Trial Outcomes & Findings for Comparison of the Effect of Exenatide Versus Sitagliptin on 24-hour Average Glucose in Patients With Type 2 Diabetes on Metformin or a Thiazolidinedione (NCT NCT00729326)

NCT ID: NCT00729326

Last Updated: 2015-04-09

Results Overview

Change in time-averaged glucose during a 24-hour period from baseline to endpoint (i.e., time-averaged glucose over 24 hours at endpoint minus time-averaged glucose over 24 hours at baseline).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 83 participants
• Primary outcome timeframe: baseline and 8 Weeks
• Results posted on: 2015-04-09

Participant Flow

Participant milestones

Measure	Exenatide Followed By Sitagliptin Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks. Followed by exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.	Sitagliptin Followed By Exenatide Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks. Followed by exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.
Overall Study STARTED	41	42
Overall Study COMPLETED	31	33
Overall Study NOT COMPLETED	10	9

Reasons for withdrawal

Measure	Exenatide Followed By Sitagliptin Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks. Followed by exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.	Sitagliptin Followed By Exenatide Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks. Followed by exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.
Overall Study Lost to Follow-up	2	0
Overall Study Physician Decision	0	1
Overall Study Protocol Violation	3	2
Overall Study Subject Decision	4	4
Overall Study Sponsor Decision	1	2

Baseline Characteristics

Comparison of the Effect of Exenatide Versus Sitagliptin on 24-hour Average Glucose in Patients With Type 2 Diabetes on Metformin or a Thiazolidinedione

Baseline characteristics by cohort

Measure	Exenatide Followed By Sitagliptin n=41 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks. Followed by exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.	Sitagliptin Followed By Exenatide n=42 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks. Followed by exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Total n=83 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=5 Participants	37 Participants n=7 Participants	71 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Age, Continuous	54.7 years STANDARD_DEVIATION 10.10 • n=5 Participants	53.5 years STANDARD_DEVIATION 9.49 • n=7 Participants	54.1 years STANDARD_DEVIATION 9.75 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	29 Participants n=7 Participants	48 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	13 Participants n=7 Participants	35 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and 8 Weeks

Population: The number of patients was determined based on 90% powering of the study. Analyses were based on data from all randomized patients receiving at least one dose of the study drug and completing at least one treatment period. For each patient, the missing data for some time points were imputed by linear interpolation.

Change in time-averaged glucose during a 24-hour period from baseline to endpoint (i.e., time-averaged glucose over 24 hours at endpoint minus time-averaged glucose over 24 hours at baseline).

Outcome measures

Measure	Exenatide n=67 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=66 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Change in Time-averaged Glucose During a 24 Hour Period	-41.65 mg/dL Standard Error 2.55	-29.56 mg/dL Standard Error 2.58

SECONDARY outcome

Timeframe: baseline and 8 Weeks

Population: All patients in FAS who have both baseline and endpoint measurement; Last Observation Carried Forward

Change in 2 hour post-prandial glucose after the morning meal from baseline to endpoint (i.e., glucose level 2 hours after the morning meal at baseline minus glucose level 2 hours after the morning meal at endpoint)

Outcome measures

Measure	Exenatide n=69 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=68 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Change in Two-hour Postprandial Glucose After the Morning Meal	-108.35 mg/dL Standard Error 4.36	-44.43 mg/dL Standard Error 4.40

SECONDARY outcome

Timeframe: baseline and 8 Weeks

Population: All patients in FAS who have both baseline and endpoint measurement; Last Observation Carried Forward

Change in fasting blood glucose after the morning meal from baseline to endpoint (i.e., fasting blood glucose after the morning meal at baseline minus fasting blood glucose after the morning meal at endpoint)

Outcome measures

Measure	Exenatide n=68 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=67 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Change in Fasting Blood Glucose After the Morning Meal	-28.93 mg/dL Standard Error 2.70	-28.22 mg/dL Standard Error 2.71

SECONDARY outcome

Timeframe: baseline and 8 Weeks

Population: All patients in the FAS who have both baseline and endpoint measurements; Last Observation Carried Forward

Change in Postprandial Glucagon AUC after the morning meal (t=0 to 4 hours) (i.e., Glucagon AUC over the first 4 hours following the morning meal at baseline minus glucagon AUC over the first 4 hours following the morning meal at endpoint)

Outcome measures

Measure	Exenatide n=68 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=67 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Change in Postprandial Glucagon Area Under the Concentration-time Curve (AUC) After the Morning Meal	-29.60 pmol*hours/L Standard Error 2.91	-16.91 pmol*hours/L Standard Error 2.93

SECONDARY outcome

Timeframe: baseline and 8 Weeks

Population: All patients in the FAS who have both baseline and endpoint measurements; Last Observation Carried Forward

Change in postprandial glucagon AUC excursion after the morning meal (t=0 to 4 hours) (i.e., glucagon AUC excursion for 4 hours following the morning meal at baseline minus glucagon AUC excursion for 4 hours following the morning meal at endpoint)

