Trial Outcomes & Findings for The Effect of Liraglutide Treatment on Postprandial Chylomicron and VLDL Kinetics, Liver Fat and de Novo Lipogenesis (NCT NCT02765399)

NCT ID: NCT02765399

Last Updated: 2022-04-12

Results Overview

Before vs after intervention (Liraglutide or placebo): mean liver fat content was measured by magnetic resonance imaging. Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 23 participants
• Primary outcome timeframe: Baseline and after 16 weeks
• Results posted on: 2022-04-12

Participant Flow

In total, 54 subjects were assessed for eligibility, of whom 31 were excluded because of failure to meet inclusion criteria (n = 28) or declining to participate (n = 1), or for other reasons (n = 2).

Participant milestones

Measure	Liraglutide Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Overall Study STARTED	16	7
Overall Study COMPLETED	15	7
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	Liraglutide Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Overall Study Nausea	1	0

Baseline Characteristics

The Effect of Liraglutide Treatment on Postprandial Chylomicron and VLDL Kinetics, Liver Fat and de Novo Lipogenesis

Baseline characteristics by cohort

Measure	Liraglutide n=16 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=7 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.	Total n=23 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	16 Participants n=5 Participants	7 Participants n=7 Participants	23 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	3 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	7 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Finland	16 participants n=5 Participants	7 participants n=7 Participants	23 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and after 16 weeks

Before vs after intervention (Liraglutide or placebo): mean liver fat content was measured by magnetic resonance imaging. Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.

Outcome measures

Measure	Liraglutide n=15 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=7 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Change in Liver Fat Content Baseline	14.8 fat % Standard Deviation 7.4	16.1 fat % Standard Deviation 9.3
Change in Liver Fat Content 16 weeks	10.7 fat % Standard Deviation 6.3	13.9 fat % Standard Deviation 9.7

PRIMARY outcome

Timeframe: Baseline and after 16 weeks

Before vs after intervention (Liraglutide or placebo): postprandial plasma TG summary measured using the trapezoidal rule and expressed as AUC (at fasting and at 0.5, 1, 2, 3, 4, 6 and 8 hours) after oral fat tolerance test. Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.

Outcome measures

Measure	Liraglutide n=15 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=7 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Plasma Triglyceride (TG) Area Under Curve (AUC) Baseline	22.0 mmol/l per h Standard Deviation 7.4	17.5 mmol/l per h Standard Deviation 4.8
Plasma Triglyceride (TG) Area Under Curve (AUC) 16 weeks	17.1 mmol/l per h Standard Deviation 5.0	19.0 mmol/l per h Standard Deviation 6.2

PRIMARY outcome

Timeframe: Baseline and after 16 weeks

Before vs after intervention (Liraglutide or placebo): Change in body weight. Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.

Outcome measures

Measure	Liraglutide n=15 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=7 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Body Weight Baseline	98.6 kg Standard Deviation 11.0	92.0 kg Standard Deviation 7.4
Body Weight 16 weeks	96.1 kg Standard Deviation 11.2	89.8 kg Standard Deviation 6.3

PRIMARY outcome

Timeframe: Baseline and after 16 weeks

Before vs after intervention (Liraglutide or placebo): Change in B -Hemoglobiini-A1c level in plasma. Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.

Outcome measures

Measure	Liraglutide n=15 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=7 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Change in HbA1c Level Baseline	7.0 HbA1c % Standard Deviation 1.0	6.3 HbA1c % Standard Deviation 0.3
Change in HbA1c Level 16 weeks	6.4 HbA1c % Standard Deviation 0.7	6.4 HbA1c % Standard Deviation 0.5

PRIMARY outcome

Timeframe: Baseline and after 16 weeks

Before vs after intervention (Liraglutide or placebo): concentration of fasting plasma glucose measured using the hexokinase method. Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.

Outcome measures

Measure	Liraglutide n=15 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=7 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Change in fP-glucose Level Baseline	8.3 mmol/L Standard Deviation 2.4	6.5 mmol/L Standard Deviation 0.8
Change in fP-glucose Level 16 weeks	6.4 mmol/L Standard Deviation 1.2	6.4 mmol/L Standard Deviation 0.9

PRIMARY outcome

Timeframe: Baseline and after16 weeks

Before vs after intervention (Liraglutide or placebo): Concentration of insulin level in plasma measured using electrochemiluminescence. Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.

