Exenatide Versus Glimepiride in Patients With Type 2 Diabetes

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients meeting defined failure of HbA1c control (primary endpoint) in Study Period II were eligible for entry to Study Period III

Reporting Groups

	Description
Period II, Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
Period III, Exen + Met + Glim - Randomized	Glimepiride once daily, started at 1 mg dose and titrated up to maintenance doses, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
Period III, Exen + Met + Pio or Rosi - Randomized	Oral Rosiglitazone or Pioglitazone once or twice daily, started 15 mg per day, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
Period III, Glim + Met + Exen - Not Randomized	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
Period II, Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin

Participant Flow for 3 periods

Period 1:   Period II

	Period II, Glim + Met	Period III, Exen + Met + Glim - Randomized	Period III, Exen + Met + Pio or Rosi - Randomized	Period III, Glim + Met + Exen - Not Randomized	Period II, Exen + Met
STARTED	514	0	0	0	515
Intent to Treat (ITT) Safety Population	508	0	0	0	511
ITT Efficacy Population	487	0	0	0	490
Met Primary Endpoint	262	0	0	0	203
Without Treatment Failure	124	0	0	0	138
COMPLETED	386	0	0	0	341
NOT COMPLETED	128	0	0	0	174
Adverse Event	17	0	0	0	49
Protocol Violation	18	0	0	0	11
Physician Decision	17	0	0	0	23
Death	2	0	0	0	4
Lack of Efficacy	11	0	0	0	8
Lost to follow up	5	0	0	0	5
Entry Criteria Not Met	8	0	0	0	4
Subject Decision	50	0	0	0	70

Period 2:   Period III

	Period II, Glim + Met	Period III, Exen + Met + Glim - Randomized	Period III, Exen + Met + Pio or Rosi - Randomized	Period III, Glim + Met + Exen - Not Randomized	Period II, Exen + Met
STARTED	0	77	77	166	0
Extension ITT Safety Population	0	74	76	166	0
Extension ITT Efficacy Population	0	73	75	164	0
COMPLETED	0	48	47	101	0
NOT COMPLETED	0	29	30	65	0
Protocol Violation	0	5	3	8	0
Adverse Event	0	3	4	10	0
Physician Decision	0	5	9	15	0
Lack of Efficacy	0	7	5	9	0
Lost to follow up	0	1	1	2	0
Entry Criteria Not Met	0	1	0	1	0
Subject Decision	0	7	8	20	0

Period 3:   Period I

	Period II, Glim + Met	Period III, Exen + Met + Glim - Randomized	Period III, Exen + Met + Pio or Rosi - Randomized	Period III, Glim + Met + Exen - Not Randomized	Period II, Exen + Met
STARTED	0	0	0	0	0
COMPLETED	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Exen + Met	Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
Glim + Met	Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
Total	Total of all reporting groups

Baseline Measures

	Exen + Met	Glim + Met	Total
Overall Participants Analyzed  [Units: Participants]	490	487	977
Age  [Units: Participants]
<=18 years	0	0	0
Between 18 and 65 years	388	389	777
>=65 years	102	98	200
Age  [Units: Years] Mean (Standard Deviation)	56.1  (10.03)	56.8  (9.14)	56.4  (9.60)
Gender  [Units: Participants]
Female	218	235	453
Male	272	252	524
Glycosylated hemoglobin (HbA1c)  [Units: Percentage of total hemoglobin] Mean (Standard Deviation)	7.4  (0.69)	7.4  (0.71)	7.4  (0.70)
Weight  [Units: Kg] Mean (Standard Deviation)	92.8  (16.70)	91.1  (14.78)	92.0  (15.78)

1.  Primary:

Number of Patients With Treatment Failure   [ Time Frame: Baseline to end of Period II (up to 4.5 years) ]

2.  Primary:

Time to Treatment Failure   [ Time Frame: Baseline to end of Period II (up to 4.5 years) ]

3.  Secondary:

Homeostasis Model Assessment of Beta-cell Function (HOMA-B) at Year 3   [ Time Frame: Year 3 in Period II ]

4.  Secondary:

Change in HOMA-B From Baseline to Endpoint   [ Time Frame: Baseline, end of Period II (up to 4.5 years) ]

5.  Secondary:

Fasting Proinsulin/Insulin Ratio at Year 3   [ Time Frame: Year 3 in Period II ]

6.  Secondary:

Change in Fasting Proinsulin/Insulin Ratio From Baseline to Endpoint.   [ Time Frame: Baseline, end of Period II (up to 4.5 years) ]

7.  Secondary:

Ratio of the 30 Minute Increment in Plasma Insulin Concentration and the 30 Minute Increment in Plasma Glucose During the Oral Glucose Tolerance Test (DI30/DG30 Ratio) at Year 3   [ Time Frame: Year 3 in Period II ]

8.  Secondary:

Change in DI30/DG30 Ratio From Baseline to Endpoint   [ Time Frame: Baseline, end of Period II (up to 4.5 years) ]

9.  Secondary:

Disposition Index at Year 3   [ Time Frame: Year 3 in Period II ]

10.  Secondary:

Change in Disposition Index From Baseline to Endpoint   [ Time Frame: Baseline, end of Period II (up to 4.5 years) ]

11.  Secondary:

Change in HbA1c From Baseline to Year 3   [ Time Frame: Baseline, Year 3 in Period II ]

12.  Secondary:

Change in HbA1c From Baseline to Endpoint   [ Time Frame: Baseline, end of Period II (up to 4.5 years) ]

13.  Secondary:

Fasting Plasma Glucose at Year 3   [ Time Frame: Year 3 in Period II ]

14.  Secondary:

Change in Fasting Plasma Glucose From Baseline to Endpoint   [ Time Frame: Baseline, end of Period II (up to 4.5 years) ]

15.  Secondary:

Postprandial (2 Hours) Plasma Glucose at Year 3   [ Time Frame: Year 3 in Period II ]

16.  Secondary:

Change in Postprandial (2 Hours) Plasma Glucose From Baseline to Endpoint   [ Time Frame: Baseline, end of Period II (up to 4.5 years) ]

17.  Secondary:

Change in Body Weight From Baseline to Year 3   [ Time Frame: Baseline, Year 3 in Period II ]

18.  Secondary:

Systolic Blood Pressure at Year 3   [ Time Frame: Year 3 in Period II ]

19.  Secondary:

Diastolic Blood Pressure at Year 3   [ Time Frame: Year 3 in Period II ]

20.  Secondary:

Heart Rate at Year 3   [ Time Frame: Year 3 in Period II ]

21.  Secondary:

Triglycerides at Year 3   [ Time Frame: Year 3 in Period II ]

22.  Secondary:

Total Cholesterol at Year 3   [ Time Frame: Year 3 in Period II ]

23.  Secondary:

High-density Lipoprotein (HDL) Cholesterol at Year 3   [ Time Frame: Year 3 in Period II ]

24.  Secondary:

Hypoglycemia Rate Per Year   [ Time Frame: Baseline to end of Period II (up to 4.5 years) ]

25.  Secondary:

Change in HbA1c From Baseline to Year 2 for Patients Randomized at Entry in Period III   [ Time Frame: Baseline in Period III, Year 2 in Period III ]

26.  Secondary:

Change in HbA1c From Baseline to Year 2 for Patients Not Randomized at Entry in Period III   [ Time Frame: Baseline in Period III, Year 2 in Period III ]

27.  Secondary:

Hypoglycemia Rate Per Year in Period III   [ Time Frame: Start of Period III to end of study ]

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Only patients who reached primary endpoint 12 months or more before the projected end of the study could enter period III.