Outcome measures

Measure	Exenatide n=68 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=67 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Change in Postprandial Glucagon AUC Excursion After the Morning Meal	-30.94 pmol*hours/L Standard Error 2.12	-14.93 pmol*hours/L Standard Error 2.13

SECONDARY outcome

Timeframe: baseline and 8 Weeks

Population: All patients in the FAS who have both baseline and endpoint measurements; Last Observation Carried Forward

Change in postprandial triglyceride AUC after the morning meal (t=0 to 4 hours) (i.e., postprandial triglyceride AUC after the morning meal at baseline minus postprandial triglyceride AUC after the morning meal at endpoint)

Outcome measures

Measure	Exenatide n=69 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=68 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Change in Postprandial Triglyceride AUC After the Morning Meal	0.83 mg*hours/dL Standard Error 0.03	0.87 mg*hours/dL Standard Error 0.03

SECONDARY outcome

Timeframe: baseline and 8 Weeks

Population: All patients in the FAS who have both baseline and endpoint measurements; Last Observation Carried Forward

Change in postprandial triglyceride AUC excursion after the morning meal (t=0 to 4 hours) (i.e., postprandial triglyceride AUC excursion after the morning meal at baseline minus postprandial triglyceride AUC excursion after the morning meal at endpoint)

Outcome measures

Measure	Exenatide n=69 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=68 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Change in Postprandial Triglyceride AUC Excursion After the Morning Meal	-108.16 mg*hours/dL Standard Error 8.38	-41.39 mg*hours/dL Standard Error 8.45

SECONDARY outcome

Timeframe: baseline and 8 Weeks

Population: All patients in the FAS who have both baseline and endpoint measurements; Last Observation Carried Forward

Change in postprandial C-peptide AUC after the morning meal (t=0 to 4 hours) (i.e., postprandial C-peptide AUC after the morning meal at baseline minus postprandial C-peptide AUC after the morning meal at endpoint)

Outcome measures

Measure	Exenatide n=69 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=68 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Change in Postprandial C-peptide AUC After the Morning Meal	-1.78 nmol*hours/L Standard Error 0.28	0.25 nmol*hours/L Standard Error 0.28

SECONDARY outcome

Timeframe: baseline and 8 Weeks

Population: All patients in the FAS who have both baseline and endpoint measurements; Last Observation Carried Forward

Change in Postprandial C-peptide AUC excursion after the morning meal (t=0 to 4 hours) (i.e., postprandial C-peptide AUC excursion after the morning meal at baseline minus postprandial C-peptide AUC excursion after the morning meal at endpoint)

Outcome measures

Measure	Exenatide n=69 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=68 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Change in Postprandial C-peptide AUC Excursion After the Morning Meal	-2.83 nmol*hours/L Standard Error 0.29	0.14 nmol*hours/L Standard Error 0.29

SECONDARY outcome

Timeframe: baseline and 8 Weeks

Population: All patients in the FAS who have both baseline and endpoint measurements; Last Observation Carried Forward

Change in postprandial insulin AUC after the morning meal (t=0 to 4 hours) (i.e., postprandial insulin AUC after the morning meal at baseline minus postprandial insulin AUC after the morning meal at endpoint)

Outcome measures

Measure	Exenatide n=69 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=68 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Change in Postprandial Insulin AUC After the Morning Meal	-396.12 pmol*hours/L Standard Error 56.79	-8.79 pmol*hours/L Standard Error 57.32

SECONDARY outcome

Timeframe: baseline and 8 Weeks

Population: All patients in the FAS who have both baseline and endpoint measurements; Last Observation Carried Forward

Change in Postprandial insulin AUC excursion after the morning meal (t=0 to 4 hours) (i.e., postprandial insulin AUC excursion after the morning meal at baseline minus postprandial insulin AUC excursion after the morning meal at endpoint)

Outcome measures

Measure	Exenatide n=69 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=68 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Change in Postprandial Insulin AUC Excursion After the Morning Meal	-525.01 pmol*hours/L Standard Error 58.77	-34.83 pmol*hours/L Standard Error 59.40

SECONDARY outcome

Timeframe: baseline and 8 Weeks

Population: All patients in the FAS who have both baseline and endpoint measurements; Last Observation Carried Forward

Change in Postprandial active GLP-1 AUC after the morning meal (t=0 to 4 hours) (i.e., postprandial active GLP-1 AUC after the morning meal at baseline minus postprandial active GLP-1 AUC after the morning meal at endpoint)

Outcome measures

Measure	Exenatide n=69 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=68 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Change in Postprandial Active GLP-1 AUC After the Morning Meal	-14.28 pmol*hours/L Standard Error 3.12	47.37 pmol*hours/L Standard Error 3.15

SECONDARY outcome

Timeframe: baseline and 8 Weeks

Population: All patients in the FAS who have both baseline and endpoint measurements; Last Observation Carried Forward