Outcome measures

Measure	Liraglutide n=15 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=7 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Change in Insulin Level Baseline	13.9 μU/mL Standard Deviation 4.8	13.8 μU/mL Standard Deviation 6.9
Change in Insulin Level 16 weeks	14.5 μU/mL Standard Deviation 4.9	14.1 μU/mL Standard Deviation 5.5

PRIMARY outcome

Timeframe: Baseline and after 16 weeks

Before vs after intervention (Liraglutide or placebo): Matsuda index was calculated for assessment of insulin sensitivity in plasma at time points 0, 30, 60 and 120 minutes using formula 10,000/square root of [fasting glucose x fasting insulin] x [mean glucose x mean insulin during oral glucose tolerance test]. The Matsuda index is considered to be the gold standard to determine insulin sensitivity without glucose clamp studies (Matsuda M, DeFronzo RA. Diabetes Care. 22:1462-70). Subjects who don't have insulin resistance have values of Matsuda Index of 2.5 or higher (Kerman WN et al. Stroke 34:1431;2003). Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.

Outcome measures

Measure	Liraglutide n=15 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=7 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Change in Matsuda Index Baseline	2.5 index Standard Deviation 1.0	3.1 index Standard Deviation 1.7
Change in Matsuda Index 16 weeks	3.5 index Standard Deviation 1.8	3.1 index Standard Deviation 1.3

PRIMARY outcome

Timeframe: Baseline and after 16 weeks

Before vs after intervention (Liraglutide or placebo): visceral adipose tissue area measured by magnetic resonance imaging (MRI). Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.

Outcome measures

Measure	Liraglutide n=15 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=7 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Change in VAT Area Baseline	3403 cm3 Standard Deviation 941	2710 cm3 Standard Deviation 836
Change in VAT Area 16 weeks	3185 cm3 Standard Deviation 1014	2600 cm3 Standard Deviation 825

PRIMARY outcome

Timeframe: Baseline and after 16 weeks

Before vs after intervention (Liraglutide or placebo): subcutaneous adipose tissue area measured by magnetic resonance imaging (MRI). Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.

Outcome measures

Measure	Liraglutide n=15 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=7 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Change in SAT Area Baseline	4043 cm3 Standard Deviation 1129	5400 cm3 Standard Deviation 1598
Change in SAT Area 16 weeks	3792 cm3 Standard Deviation 1185	5161 cm3 Standard Deviation 1653

PRIMARY outcome

Timeframe: Baseline and after 16 weeks

Before vs after intervention (Liraglutide or placebo): apolipoprotein CIII concentration in plasma measured by using turbidimetric immunoassay. Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.

Outcome measures

Measure	Liraglutide n=15 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=7 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Change in ApoCIII Level Baseline	12.0 mg/dL Standard Deviation 4.4	9.7 mg/dL Standard Deviation 2.8
Change in ApoCIII Level 16 weeks	9.9 mg/dL Standard Deviation 3.7	8.6 mg/dL Standard Deviation 1.8

SECONDARY outcome

Timeframe: Baseline and after 16 weeks

Before vs after intervention (Liraglutide or placebo): Hepatic DNL is calculated from enrichment of deuterated water ingested during the kinetic study at specified time points (0, 4 and 8 hrs.). Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.

Outcome measures

Measure	Liraglutide n=15 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=7 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Change in Hepatic de Novo Lipogenesis Baseline	15.4 μmol/L Standard Deviation 7.4	12.6 μmol/L Standard Deviation 7.5
Change in Hepatic de Novo Lipogenesis 16 weeks	19.1 μmol/L Standard Deviation 13.1	13.8 μmol/L Standard Deviation 11.2

SECONDARY outcome

Timeframe: Baseline and after 16 weeks

Before vs after intervention (Liraglutide or placebo): systolic blood pressure measurements. Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.

Outcome measures

Measure	Liraglutide n=15 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=7 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Change in Systolic RR 16 weeks	139 mm Hg Standard Deviation 11	137 mm Hg Standard Deviation 11
Change in Systolic RR Baseline	135 mm Hg Standard Deviation 14	145 mm Hg Standard Deviation 10

SECONDARY outcome

Timeframe: Baseline and after 16 weeks

Population: 18 subjects only volunteered to the kinetic study.

Before vs after intervention (Liraglutide or placebo): ApoB48 total production in plasma measured by using multicompartmental modeling. The power of mathematical modelling to describe the metabolic pathways of lipid and lipoprotein metabolism was demonstrated by Zech L et al (JCI 63:1262;1979) and have been widely used over 30yrs. So far few studies have focused on the modelling of apo B48 and apo B100 after a meal that is more physiological than the fasting state (Björnson E et al. JIM 285:562;2019). Production rates for apo B48, apo B100 and triglycerides in chylomicrons, VLDL1 and VLDL2 were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90,120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. Analysis of tracer/ tracee curves of stable isotopes was used to derived the estimates of kinetic parameters using a new mathematical modeling per day. Results from Taskinen et al. Diabetes Obes Metab. 23:1191; 2021.

Outcome measures

Measure	Liraglutide n=14 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=4 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Mean Total Production of apoB48 Baseline	490 mg/day Standard Deviation 190	570 mg/day Standard Deviation 68
Mean Total Production of apoB48 16 weeks	329 mg/day Standard Deviation 140	530 mg/day Standard Deviation 120

SECONDARY outcome

Timeframe: Baseline and after 16 weeks

Population: 18 subjects only volunteered to the kinetic study.

Before vs after intervention (Liraglutide or placebo): Change in mean production rate of ApoB48 in chylomicrons isolated from plasma samples and measured by multicompartmental modeling assay. The power of mathematical modelling to describe the metabolic pathways of lipid and lipoprotein metabolism was demonstrated by Zech L et al (JCI 1979). So far few studies have focused on the modelling of apo B48 and apo B100 after a meal that is more physiological than the fasting state (Björnson E et al. JIM 2019). Production rates for apo B48, apo B100 and triglycerides in chylomicrons, VLDL1 and VLDL2 were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90,120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. Analysis of tracer/ tracee curves of stable isotopes was used to derived the estimates of kinetic parameters using a new mathematical modeling per day. Results from Taskinen et al.

Outcome measures

Measure	Liraglutide n=14 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=4 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Mean Production Rate of apoB48 in CM Baseline	284 mg/day Standard Deviation 130	190 mg/day Standard Deviation 35
Mean Production Rate of apoB48 in CM 16 weeks	113 mg/day Standard Deviation 53	160 mg/day Standard Deviation 57

SECONDARY outcome

Timeframe: Baseline and after 16 weeks

Population: 18 subjects only volunteered to the kinetic study.

Before vs after intervention (Liraglutide or placebo): Change in apoB48 chylomicron fractional transfer rate to VLDL1 isolated from plasma by ultracentrifugation and by liquid chromatography/mass spectrometry and calculated with multicompartmental modeling assay. So far few studies have focused on the modelling of apo B48 and apo B100 after a meal that is more physiological than the fasting state (Björnson E et al. JIM 2019). Production rates for apo B48, apo B100 and triglycerides in chylomicrons, VLDL1 and VLDL2 were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90,120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. Analysis of tracer/ tracee curves of stable isotopes was used to derived the estimates of kinetic parameters using a new mathematical modeling per day. Results from Taskinen et al. 2021.

Outcome measures

Measure	Liraglutide n=14 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=4 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Mean apoB48 FTR to VLDL1 Particles Baseline	12 pools/day Standard Deviation 4	34 pools/day Standard Deviation 12
Mean apoB48 FTR to VLDL1 Particles 16 weeks	26 pools/day Standard Deviation 13	30 pools/day Standard Deviation 10

SECONDARY outcome

Timeframe: Baseline and after 16 weeks

Population: 18 subjects only volunteered to the kinetic study.

Before vs after intervention (Liraglutide or placebo): Change in triglycerides fractional catabolic rates in isolated chylomicrons from plasma samples measured by multicompartmental modeling assay. The power of mathematical modelling to describe the metabolic pathways of lipid and lipoprotein metabolism was demonstrated by Zech L et al (JCI 1979). So far few studies have focused on the modelling of apo B48 and apo B100 after a meal that is more physiological than the fasting state (Björnson E et al. JIM 2019). Production rates for apo B48, apo B100 and triglycerides in chylomicrons, VLDL1 and VLDL2 were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90,120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. Analysis of tracer/ tracee curves of stable isotopes was used to derived the estimates of kinetic parameters using a new mathematical modeling per day. Results from Taskinen et al. DOM 2021.

Outcome measures

Measure	Liraglutide n=14 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=4 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Mean TG Fractional Catabolic Rates in CM Baseline	33 pools/day Standard Deviation 13	64 pools/day Standard Deviation 15
Mean TG Fractional Catabolic Rates in CM 16 weeks	46 pools/day Standard Deviation 20	59 pools/day Standard Deviation 12

SECONDARY outcome

Timeframe: Baseline and after 16 weeks

Population: 18 subjects only volunteered to the kinetic study.

Before vs after intervention (Liraglutide or placebo): Change in chylomicron fractional direct clearance rates of apoB48 measured from plasma by liquid chromatography - mass spectrometry with multicompartmental modeling assay. The power of mathematical modelling to describe the metabolic pathways of lipid and lipoprotein metabolism was demonstrated by Zech L et al (1979). So far few studies have focused on the modelling of apo B48 and apo B100 after a meal that is more physiological than the fasting state (Björnson E et al. 2019). Production rates for apo B48, apo B100 and triglycerides in chylomicrons, VLDL1 and VLDL2 were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90,120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. Analysis of tracer/ tracee curves of stable isotopes was used to derived the estimates of kinetic parameters using a new mathematical modeling per day. Results from Taskinen et al. 2021.

Outcome measures

Measure	Liraglutide n=14 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=4 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Mean CM FDC of apoB48 Baseline	9 pools/day Standard Deviation 5	4.4 pools/day Standard Deviation 1.6
Mean CM FDC of apoB48 16 weeks	0.8 pools/day Standard Deviation 0.4	3.2 pools/day Standard Deviation 2.5

SECONDARY outcome

Timeframe: Baseline and after 16 weeks

Population: 18 subjects only volunteered to the kinetic study.

Before vs after intervention (Liraglutide or placebo): Direct apoB48 clearance rates in isolated chylomicrons and measured by liquid chromatography - mass spectrometry and calculated by multicompartmental modeling assay. The power of mathematical modelling to describe the metabolic pathways of lipid and lipoprotein metabolism was demonstrated by Zech L et al (1979). So far few studies have focused on the modelling of apo B48 and apo B100 after a meal that is more physiological than the fasting state (Björnson E et al. 2019). Production rates for apo B48, apo B100 and triglycerides in chylomicrons, VLDL1 and VLDL2 were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90,120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. Analysis of tracer/ tracee curves of stable isotopes was used to derived the estimates of kinetic parameters using a new mathematical modeling per day. Results from Taskinen et al. 2021.

Outcome measures

Measure	Liraglutide n=14 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=4 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Change in Direct CM-apoB48 Clearance Baseline	106 mg/day Standard Deviation 63	20 mg/day Standard Deviation 3.8
Change in Direct CM-apoB48 Clearance 16 weeks	3.8 mg/day Standard Deviation 2.5	17 mg/day Standard Deviation 12

SECONDARY outcome

Timeframe: Baseline and after 16 weeks

Population: 18 subjects only volunteered to the kinetic study.

Before vs after intervention (Liraglutide or placebo): Change in chylomicron-apoB48 transfer rates to VLDL1 isolated from plasma by ultracentrifugation and measured using multicompartmental modeling. The power of mathematical modelling to describe the metabolic pathways of lipid and lipoprotein metabolism was demonstrated by Zech L et al (1979). So far few studies have focused on the modelling of apo B48 and apo B100 after a meal that is more physiological than the fasting state (Björnson E et al. 2019). Production rates for apo B48, apo B100 and triglycerides in chylomicrons, VLDL1 and VLDL2 were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90,120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. Analysis of tracer/ tracee curves of stable isotopes was used to derived the estimates of kinetic parameters using a new mathematical modeling per day. Results from Taskinen et al. 2021.

Outcome measures

Measure	Liraglutide n=14 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=4 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Mean CM-apoB48 Transfer Rates to VLDL1 16 weeks	110 mg/day Standard Deviation 57	150 mg/day Standard Deviation 50
Mean CM-apoB48 Transfer Rates to VLDL1 Baseline	127 mg/day Standard Deviation 120	170 mg/day Standard Deviation 38

SECONDARY outcome

Timeframe: Baseline and after16 weeks

Population: 18 subjects only volunteered to the kinetic study.

Before vs after intervention (Liraglutide or placebo): Change in VLDL1 production rates measured from isolated VLDL from plasma samples by ultracentrifugation and measured using mathematical modeling. The power of mathematical modelling to describe the metabolic pathways of lipid and lipoprotein metabolism was demonstrated by Zech L et al (JCI 1979). So far few studies have focused on the modelling of apo B48 and apo B100 after a meal that is more physiological than the fasting state (Björnson E et al. JIM 2019). Production rates for apo B48, apo B100 and triglycerides in chylomicrons, VLDL1 and VLDL2 were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90,120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. Analysis of tracer/ tracee curves of stable isotopes was used to derived the estimates of kinetic parameters using a new mathematical modeling per day. Results from Taskinen et al. DOM 2021.

Outcome measures

Measure	Liraglutide n=14 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=4 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Mean VLDL1-TG Production Rates Baseline	51 g/day Standard Deviation 21	43 g/day Standard Deviation 1.7
Mean VLDL1-TG Production Rates 16 weeks	35 g/day Standard Deviation 9.8	35 g/day Standard Deviation 10

SECONDARY outcome

Timeframe: Baseline and after 16 weeks

Population: 18 subjects only volunteered to the kinetic study.

Before vs after intervention (Liraglutide or placebo): Change in VLDL2-apoB100 fractional catabolic rates measured from isolated VLDL2 from plasma by ultracentrifugation and measured using mathematical modeling. The power of mathematical modelling to describe the metabolic pathways of lipid and lipoprotein metabolism was demonstrated by Zech L et al (JCI 1979). So far few studies have focused on the modelling of apo B48 and apo B100 after a meal that is more physiological than the fasting state (Björnson E et al. JIM 2019). Production rates for apo B48, apo B100 and triglycerides in chylomicrons, VLDL1 and VLDL2 were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90,120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. Analysis of tracer/ tracee curves of stable isotopes was used to derived the estimates of kinetic parameters using a new mathematical modeling per day. Results from Taskinen et al. DOM 2021.

Outcome measures

Measure	Liraglutide n=14 Participants Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=4 Participants Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
Mean Fractional Catabolic Rate of VLDL2-apoB100 Baseline	6.7 pools/day Standard Deviation 2.6	4.5 pools/day Standard Deviation 2
Mean Fractional Catabolic Rate of VLDL2-apoB100 16 weeks	5.6 pools/day Standard Deviation 2.2	5.1 pools/day Standard Deviation 2.1

Adverse Events

Liraglutide

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Liraglutide n=16 participants at risk Liraglutide subcutaneous injection once daily with following dose escalation: liraglutide 0.6 mg once daily for one week; liraglutide 1.2 mg once daily for one week and thereafter liraglutide 1.8 mg once daily for 3.5 months. Liraglutide	Placebo n=7 participants at risk Placebo subcutaneous injection once daily with following dose escalation: placebo 0.1 ml once daily for one week; placebo 0.2 ml once daily for one week and thereafter placebo 0.3 ml once daily for 3.5 months.
General disorders Nausea	25.0% 4/16 • During 16 weeks of Liraglutide therapy	14.3% 1/7 • During 16 weeks of Liraglutide therapy

Additional Information

Prof. Marja-Riitta Taskinen

Helsinki University and Helsinki University Hospital

Phone: +358-9-47171990

Email: marja-riitta.taskinen@helsinki.fi

Results disclosure agreements

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