Trial Outcomes & Findings for Effect of Chronic Exenatide Therapy on Beta Cell Function and Insulin Sensitivity in T2DM (NCT NCT02981069)

NCT ID: NCT02981069

Last Updated: 2023-07-20

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

90 participants

Primary outcome timeframe

ACUTE [after a single dose of each study drug or placebo]

Results posted on

2023-07-20

Participant Flow

Type 2 diabetes with significant clinical complications were excluded

Participant milestones

Participant milestones
Measure	Byetta / Bydureon Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)	Dapagliflozin 4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg Dapagliflozin: 10mg	Byetta/Bydureon Plus Dapagliflozin Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc PLUS Dapagliflozin: 4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg Dapagliflozin: 10mg Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)	Placebo Placebo group (4 weeks and 12 weeks) Placebo: Placebo for Dapagliflozin
Acute Portion of Study STARTED	25	25	25	15
Acute Portion of Study COMPLETED	25	25	25	15
Acute Portion of Study NOT COMPLETED	0	0	0	0
16 Week Drug Administration Period STARTED	25	25	25	0
16 Week Drug Administration Period COMPLETED	25	25	25	0
16 Week Drug Administration Period NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Chronic Exenatide Therapy on Beta Cell Function and Insulin Sensitivity in T2DM

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Byetta / Bydureon n=25 Participants Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)	Dapagliflozin n=25 Participants 4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg Dapagliflozin: 10mg	Byetta/Bydureon Plus Dapagliflozin n=25 Participants Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc PLUS Dapagliflozin: 4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg Dapagliflozin: 10mg Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)	Placebo n=15 Participants Placebo group (4 weeks and 12 weeks) Placebo: Placebo for Dapagliflozin	Total n=90 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=93 Participants	25 Participants n=4 Participants	23 Participants n=27 Participants	14 Participants n=483 Participants	87 Participants n=36 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	1 Participants n=483 Participants	3 Participants n=36 Participants
Age, Continuous	52 years STANDARD_DEVIATION 3 • n=93 Participants	51 years STANDARD_DEVIATION 2 • n=4 Participants	49 years STANDARD_DEVIATION 4 • n=27 Participants	54 years STANDARD_DEVIATION 3 • n=483 Participants	52 years STANDARD_DEVIATION 3 • n=36 Participants
Sex: Female, Male Female	15 Participants n=93 Participants	12 Participants n=4 Participants	16 Participants n=27 Participants	8 Participants n=483 Participants	51 Participants n=36 Participants
Sex: Female, Male Male	10 Participants n=93 Participants	13 Participants n=4 Participants	9 Participants n=27 Participants	7 Participants n=483 Participants	39 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=93 Participants	19 Participants n=4 Participants	21 Participants n=27 Participants	11 Participants n=483 Participants	67 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=93 Participants	6 Participants n=4 Participants	3 Participants n=27 Participants	2 Participants n=483 Participants	20 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants	3 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	2 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Black or African American	8 Participants n=93 Participants	7 Participants n=4 Participants	6 Participants n=27 Participants	5 Participants n=483 Participants	26 Participants n=36 Participants
Race (NIH/OMB) White	17 Participants n=93 Participants	17 Participants n=4 Participants	19 Participants n=27 Participants	8 Participants n=483 Participants	61 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Region of Enrollment United States	25 participants n=93 Participants	25 participants n=4 Participants	25 participants n=27 Participants	15 participants n=483 Participants	90 participants n=36 Participants

PRIMARY outcome

Timeframe: ACUTE [after a single dose of each study drug or placebo]

Population: Type 2 diabetes

Outcome measures

Outcome measures
Measure	EXENATIDE n=25 Participants Exenatide: After acute exposure to a single dose of Exenatide, 5 mcg.	Dapagliflozin n=25 Participants After acute single dose exposure of Dapagliflozin, Farxiga, 10mg	Exenatide Plus Dapagliflozin n=25 Participants After acute exposure to both dapagliflozin, farxiga 10 mg orally and a single subcutaneous injection of Exenatide	Placebo n=15 Participants After a single dose of placebo
Change in Endogenous Glucose Production (EGP) After Acute Exposure to a Single Dose and Again After 16 Weeks of Treatment	-0.18 mg/kg.min Standard Error 0.02	0.14 mg/kg.min Standard Error 0.03	-0.08 mg/kg.min Standard Error 0.03	-0.03 mg/kg.min Standard Error 0.02

PRIMARY outcome

Timeframe: 16 weeks

Population: Type 2 diabetes

After screening, eligible subjects will receive a measurement of endogenous glucose production (EGP) with a prime-continuous infusion of 3-3H-glucose. The EGP measurement will be performed in the morning after a 10-12 hour overnight fast and will last 8.5 hours (from 6 AM to 2:30 PM). After a 3.5-hour tracer equilibration period, subjects (20 per group) will receive one of the following medications: (i) exenatide 5 ug subcutaneously; (ii) dapagliflozin (10 mg); and (iii) dapagliflozin 10 mg + exenatide 5 ug. Only three groups will be followed for 16 weeks since subjects are diabetic and placebo is not appropriate to use for this period. Again, subjects will be randomized to treatment with either exenatide, dapagliflozin or both drugs in combination. Repeat EGP will be measured again at 16 weeks as described above and data will be compared to respective "acute" studies.

Outcome measures

Outcome measures
Measure	EXENATIDE n=25 Participants Exenatide: After acute exposure to a single dose of Exenatide, 5 mcg.	Dapagliflozin n=25 Participants After acute single dose exposure of Dapagliflozin, Farxiga, 10mg	Exenatide Plus Dapagliflozin n=25 Participants After acute exposure to both dapagliflozin, farxiga 10 mg orally and a single subcutaneous injection of Exenatide	Placebo After a single dose of placebo
Change in Endogenous Glucose Production (EGP) After 16 Weeks of Treatment With Each Study Drug.	-0.23 mg/kg.min Standard Error 0.02	0.20 mg/kg.min Standard Error 0.03	-0.12 mg/kg.min Standard Error 0.03	—

SECONDARY outcome

Timeframe: 16 weeks

Population: type 2 diabetes

The change in (FPG) above baseline following administration of study interventions after 16 weeks of treatment with each study drug(s) compared to data obtained during the acute exposure. Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.

Outcome measures

Outcome measures
Measure	EXENATIDE n=25 Participants Exenatide: After acute exposure to a single dose of Exenatide, 5 mcg.	Dapagliflozin n=25 Participants After acute single dose exposure of Dapagliflozin, Farxiga, 10mg	Exenatide Plus Dapagliflozin n=25 Participants After acute exposure to both dapagliflozin, farxiga 10 mg orally and a single subcutaneous injection of Exenatide	Placebo After a single dose of placebo
Change in Fasting Plasma Glucose (FPG) Concentration	42 mg/dl Standard Error 1	72 mg/dl Standard Error 3	11 mg/dl Standard Error 3	—

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: type 2 diabetes

Measurement of change in plasma glucagon concentration after 16 weeks of treatment with each study drug(s) compared to acute exposure at baseline. Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.

Outcome measures

Outcome measures
Measure	EXENATIDE n=25 Participants Exenatide: After acute exposure to a single dose of Exenatide, 5 mcg.	Dapagliflozin n=25 Participants After acute single dose exposure of Dapagliflozin, Farxiga, 10mg	Exenatide Plus Dapagliflozin n=25 Participants After acute exposure to both dapagliflozin, farxiga 10 mg orally and a single subcutaneous injection of Exenatide	Placebo After a single dose of placebo
Change in Plasma Glucagon Concentration	4 pg/ml Standard Error 2	5 pg/ml Standard Error 2	-6 pg/ml Standard Error 2	—

SECONDARY outcome

Timeframe: Baseline to 16 weeks

Population: Type 2 diabetes

Measurement of change in plasma insulin concentration from baseline to 16 weeks following treatment with each study drug(s). Placebo arm was not included in this 16 week portion of the study, since subjects are diabetic. Only 3 arms of the study were conducted: (i) Byetta/Bydureon, (ii) Dapagliflozin (iii) Byetta/Bydureon plus Dapagliflozin.

Outcome measures

Outcome measures
Measure	EXENATIDE n=25 Participants Exenatide: After acute exposure to a single dose of Exenatide, 5 mcg.	Dapagliflozin n=25 Participants After acute single dose exposure of Dapagliflozin, Farxiga, 10mg	Exenatide Plus Dapagliflozin n=25 Participants After acute exposure to both dapagliflozin, farxiga 10 mg orally and a single subcutaneous injection of Exenatide	Placebo After a single dose of placebo
Change in Plasma Insulin Concentration	-2 microUnits/ml Standard Error 1	-2 microUnits/ml Standard Error 2	3 microUnits/ml Standard Error 2	—

Adverse Events

Byetta / Bydureon

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Dapagliflozin

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Byetta/Bydureon Plus Dapagliflozin

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Byetta / Bydureon n=25 participants at risk Exenatide: 4 weeks of exenatide 5 mcg twice daily followed by Bydureon 2mg sc weekly Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)	Dapagliflozin n=25 participants at risk 16 weeks Dapagliflozin, Farxiga, 10mg Dapagliflozin: 10mg	Byetta/Bydureon Plus Dapagliflozin n=25 participants at risk Exenatide: 4 weeks of exenatide followed by 12 weeks of Bydureon 2mg sc once weekly PLUS Dapagliflozin: 16 weeks Dapagliflozin, Farxiga, 10mg Dapagliflozin: 10mg Exenatide: Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)	Placebo n=15 participants at risk 16 weeks of placebo administration
Reproductive system and breast disorders Genital Mycosis	0.00% 0/25 • Baseline to 6 months Patient reporting and physical exam by principal investigator/nurse coordinator	16.0% 4/25 • Number of events 4 • Baseline to 6 months Patient reporting and physical exam by principal investigator/nurse coordinator	8.0% 2/25 • Number of events 2 • Baseline to 6 months Patient reporting and physical exam by principal investigator/nurse coordinator	0.00% 0/15 • Baseline to 6 months Patient reporting and physical exam by principal investigator/nurse coordinator
Gastrointestinal disorders Nausea and Vomiting	24.0% 6/25 • Number of events 6 • Baseline to 6 months Patient reporting and physical exam by principal investigator/nurse coordinator	0.00% 0/25 • Baseline to 6 months Patient reporting and physical exam by principal investigator/nurse coordinator	20.0% 5/25 • Number of events 5 • Baseline to 6 months Patient reporting and physical exam by principal investigator/nurse coordinator	0.00% 0/15 • Baseline to 6 months Patient reporting and physical exam by principal investigator/nurse coordinator

Additional Information

Professor

University of Texas Health San Antonio

Phone: 12103587200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place