Trial Outcomes & Findings for Efficacy of Exenatide Once Weekly and Once-Daily Insulin Glargine in Patients With Type 2 Diabetes Treated With Metformin Alone or in Combination With Sulfonylurea (DURATION - 3) (NCT NCT00641056)

NCT ID: NCT00641056

Last Updated: 2015-06-15

Results Overview

Change in HbA1c from baseline to Week 26

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 467 participants
• Primary outcome timeframe: Baseline, Week 26
• Results posted on: 2015-06-15

Participant Flow

Participant milestones

Measure	Exenatide Once Weekly Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.
Overall Study STARTED	233	234
Overall Study Intent to Treat (ITT)	233	223
Overall Study COMPLETED	204	209
Overall Study NOT COMPLETED	29	25

Reasons for withdrawal

Measure	Exenatide Once Weekly Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.
Overall Study Adverse Event	12	2
Overall Study Lost to Follow-up	2	1
Overall Study Physician Decision	3	1
Overall Study Protocol Violation	2	0
Overall Study Entry Criteria Not Met	3	0
Overall Study Subject Decision	6	19
Overall Study Sponsor Decision	1	2

Baseline Characteristics

Efficacy of Exenatide Once Weekly and Once-Daily Insulin Glargine in Patients With Type 2 Diabetes Treated With Metformin Alone or in Combination With Sulfonylurea (DURATION - 3)

Baseline characteristics by cohort

Measure	Exenatide Once Weekly n=233 Participants Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine n=223 Participants Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.	Total n=456 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	184 Participants n=5 Participants	167 Participants n=7 Participants	351 Participants n=5 Participants
Age, Categorical >=65 years	49 Participants n=5 Participants	56 Participants n=7 Participants	105 Participants n=5 Participants
Age, Continuous	57.6 years STANDARD_DEVIATION 9.72 • n=5 Participants	58.3 years STANDARD_DEVIATION 9.08 • n=7 Participants	57.9 years STANDARD_DEVIATION 9.41 • n=5 Participants
Sex: Female, Male Female	113 Participants n=5 Participants	100 Participants n=7 Participants	213 Participants n=5 Participants
Sex: Female, Male Male	120 Participants n=5 Participants	123 Participants n=7 Participants	243 Participants n=5 Participants
Glycosylated hemoglobin (HbA1c)	8.32 percentage of total hemoglobin STANDARD_DEVIATION 1.094 • n=5 Participants	8.29 percentage of total hemoglobin STANDARD_DEVIATION 1.020 • n=7 Participants	8.31 percentage of total hemoglobin STANDARD_DEVIATION 1.057 • n=5 Participants
Weight	91.22 kg STANDARD_DEVIATION 18.582 • n=5 Participants	90.56 kg STANDARD_DEVIATION 16.348 • n=7 Participants	90.90 kg STANDARD_DEVIATION 17.509 • n=5 Participants
Background Oral Antidiabetic Agent (OAD) Metformin (Met)	164 participants n=5 Participants	157 participants n=7 Participants	321 participants n=5 Participants
Background Oral Antidiabetic Agent (OAD) Met+Sulfonylurea (SU)	69 participants n=5 Participants	66 participants n=7 Participants	135 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: ITT Population: All randomized patients who had taken at least one dose of study drug. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Change in HbA1c from baseline to Week 26

Outcome measures

Measure	Exenatide Once Weekly n=205 Participants Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine n=206 Participants Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.	Exenatide Once Weekly No SU Patients assigned to the Exenatide Once Weekly No SU group received a 2 mg dose of exenatide injected once a week and took concomitant Met only.	Insulin Glargine No SU Patients assigned to the Insulin Glargine No SU group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L and took concomitant Met only.
Change in HbA1c From Baseline to Week 26	-1.47 percentage of total hemoglobin Standard Error 0.05	-1.31 percentage of total hemoglobin Standard Error 0.06	—	—

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Population. Only patients with baseline HbA1c \> 7% were included in calculation. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Percentage of patients achieving HbA1c <=7.0% at Week 26 (for patients with HbA1c >7% at baseline)

Outcome measures

Measure	Exenatide Once Weekly n=209 Participants Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine n=207 Participants Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.	Exenatide Once Weekly No SU Patients assigned to the Exenatide Once Weekly No SU group received a 2 mg dose of exenatide injected once a week and took concomitant Met only.	Insulin Glargine No SU Patients assigned to the Insulin Glargine No SU group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L and took concomitant Met only.
Percentage of Patients Achieving HbA1c <=7.0% at Week 26	62.2 percentage of patients	54.1 percentage of patients	—	—

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Population. Only patients with baseline HbA1c \> 6.5% were included in calculation. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Percentage of patients achieving HbA1c <=6.5% at Week 26 (for patients with HbA1c >6.5% at baseline)

Outcome measures

Measure	Exenatide Once Weekly n=227 Participants Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine n=218 Participants Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.	Exenatide Once Weekly No SU Patients assigned to the Exenatide Once Weekly No SU group received a 2 mg dose of exenatide injected once a week and took concomitant Met only.	Insulin Glargine No SU Patients assigned to the Insulin Glargine No SU group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L and took concomitant Met only.
Percentage of Patients Achieving HbA1c <=6.5% at Week 26	43.2 percentage of patients	28.4 percentage of patients	—	—

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Change in FSG (mmol/L) from Baseline to Week 26

Outcome measures

Measure	Exenatide Once Weekly n=192 Participants Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine n=197 Participants Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.	Exenatide Once Weekly No SU Patients assigned to the Exenatide Once Weekly No SU group received a 2 mg dose of exenatide injected once a week and took concomitant Met only.	Insulin Glargine No SU Patients assigned to the Insulin Glargine No SU group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L and took concomitant Met only.
Change in Fasting Serum Glucose (FSG) From Baseline to Week 26	-2.13 mmol/L Standard Error 0.16	-2.76 mmol/L Standard Error 0.16	—	—

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Change in BW (kg) from Baseline to Week 26

Outcome measures

Measure	Exenatide Once Weekly n=207 Participants Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine n=209 Participants Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.	Exenatide Once Weekly No SU Patients assigned to the Exenatide Once Weekly No SU group received a 2 mg dose of exenatide injected once a week and took concomitant Met only.	Insulin Glargine No SU Patients assigned to the Insulin Glargine No SU group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L and took concomitant Met only.
Change in Body Weight (BW) From Baseline to Week 26	-2.63 kg Standard Error 0.20	1.42 kg Standard Error 0.20	—	—

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Change in Total Cholesterol (mmol/L) from Baseline to Week 26

Outcome measures

Measure	Exenatide Once Weekly n=191 Participants Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine n=198 Participants Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.	Exenatide Once Weekly No SU Patients assigned to the Exenatide Once Weekly No SU group received a 2 mg dose of exenatide injected once a week and took concomitant Met only.	Insulin Glargine No SU Patients assigned to the Insulin Glargine No SU group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L and took concomitant Met only.
Change in Total Cholesterol From Baseline to Week 26	-0.12 mmol/L Standard Error 0.06	-0.04 mmol/L Standard Error 0.06	—	—

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Change in HDL (mmol/L) from Baseline to Week 26

Outcome measures

Measure	Exenatide Once Weekly n=191 Participants Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine n=198 Participants Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.	Exenatide Once Weekly No SU Patients assigned to the Exenatide Once Weekly No SU group received a 2 mg dose of exenatide injected once a week and took concomitant Met only.	Insulin Glargine No SU Patients assigned to the Insulin Glargine No SU group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L and took concomitant Met only.
Change in High-density Lipoprotein Cholesterol (HDL) From Baseline to Week 26	-0.00 mmol/L Standard Error 0.01	0.01 mmol/L Standard Error 0.01	—	—

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Ratio of Triglycerides (measured in mmol/L) at Week 26 to Baseline. Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.

Outcome measures

Measure	Exenatide Once Weekly n=191 Participants Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine n=198 Participants Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.	Exenatide Once Weekly No SU Patients assigned to the Exenatide Once Weekly No SU group received a 2 mg dose of exenatide injected once a week and took concomitant Met only.	Insulin Glargine No SU Patients assigned to the Insulin Glargine No SU group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L and took concomitant Met only.
Ratio of Triglycerides at Week 26 to Baseline	0.96 ratio Standard Error 0.03	0.89 ratio Standard Error 0.03	—	—

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: ITT Population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Change in Systolic Blood Pressure (mmHg) and Diastolic Blood Pressure (mmHg) from Baseline to Week 26

Outcome measures

Measure	Exenatide Once Weekly n=233 Participants Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine n=222 Participants Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.	Exenatide Once Weekly No SU Patients assigned to the Exenatide Once Weekly No SU group received a 2 mg dose of exenatide injected once a week and took concomitant Met only.	Insulin Glargine No SU Patients assigned to the Insulin Glargine No SU group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L and took concomitant Met only.
Change in Blood Pressure From Baseline to Week 26 Diastolic Blood Pressure	-1.15 mmHg Standard Deviation 10.08	-0.72 mmHg Standard Deviation 8.73	—	—
Change in Blood Pressure From Baseline to Week 26 Systolic Blood Pressure	-3.03 mmHg Standard Deviation 16.57	-0.63 mmHg Standard Deviation 14.88	—	—

SECONDARY outcome

Timeframe: Baseline to Week 26

Population: ITT Population.

Major hypoglycemia: any episode with symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure with prompt recovery in response to administration of glucagon or glucose or documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) and required the assistance of another person. Minor hypoglycemia: any time a patient felt that he or she was experiencing a sign or symptom of hypoglycemia that was self-treated or resolved on its own and had a blood glucose level <3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia.

Outcome measures

Measure	Exenatide Once Weekly n=69 Participants Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine n=66 Participants Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.	Exenatide Once Weekly No SU n=164 Participants Patients assigned to the Exenatide Once Weekly No SU group received a 2 mg dose of exenatide injected once a week and took concomitant Met only.	Insulin Glargine No SU n=157 Participants Patients assigned to the Insulin Glargine No SU group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L and took concomitant Met only.
Assessment on Event Rate of Treatment-emergent Hypoglycemic Episodes Major Hypoglycemia	0.00 rate per subject-year Standard Error 0.000	0.03 rate per subject-year Standard Error 0.030	0.01 rate per subject-year Standard Error 0.013	0.01 rate per subject-year Standard Error 0.013
Assessment on Event Rate of Treatment-emergent Hypoglycemic Episodes Minor Hypoglycemia	1.14 rate per subject-year Standard Error 0.184	2.66 rate per subject-year Standard Error 0.284	0.10 rate per subject-year Standard Error 0.037	0.63 rate per subject-year Standard Error 0.091

Adverse Events

Exenatide Once Weekly

Serious events: 11 serious events

Other events: 100 other events

Deaths: 0 deaths

Insulin Glargine

Serious events: 10 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Measure	Exenatide Once Weekly n=233 participants at risk Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine n=223 participants at risk Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.
Cardiac disorders Acute coronary syndrome	0.43% 1/233	0.00% 0/223
Cardiac disorders Atrioventricular block	0.43% 1/233	0.00% 0/223
Cardiac disorders Cardiac arrest	0.43% 1/233	0.00% 0/223
Surgical and medical procedures Cardioversion	0.43% 1/233	0.00% 0/223
Nervous system disorders Cerebrovascular accident	0.43% 1/233	0.00% 0/223
General disorders Chest pain	0.43% 1/233	0.90% 2/223
Injury, poisoning and procedural complications Drug exposure during pregnancy	0.43% 1/233	0.00% 0/223
Vascular disorders Haematoma	0.43% 1/233	0.00% 0/223
General disorders Injection site nodule	0.43% 1/233	0.00% 0/223
Cardiac disorders Myocardial ischaemia	0.43% 1/233	0.00% 0/223
Gastrointestinal disorders Oedematous pancreatitis	0.43% 1/233	0.00% 0/223
Infections and infestations Urinary tract infection	0.43% 1/233	0.00% 0/223
Infections and infestations Viral pericarditis	0.43% 1/233	0.00% 0/223
Surgical and medical procedures Vitrectomy	0.43% 1/233	0.00% 0/223
Blood and lymphatic system disorders Anaemia	0.00% 0/233	0.45% 1/223
Hepatobiliary disorders Bile duct stone	0.00% 0/233	0.45% 1/223
Nervous system disorders Carotid artery stenosis	0.00% 0/233	0.45% 1/223
Hepatobiliary disorders Cholecystitis	0.00% 0/233	0.45% 1/223
Surgical and medical procedures Colon polypectomy	0.00% 0/233	0.45% 1/223
Cardiac disorders Myocarditis	0.00% 0/233	0.45% 1/223
Surgical and medical procedures Peripheral nerve transposition	0.00% 0/233	0.45% 1/223
Nervous system disorders Presyncope	0.00% 0/233	0.45% 1/223
Eye disorders Retinal detachment	0.00% 0/233	0.45% 1/223

Other adverse events

Measure	Exenatide Once Weekly n=233 participants at risk Patients assigned to the Exenatide Once Weekly group received a 2 mg dose of exenatide injected once a week.	Insulin Glargine n=223 participants at risk Patients assigned to the Insulin Glargine group started insulin glargine treatment with 10 units per day, utilizing the INITIATE (Initiate Insulin by Aggressive Titration and Education) dosing and were instructed to adjust insulin doses to achieve a target blood glucose of 4.0-5.5 mmol/L.
Infections and infestations Nasopharyngitis	12.9% 30/233	17.5% 39/223
Gastrointestinal disorders Nausea	12.9% 30/233	1.3% 3/223
Nervous system disorders Headache	9.9% 23/233	7.2% 16/223
Gastrointestinal disorders Diarrhoea	8.6% 20/233	3.6% 8/223
General disorders Injection site nodule	5.2% 12/233	0.00% 0/223

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