Trial Outcomes & Findings for DPP4 Inhibition & Beta Cell Function (NCT NCT02683187)

Last Updated: 2021-05-03

Results Overview

The investigators will use the mean increment of insulin secretion rate above baseline in the 30 minutes after Arginine stimulation to integrate insulin secretion, the primary outcome measure, and 2-way ANOVA with and without Sitagliptin and Ex-9/saline at the two factors.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

40 participants

Primary outcome timeframe

30 minutes

Results posted on

2021-05-03

Participant Flow

Subjects were recruited by advertisement from March 2017 to March 2018.

Participant milestones

Participant milestones
Measure	Sitagliptin and Non-Sitagliptin Arms of study per sequence: 1\. Sitagliptin and Ex-9 then Saline then Non-Sitagliptin and Ex-9 then Saline 2. Sitagliptin and Saline then Ex-9 then Non-Sitagliptin and Ex-9 then Saline 3. Sitagliptin and Ex-9 then Saline then Non-Sitagliptin and Saline then Ex-9 4. Sitagliptin and Saline then Ex-9 then Non-Sitagliptin and Saline then Ex-9 5. Non-Sitagliptin and Ex-9 then Saline then Sitagliptin and Ex-9 then Saline 6. Non-Sitagliptin and Ex-9 then Saline then Sitagliptin and Saline then Ex-9 7. Non-Sitagliptin and Saline then Ex-9 then Sitagliptin and Ex-9 then Saline 8. Non-Sitagliptin and Saline then Ex-9 then Sitagliptin and Saline then Ex-9 .
Overall Study STARTED	40
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitagliptin and Non-Sitagliptin Arms of study per sequence: 1\. Sitagliptin and Ex-9 then Saline then Non-Sitagliptin and Ex-9 then Saline 2. Sitagliptin and Saline then Ex-9 then Non-Sitagliptin and Ex-9 then Saline 3. Sitagliptin and Ex-9 then Saline then Non-Sitagliptin and Saline then Ex-9 4. Sitagliptin and Saline then Ex-9 then Non-Sitagliptin and Saline then Ex-9 5. Non-Sitagliptin and Ex-9 then Saline then Sitagliptin and Ex-9 then Saline 6. Non-Sitagliptin and Ex-9 then Saline then Sitagliptin and Saline then Ex-9 7. Non-Sitagliptin and Saline then Ex-9 then Sitagliptin and Ex-9 then Saline 8. Non-Sitagliptin and Saline then Ex-9 then Sitagliptin and Saline then Ex-9 .
Overall Study Failed IV access	3
Overall Study Withdrawal by Subject	5

Baseline Characteristics

DPP4 Inhibition & Beta Cell Function

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin and Non-Sitagliptin Recipients n=35 Participants The infusion procedures performed during study visits 2 and 3 are identical except that the oral medicine Sitagliptin will only be administered at one of the two visits, with order of Sitagliptin administration determined at random by study staff. Active Comparator: Sitagliptin: Subjects will receive sitagliptin prior to the start of the experiment involving 1/2 of the subjects receiving Exendin-9 (a GLP-1 receptor blocker) first over 60 minutes ; followed by a bolus arginine (5g) infusion after 30 minutes into the Ex-9 infusion, with blood draws over the next 30 minutes. Followed by a 60 minute washout and the procedure is repeated , this time with saline instead of Ex-9 (these procedures are reversed - saline first then Ex-9 - half of the time). Placebo Comparator - No Sitagliptin: Subjects will receive Placebo (instead of sitagliptin) prior to the start of the experiment involving 1/2 of the subjects receiving Exendin-9 (a GLP-1 receptor blocker) first over 60 minutes ; followed by a bolus arginine (5g) infusion after 30 minutes into the Ex-9 infusion, with blood draws over the next 30 minutes. Followed by a 60 minute washout and the procedure is repeated , this time with saline instead of Ex-9 (these procedures are reversed - saline first then Ex-9 - half of the time).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	35 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	51 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	35 Participants n=5 Participants
Diabetes Type No Diabetes (NDM)	20 Participants n=5 Participants
Diabetes Type Type 2 Diabetes (T2DM)	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: 30 minutes

Population: Participants who completed infusion protocols.

