), 52 weeks, and 56 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Diagnosis of type 2 diabetes, but otherwise healthy HbA1c between 6.6% and 9.5%, inclusive. Body mass index (BMI) of 25 kg/m2 to 40 kg/m2, inclusive. Treated with a stable dose of metformin for at least 2 months prior to screening. Exclusion Criteria: Patients previously in a study using exenatide. Treated with oral anti-diabetic medications other than metformin within 2 months of screening (thiazolidinediones within 5 months of screening). Treated with insulin within 3 months of screening.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Vice President, Research and Development, MD

Organizational Affiliation

Amylin Pharmaceuticals, LLC.

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

Helsinki

Country

Finland

Facility Name

Research Site

City

Amsterdam

Country

Netherlands

Facility Name

Research Site

City

Goteborg

Country

Sweden

12. IPD Sharing Statement

Citations:

PubMed Identifier

19196887

Citation

Bunck MC, Diamant M, Corner A, Eliasson B, Malloy JL, Shaginian RM, Deng W, Kendall DM, Taskinen MR, Smith U, Yki-Jarvinen H, Heine RJ. One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care. 2009 May;32(5):762-8. doi: 10.2337/dc08-1797. Epub 2009 Feb 5.

Results Reference

result

PubMed Identifier

31078666

Citation

Muskiet MHA, Bunck MC, Heine RJ, Corner A, Yki-Jarvinen H, Eliasson B, Joles JA, Diamant M, Tonneijck L, van Raalte DH. Exenatide twice-daily does not affect renal function or albuminuria compared to titrated insulin glargine in patients with type 2 diabetes mellitus: A post-hoc analysis of a 52-week randomised trial. Diabetes Res Clin Pract. 2019 Jul;153:14-22. doi: 10.1016/j.diabres.2019.05.001. Epub 2019 May 9.

Results Reference

derived

PubMed Identifier

21868779

Citation

Bunck MC, Corner A, Eliasson B, Heine RJ, Shaginian RM, Taskinen MR, Smith U, Yki-Jarvinen H, Diamant M. Effects of exenatide on measures of beta-cell function after 3 years in metformin-treated patients with type 2 diabetes. Diabetes Care. 2011 Sep;34(9):2041-7. doi: 10.2337/dc11-0291.

Results Reference

derived

PubMed Identifier

20494360

Citation

Bunck MC, Corner A, Eliasson B, Heine RJ, Shaginian RM, Wu Y, Yan P, Smith U, Yki-Jarvinen H, Diamant M, Taskinen MR. One-year treatment with exenatide vs. insulin glargine: effects on postprandial glycemia, lipid profiles, and oxidative stress. Atherosclerosis. 2010 Sep;212(1):223-9. doi: 10.1016/j.atherosclerosis.2010.04.024. Epub 2010 Apr 29.

Results Reference

derived

Type 2 Diabetes Mellitus

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial