Trial Outcomes & Findings for Title: Therapeutic Targets in African-American Youth With Type 2 Diabetes (NCT NCT02960659)

NCT ID: NCT02960659

Last Updated: 2023-08-01

Results Overview

Gluconeogenesis is measured using stable isotope tracers and is reported as mg/kg lean body mass (LBM) per minute

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 24 participants
• Primary outcome timeframe: Baseline to 12 weeks
• Results posted on: 2023-08-01

Participant Flow

Participant milestones

Measure	Metformin Standard release metformin (500 mg tablets) was initiated and titrated to maximum dose of metformin 1000 mg twice daily over 3 weeks and continued for 12 weeks Metformin: Metformin 500mg oral tablet	Metformin and Liraglutide Standard release metformin (500 mg tablets) and liraglutide (0.6mg) were initiated and titrated to maximum dose of metformin 1000 mg twice daily, and liraglutide 1.8 mg daily over 3 weeks and continued for 12 weeks Liraglutide: Liraglutide (6mg/ml, 3ml ) solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6mg, 1.2mg or 1.8mg. Metformin: Metformin 500mg oral tablet
Overall Study STARTED	13	11
Overall Study COMPLETED	12	10
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Metformin Standard release metformin (500 mg tablets) was initiated and titrated to maximum dose of metformin 1000 mg twice daily over 3 weeks and continued for 12 weeks Metformin: Metformin 500mg oral tablet	Metformin and Liraglutide Standard release metformin (500 mg tablets) and liraglutide (0.6mg) were initiated and titrated to maximum dose of metformin 1000 mg twice daily, and liraglutide 1.8 mg daily over 3 weeks and continued for 12 weeks Liraglutide: Liraglutide (6mg/ml, 3ml ) solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6mg, 1.2mg or 1.8mg. Metformin: Metformin 500mg oral tablet
Overall Study Withdrawal by Subject	1	0
Overall Study Poor compliance	0	1

Baseline Characteristics

This measurement is not available for two participant who withdrew and for one additional participant in the combination group due to technical difficulties

Baseline characteristics by cohort

Measure	Metformin n=13 Participants Standard release metformin (500 mg tablets) was initiated and titrated to maximum dose of metformin 1000 mg twice daily over 3 weeks and continued for 12 weeks Metformin: Metformin 500mg oral tablet	Metformin and Liraglutide n=11 Participants Standard release metformin (500 mg tablets) and liraglutide (0.6mg) were initiated and titrated to maximum dose of metformin 1000 mg twice daily, and liraglutide 1.8 mg daily over 3 weeks and continued for 12 weeks Liraglutide: Liraglutide (6mg/ml, 3ml ) solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6mg, 1.2mg or 1.8mg. Metformin: Metformin 500mg oral tablet	Total n=24 Participants Total of all reporting groups
Age, Continuous	15.6 Years STANDARD_DEVIATION 2.1 • n=13 Participants	15.0 Years STANDARD_DEVIATION 2.1 • n=11 Participants	15.3 Years STANDARD_DEVIATION 2.1 • n=24 Participants
Sex: Female, Male Female	8 Participants n=13 Participants	7 Participants n=11 Participants	15 Participants n=24 Participants
Sex: Female, Male Male	5 Participants n=13 Participants	4 Participants n=11 Participants	9 Participants n=24 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=13 Participants	0 Participants n=11 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Asian	0 Participants n=13 Participants	0 Participants n=11 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=13 Participants	0 Participants n=11 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Black or African American	13 Participants n=13 Participants	11 Participants n=11 Participants	24 Participants n=24 Participants
Race (NIH/OMB) White	0 Participants n=13 Participants	0 Participants n=11 Participants	0 Participants n=24 Participants
Race (NIH/OMB) More than one race	0 Participants n=13 Participants	0 Participants n=11 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=13 Participants	0 Participants n=11 Participants	0 Participants n=24 Participants
Region of Enrollment United States	13 participants n=13 Participants	11 participants n=11 Participants	24 participants n=24 Participants
Body mass index (BMI)	41.6 kg/m^2 STANDARD_DEVIATION 7.3 • n=13 Participants	38.2 kg/m^2 STANDARD_DEVIATION 8.0 • n=11 Participants	40.0 kg/m^2 STANDARD_DEVIATION 7.7 • n=24 Participants
Absolute gluconeogenesis	1.86 mg/kg LBM/min STANDARD_DEVIATION 0.34 • n=11 Participants • This measurement is not available for two participant who withdrew and for one additional participant in the combination group due to technical difficulties	1.75 mg/kg LBM/min STANDARD_DEVIATION 0.36 • n=10 Participants • This measurement is not available for two participant who withdrew and for one additional participant in the combination group due to technical difficulties	1.81 mg/kg LBM/min STANDARD_DEVIATION 0.34 • n=21 Participants • This measurement is not available for two participant who withdrew and for one additional participant in the combination group due to technical difficulties

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Population: Data are missing for one patient in the Metformin group due to technical difficulties

Gluconeogenesis is measured using stable isotope tracers and is reported as mg/kg lean body mass (LBM) per minute

Outcome measures

Measure	Metformin n=11 Participants Standard release metformin (500 mg tablets) was initiated and titrated to maximum dose of metformin 1000 mg twice daily over 3 weeks and continued for 12 weeks Metformin: Metformin 500mg oral tablet	Metformin and Liraglutide n=10 Participants Standard release metformin (500 mg tablets) and liraglutide (0.6mg) were initiated and titrated to maximum dose of metformin 1000 mg twice daily, and liraglutide 1.8 mg daily over 3 weeks and continued for 12 weeks Liraglutide: Liraglutide (6mg/ml, 3ml ) solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6mg, 1.2mg or 1.8mg. Metformin: Metformin 500mg oral tablet
Change in Absolute Gluconeogenesis From Baseline to 12 Weeks	0.018 mg/kg LBM/min Standard Deviation 0.34	-0.050 mg/kg LBM/min Standard Deviation 0.24

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: Data are missing for one patient in the Metformin group due to technical difficulties

Glucose production rate is measured using stable isotope tracers and is reported as mg/kg LBM per minute.

Outcome measures

Measure	Metformin n=11 Participants Standard release metformin (500 mg tablets) was initiated and titrated to maximum dose of metformin 1000 mg twice daily over 3 weeks and continued for 12 weeks Metformin: Metformin 500mg oral tablet	Metformin and Liraglutide n=10 Participants Standard release metformin (500 mg tablets) and liraglutide (0.6mg) were initiated and titrated to maximum dose of metformin 1000 mg twice daily, and liraglutide 1.8 mg daily over 3 weeks and continued for 12 weeks Liraglutide: Liraglutide (6mg/ml, 3ml ) solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6mg, 1.2mg or 1.8mg. Metformin: Metformin 500mg oral tablet
Change in Glucose Production Rate From Baseline to 12 Weeks	0.089 mg/kg LBM/min Standard Deviation 0.28	-0.101 mg/kg LBM/min Standard Deviation 0.24

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: Data are missing for 3 patients in the Metformin group due to technical difficulties

Change in glucose-dependent insulinotropic polypeptide (GIP) AUC during OGTT and meal absorption

Outcome measures

Measure	Metformin n=9 Participants Standard release metformin (500 mg tablets) was initiated and titrated to maximum dose of metformin 1000 mg twice daily over 3 weeks and continued for 12 weeks Metformin: Metformin 500mg oral tablet	Metformin and Liraglutide n=10 Participants Standard release metformin (500 mg tablets) and liraglutide (0.6mg) were initiated and titrated to maximum dose of metformin 1000 mg twice daily, and liraglutide 1.8 mg daily over 3 weeks and continued for 12 weeks Liraglutide: Liraglutide (6mg/ml, 3ml ) solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6mg, 1.2mg or 1.8mg. Metformin: Metformin 500mg oral tablet
Change in GIP AUC During OGTT and Meal Absorption	-4432 pg*ml/min Standard Deviation 10550	-1476 pg*ml/min Standard Deviation 11798

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Change in Glucagon-like peptide-1 (GLP-1) area under the curve concentrations (AUC) during OGTT and meal absorption. These data cannot be reported at this time due to problems with the assay. It is expected that a new assay will be available by May 2024

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: Data are missing for 3 patients in the Metformin group due to technical difficulties

Whole body insulin sensitivity is estimated from a model of glucose and insulin values obtained during the OGTT and is measured in 10^-4 mU/ml/min

Outcome measures

Measure	Metformin n=9 Participants Standard release metformin (500 mg tablets) was initiated and titrated to maximum dose of metformin 1000 mg twice daily over 3 weeks and continued for 12 weeks Metformin: Metformin 500mg oral tablet	Metformin and Liraglutide n=10 Participants Standard release metformin (500 mg tablets) and liraglutide (0.6mg) were initiated and titrated to maximum dose of metformin 1000 mg twice daily, and liraglutide 1.8 mg daily over 3 weeks and continued for 12 weeks Liraglutide: Liraglutide (6mg/ml, 3ml ) solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6mg, 1.2mg or 1.8mg. Metformin: Metformin 500mg oral tablet
Change in Whole Body Insulin Sensitivity From Baseline to 12 Weeks	0.023 10^-4 mU/ml/min Standard Deviation 0.045	0.020 10^-4 mU/ml/min Standard Deviation 0.106

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: Data are missing for one patient in the Metformin group due to technical difficulties

The Hepatic Insulin Sensitivity Index(HISI) is the reciprocal of glucose rate of appearance [1000/(μmol/min)] X insulin concentration [mU/L]

Outcome measures

Measure	Metformin n=11 Participants Standard release metformin (500 mg tablets) was initiated and titrated to maximum dose of metformin 1000 mg twice daily over 3 weeks and continued for 12 weeks Metformin: Metformin 500mg oral tablet	Metformin and Liraglutide n=10 Participants Standard release metformin (500 mg tablets) and liraglutide (0.6mg) were initiated and titrated to maximum dose of metformin 1000 mg twice daily, and liraglutide 1.8 mg daily over 3 weeks and continued for 12 weeks Liraglutide: Liraglutide (6mg/ml, 3ml ) solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6mg, 1.2mg or 1.8mg. Metformin: Metformin 500mg oral tablet
Change in Hepatic Insulin Sensitivity Index From Baseline to 12 Weeks	0.86 1000mU/L/(μmol/min) Standard Deviation 1.50	0.46 1000mU/L/(μmol/min) Standard Deviation 1.42

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: Data are missing for 3 patients in the Metformin group and one patient in the combination group due to technical difficulties

Change in insulin AUC as derived from 2-hour oral glucose tolerance test (OGTT). AUC is calculated using a trapezoidal rule. Higher AUC indicates higher insulin secretion

Outcome measures

Measure	Metformin n=9 Participants Standard release metformin (500 mg tablets) was initiated and titrated to maximum dose of metformin 1000 mg twice daily over 3 weeks and continued for 12 weeks Metformin: Metformin 500mg oral tablet	Metformin and Liraglutide n=9 Participants Standard release metformin (500 mg tablets) and liraglutide (0.6mg) were initiated and titrated to maximum dose of metformin 1000 mg twice daily, and liraglutide 1.8 mg daily over 3 weeks and continued for 12 weeks Liraglutide: Liraglutide (6mg/ml, 3ml ) solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6mg, 1.2mg or 1.8mg. Metformin: Metformin 500mg oral tablet
Change in Insulin AUC Concentrations During an OGTT and Meal Absorption	-6381 min*pmol/L Standard Deviation 40108	47831 min*pmol/L Standard Deviation 48143

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: Data are missing for 5 patients in the Metformin group and 5 patients in the combination group due to technical difficulties

Glycerol turnover is measured using stable isotope tracers and is reported as mg/kg LBM per minute.

Outcome measures

Measure	Metformin n=7 Participants Standard release metformin (500 mg tablets) was initiated and titrated to maximum dose of metformin 1000 mg twice daily over 3 weeks and continued for 12 weeks Metformin: Metformin 500mg oral tablet	Metformin and Liraglutide n=5 Participants Standard release metformin (500 mg tablets) and liraglutide (0.6mg) were initiated and titrated to maximum dose of metformin 1000 mg twice daily, and liraglutide 1.8 mg daily over 3 weeks and continued for 12 weeks Liraglutide: Liraglutide (6mg/ml, 3ml ) solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6mg, 1.2mg or 1.8mg. Metformin: Metformin 500mg oral tablet
Change in Glycerol Turnover From Baseline to 12 Weeks	-0.057 mg/kg LBM/min Standard Deviation 0.131	-0.030 mg/kg LBM/min Standard Deviation 0.104

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: Data are missing for 7 patients in the Metformin group and 5 patients in the combination group due to technical difficulties

Palmitate turnover is measured using stable isotope tracers and is reported as mg/kg LBM per minute.

Outcome measures

Measure	Metformin n=5 Participants Standard release metformin (500 mg tablets) was initiated and titrated to maximum dose of metformin 1000 mg twice daily over 3 weeks and continued for 12 weeks Metformin: Metformin 500mg oral tablet	Metformin and Liraglutide n=5 Participants Standard release metformin (500 mg tablets) and liraglutide (0.6mg) were initiated and titrated to maximum dose of metformin 1000 mg twice daily, and liraglutide 1.8 mg daily over 3 weeks and continued for 12 weeks Liraglutide: Liraglutide (6mg/ml, 3ml ) solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6mg, 1.2mg or 1.8mg. Metformin: Metformin 500mg oral tablet
Change in Palmitate Turnover From Baseline to 12 Weeks	0.003 mg/kg LBM/min Standard Deviation 0.24	-0.18 mg/kg LBM/min Standard Deviation 0.21

Adverse Events

Metformin

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Metformin and Liraglutide

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Metformin n=13 participants at risk Standard release metformin (500 mg tablets) was initiated and titrated to maximum dose of metformin 1000 mg twice daily over 3 weeks and continued for 12 weeks Metformin: Metformin 500mg oral tablet	Metformin and Liraglutide n=11 participants at risk Standard release metformin (500 mg tablets) and liraglutide (0.6mg) were initiated and titrated to maximum dose of metformin 1000 mg twice daily, and liraglutide 1.8 mg daily over 3 weeks and continued for 12 weeks Liraglutide: Liraglutide (6mg/ml, 3ml ) solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6mg, 1.2mg or 1.8mg. Metformin: Metformin 500mg oral tablet
Gastrointestinal disorders Abdominal pain	7.7% 1/13 • Number of events 1 • 12 weeks	18.2% 2/11 • Number of events 2 • 12 weeks
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/13 • 12 weeks	9.1% 1/11 • Number of events 1 • 12 weeks
Psychiatric disorders Depression	0.00% 0/13 • 12 weeks	9.1% 1/11 • Number of events 1 • 12 weeks
Gastrointestinal disorders Diarrhea	15.4% 2/13 • Number of events 3 • 12 weeks	18.2% 2/11 • Number of events 2 • 12 weeks
Injury, poisoning and procedural complications Fall	7.7% 1/13 • Number of events 1 • 12 weeks	0.00% 0/11 • 12 weeks
Metabolism and nutrition disorders Hyperglycemia	7.7% 1/13 • Number of events 1 • 12 weeks	9.1% 1/11 • Number of events 1 • 12 weeks
Metabolism and nutrition disorders Hypoglycemia	7.7% 1/13 • Number of events 1 • 12 weeks	27.3% 3/11 • Number of events 4 • 12 weeks
Infections and infestations Infection	0.00% 0/13 • 12 weeks	9.1% 1/11 • Number of events 1 • 12 weeks
Gastrointestinal disorders Nausea	7.7% 1/13 • Number of events 1 • 12 weeks	9.1% 1/11 • Number of events 1 • 12 weeks
Nervous system disorders Syncope	7.7% 1/13 • Number of events 1 • 12 weeks	0.00% 0/11 • 12 weeks
Gastrointestinal disorders Vomiting	0.00% 0/13 • 12 weeks	27.3% 3/11 • Number of events 4 • 12 weeks
Skin and subcutaneous tissue disorders Injection site reaction	0.00% 0/13 • 12 weeks	9.1% 1/11 • Number of events 1 • 12 weeks

Additional Information

Dr. Stephanie Chung

NIDDK

Phone: 301-402-2122

Email: stephanie.chung@nih.gov

Results disclosure agreements

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