Outcome measures

Outcome measures
Measure	Sitagliptin and Ex-9/Saline (Non-diabetics) n=19 Participants The infusion procedures performed during study visits 2 and 3 are identical except that the oral medicine Sitagliptin will only be administered at one of the two visits, with order of Sitagliptin administration determined at random by study staff. In this arm, Sitagliptin will be administered. Active Comparator: Sitagliptin: Subjects will receive sitagliptin prior to the start of the experiment involving 1/2 of the subjects receiving Exendin-9 (a GLP-1 receptor blocker) first over 60 minutes ; followed by a bolus arginine (5g) infusion after 30 minutes into the Ex-9 infusion, with blood draws over the next 30 minutes. Followed by a 60 minute washout and the procedure is repeated , this time with saline instead of Ex-9 (these procedures are reversed - saline first then Ex-9 - half of the time).	Sitagliptin and Ex-9/Saline (Diabetics) n=13 Participants The infusion procedures performed during study visits 2 and 3 are identical except that the oral medicine Sitagliptin will only be administered at one of the two visits, with order of Sitagliptin administration determined at random by study staff. In this arm, Sitagliptin will be administered. Active Comparator: Sitagliptin: Subjects will receive sitagliptin prior to the start of the experiment involving 1/2 of the subjects receiving Exendin-9 (a GLP-1 receptor blocker) first over 60 minutes ; followed by a bolus arginine (5g) infusion after 30 minutes into the Ex-9 infusion, with blood draws over the next 30 minutes. Followed by a 60 minute washout and the procedure is repeated , this time with saline instead of Ex-9 (these procedures are reversed - saline first then Ex-9 - half of the time).	Non-Sitagliptin and Ex-9/Saline (Non-diabetics) n=19 Participants The infusion procedures performed during study visits 2 and 3 are identical except that the oral medicine Sitagliptin will only be administered at one of the two visits, with order of Sitagliptin administration determined at random by study staff. In this arm, placebo will be administered Placebo Comparator - No Sitagliptin: Subjects will receive Placebo (instead of sitagliptin) prior to the start of the experiment involving 1/2 of the subjects receiving Exendin-9 (a GLP-1 receptor blocker) first over 60 minutes ; followed by a bolus arginine (5g) infusion after 30 minutes into the Ex-9 infusion, with blood draws over the next 30 minutes. Followed by a 60 minute washout and the procedure is repeated , this time with saline instead of Ex-9 (these procedures are reversed - saline first then Ex-9 - half of the time).	Non-Sitagliptin and Ex-9/Saline (Diabetics) n=13 Participants The infusion procedures performed during study visits 2 and 3 are identical except that the oral medicine Sitagliptin will only be administered at one of the two visits, with order of Sitagliptin administration determined at random by study staff. In this arm, placebo will be administered Placebo Comparator - No Sitagliptin: Subjects will receive Placebo (instead of sitagliptin) prior to the start of the experiment involving 1/2 of the subjects receiving Exendin-9 (a GLP-1 receptor blocker) first over 60 minutes ; followed by a bolus arginine (5g) infusion after 30 minutes into the Ex-9 infusion, with blood draws over the next 30 minutes. Followed by a 60 minute washout and the procedure is repeated , this time with saline instead of Ex-9 (these procedures are reversed - saline first then Ex-9 - half of the time).
Arginine-stimulated Insulin Secretion With and Without GLP-1 Blockade With GLP-1 Blockade	320.1 pmol/L Standard Error 0.37	243.4 pmol/L Standard Error 0.38	280 pmol/L Standard Error 0.37	251.2 pmol/L Standard Error 0.38
Arginine-stimulated Insulin Secretion With and Without GLP-1 Blockade Without GLP-1 Blockade	318.7 pmol/L Standard Error 0.37	319.4 pmol/L Standard Error 0.38	371.4 pmol/L Standard Error 0.37	249.2 pmol/L Standard Error 0.38

Adverse Events

Sitagliptin

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Non-Sitagliptin

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Sitagliptin n=35 participants at risk The infusion procedures performed during study visits 2 and 3 are identical except that the oral medicine Sitagliptin will only be administered at one of the two visits, with order of Sitagliptin administration determined at random by study staff. In this arm, Sitagliptin will be administered. Active Comparator: Sitagliptin: Subjects will receive sitagliptin prior to the start of the experiment involving 1/2 of the subjects receiving Exendin-9 (a GLP-1 receptor blocker) first over 60 minutes ; followed by a bolus arginine (5g) infusion after 30 minutes into the Ex-9 infusion, with blood draws over the next 30 minutes. Followed by a 60 minute washout and the procedure is repeated , this time with saline instead of Ex-9 (these procedures are reversed - saline first then Ex-9 - half of the time).	Non-Sitagliptin n=34 participants at risk The infusion procedures performed during study visits 2 and 3 are identical except that the oral medicine Sitagliptin will only be administered at one of the two visits, with order of Sitagliptin administration determined at random by study staff. In this arm, placebo will be administered Placebo Comparator - No Sitagliptin: Subjects will receive Placebo (instead of sitagliptin) prior to the start of the experiment involving 1/2 of the subjects receiving Exendin-9 (a GLP-1 receptor blocker) first over 60 minutes ; followed by a bolus arginine (5g) infusion after 30 minutes into the Ex-9 infusion, with blood draws over the next 30 minutes. Followed by a 60 minute washout and the procedure is repeated , this time with saline instead of Ex-9 (these procedures are reversed - saline first then Ex-9 - half of the time).
Blood and lymphatic system disorders failed IV line	8.6% 3/35 • Number of events 3 • 1 month Presented by intervention. One subject did not receive placebo infusion.	5.9% 2/34 • Number of events 2 • 1 month Presented by intervention. One subject did not receive placebo infusion.

Additional Information

Dr. David D'Alessio

Duke University Medical Center

Phone: 919-684-5778

Email: david.d'[email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place