Change in Postprandial active GLP-1 AUC excursion after the morning meal (t=0 to 4 hours) (i.e., postprandial active GLP-1 AUC excursion after the morning meal at baseline minus postprandial active GLP-1 AUC excursion after the morning meals at endpoint)

Outcome measures

Measure	Exenatide n=69 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=68 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Change in Postprandial Active GLP-1 AUC Excursion After the Monrning Meal	-14.04 pmol*hours/L Standard Error 3.28	23.53 pmol*hours/L Standard Error 3.31

SECONDARY outcome

Timeframe: 4 Weeks

Population: All patients in FAS

Percentage of patients experiencing minor hypoglycemia with a confirmed glucose <54mg/dL

Outcome measures

Measure	Exenatide n=35 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=37 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Percentage of Patients Experiencing Hypoglycemia (Baseline to Week 4)	2.9 Percentage of patients	2.7 Percentage of patients

SECONDARY outcome

Timeframe: 4 weeks

Population: Full analysis set

Number of episodes of hypoglycemia experienced during the first 4 weeks of the study

Outcome measures

Measure	Exenatide n=35 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=37 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Episodes of Hypoglycemia (Baseline to Week 4)	1 episodes of hypoglycemia	1 episodes of hypoglycemia

SECONDARY outcome

Timeframe: 8 weeks

Population: All patients in FAS

Percentage of patients experiencing minor hypoglycemia with a confirmed glucose <54mg/dL

Outcome measures

Measure	Exenatide n=35 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=34 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Percentage of Patients Experiencing Hypoglycemia (Week 4 to Week 8)	5.7 Percentage of patients	0.0 Percentage of patients

SECONDARY outcome

Timeframe: 8 weeks

Population: All patients in FAS

Number of episodes of hypoglycemia experienced between week 4 and week 8 of the study

Outcome measures

Measure	Exenatide n=35 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=34 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Episodes of Hypoglycemia (Week 4 to Week 8)	2 episodes of hypoglycemia	0 episodes of hypoglycemia

SECONDARY outcome

Timeframe: 4 weeks and 8 weeks

Population: All patients in FAS

Percentage of patients experiencing minor hypoglycemia with a confirmed glucose <54mg/dL

Outcome measures

Measure	Exenatide n=70 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=71 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Percentage of Patients Experiencing Hypoglycemia (Overall)	4.3 Percentage of patients	1.4 Percentage of patients

SECONDARY outcome

Timeframe: 4 weeks and 8 weeks

Population: All patients in FAS

Number of episodes of hypoglycemia experienced overall during the study

Outcome measures

Measure	Exenatide n=70 Participants Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=71 Participants Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Episodes of Hypoglycemia (Overall)	3 episodes of hypoglycemia	1 episodes of hypoglycemia

Adverse Events

Exenatide

Serious events: 2 serious events

Other events: 43 other events

Deaths: 0 deaths

Sitagliptin

Serious events: 0 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Measure	Exenatide n=73 participants at risk Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=73 participants at risk Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Immune system disorders Anaphylactic reaction	1.4% 1/73	0.00% 0/73
Skin and subcutaneous tissue disorders Angioedema	1.4% 1/73	0.00% 0/73
Psychiatric disorders Confusional state	1.4% 1/73	0.00% 0/73

Other adverse events

Measure	Exenatide n=73 participants at risk Exenatide 5mcg plus sitagliptin placebo for 1 week, then exenatide 10mcg plus sitagliptin placebo for 3 weeks.	Sitagliptin n=73 participants at risk Exenatide placebo plus sitagliptin 100mg for 1 week, then exenatide placebo plus sitagliptin 100mg for 3 weeks.
Gastrointestinal disorders Nausea	37.0% 27/73	16.4% 12/73
Gastrointestinal disorders Vomiting	20.5% 15/73	5.5% 4/73
Nervous system disorders Headache	12.3% 9/73	12.3% 9/73
Gastrointestinal disorders Diarrhoea	9.6% 7/73	11.0% 8/73
Nervous system disorders Dizziness	9.6% 7/73	6.8% 5/73
Musculoskeletal and connective tissue disorders Back pain	8.2% 6/73	6.8% 5/73
Gastrointestinal disorders Abdominal discomfort	5.5% 4/73	4.1% 3/73
General disorders Asthenia	5.5% 4/73	1.4% 1/73
Respiratory, thoracic and mediastinal disorders Cough	5.5% 4/73	6.8% 5/73
Gastrointestinal disorders Dyspepsia	5.5% 4/73	1.4% 1/73
Metabolism and nutrition disorders Hypoglycaemia	5.5% 4/73	2.7% 2/73
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.1% 3/73	6.8% 5/73
Respiratory, thoracic and mediastinal disorders Nasal congestion	2.7% 2/73	6.8% 5/73

Additional Information

Peter Ohman, Medical Science Director

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60