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

Sponsor
Helsinki University Central Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT02765399
Collaborator
Göteborg University (Other)
23
1
2
48.9
0.5

Study Details

Study Description

Brief Summary

This study aims to evaluate the mechanisms underlying the effect of incretin therapy on lipoprotein metabolism in subjects with type 2 diabetes and to study the effect of liraglutide on hepatic de novo lipogenesis.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

The well recognized dyslipidemia in people with type 2 diabetes consists of high fasting and non-fasting plasma triglycerides (TG), low high-density lipoprotein (HDL) -cholesterol and preponderance of small dense low-density lipoprotein (LDL) particles nominated as the atherogenic lipid triad. Humans are mostly in a postprandial rather than fasting state and therefore non-fasting TG values reflect more accurately the continuous exposure of arterial wall to triglyceride rich lipoproteins (TRLs) and more importantly, to substantial cholesterol load that these particles deliver.

Postprandial lipemia is highly prevalent even in type 2 diabetes patients with normal fasting TG concentrations. Intestinal overproduction of chylomicrons (CMs) and the structural protein apolipoprotein (apo)-B48 has been identified as an integral feature of postprandial lipemia in type 2 diabetes and insulin resistance. It is clinically important to elucidate the mechanism for delayed postprandial lipemia and the interactions between dysglycemia and dyslipidemia in type 2 diabetes patients.

Study Design

Study Type:
Interventional
Actual Enrollment :
23 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
The Effect of Liraglutide Treatment on Postprandial Chylomicron and VLDL Kinetics, Liver Fat and de Novo Lipogenesis - a Single-center Randomized Controlled Study
Actual Study Start Date :
Feb 1, 2015
Actual Primary Completion Date :
Feb 28, 2019
Actual Study Completion Date :
Feb 28, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Liraglutide
Other Names:
  • Victoza
  • Placebo Comparator: 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.

    Drug: Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Change in Liver Fat Content [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.

    2. Plasma Triglyceride (TG) Area Under Curve (AUC) [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.

    3. Body Weight [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.

    4. Change in HbA1c Level [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.

    5. Change in fP-glucose Level [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.

    6. Change in Insulin Level [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.

    7. Change in Matsuda Index [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.

    8. Change in VAT Area [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.

    9. Change in SAT Area [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.

    10. Change in ApoCIII Level [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.

    Secondary Outcome Measures

    1. Change in Hepatic de Novo Lipogenesis [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.

    2. Change in Systolic RR [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.

    3. Mean Total Production of apoB48 [Baseline and after 16 weeks]

      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.

    4. Mean Production Rate of apoB48 in CM [Baseline and after 16 weeks]

      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.

    5. Mean apoB48 FTR to VLDL1 Particles [Baseline and after 16 weeks]

      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.

    6. Mean TG Fractional Catabolic Rates in CM [Baseline and after 16 weeks]

      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.

    7. Mean CM FDC of apoB48 [Baseline and after 16 weeks]

      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.

    8. Change in Direct CM-apoB48 Clearance [Baseline and after 16 weeks]

      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.

    9. Mean CM-apoB48 Transfer Rates to VLDL1 [Baseline and after 16 weeks]

      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.

    10. Mean VLDL1-TG Production Rates [Baseline and after16 weeks]

      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.

    11. Mean Fractional Catabolic Rate of VLDL2-apoB100 [Baseline and after 16 weeks]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    30 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Subjects with type 2 diabetes treated with a lifestyle or metformin (any dose)

    • waist circumference > 88 cm in women and > 92 cm in men

    • BMI 27-40 kg/m2

    • triglycerides between 1.0 - 4.0 mmol/L

    • LDL < 4.5 mmol/l

    Exclusion Criteria:
    • Type 1 diabetes

    • Apo E2/2 phenotype

    • ALT/AST > 3x ULN

    • GFR < 60 ml/min, clinically significant TSH outside normal range

    • Lipid-lowering drugs other than statins within 6 months

    • Current treatment with pioglitazone, insulin, sulphonylureas, gliptins, glinides, SGLT-2 inhibitors or thiazide diuretics (at a dose of > 25 mg / day)

    • Blood pressure > 160 mmHg systolic and/or > 105 diastolic

    • History of pancreatitis or stomach / other major bleeding, thyroid neoplasia, persistent hypothyroidism or persistent hyperthyroidism

    • Any medical condition that puts the patient in the risk of dehydration

    • Concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study.

    • Females of childbearing potential who are not using adequate contraceptive methods

    • Subjects who have experienced side-effects previously from GLP-1 agonists

    • Non-compliance or withdrawal of consent

    • Any information or clinical event described in liraglutide SPC that is a contraindication for the use of liraglutide

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Helsinki University Central Hospital Helsinki Finland 00029

    Sponsors and Collaborators

    • Helsinki University Central Hospital
    • Göteborg University

    Investigators

    • Principal Investigator: Niina Matikainen, MD, PhD, Senior Endocrinologist

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Niina Matikainen, Senior Endocrinologist, Helsinki University Central Hospital
    ClinicalTrials.gov Identifier:
    NCT02765399
    Other Study ID Numbers:
    • LIRA
    First Posted:
    May 6, 2016
    Last Update Posted:
    Apr 12, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details 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).
    Pre-assignment Detail
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Period Title: Overall Study
    STARTED 16 7
    COMPLETED 15 7
    NOT COMPLETED 1 0

    Baseline Characteristics

    Arm/Group Title Liraglutide Placebo Total
    Arm/Group Description 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 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 of all reporting groups
    Overall Participants 16 7 23
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    16
    100%
    7
    100%
    23
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    2
    12.5%
    4
    57.1%
    6
    26.1%
    Male
    14
    87.5%
    3
    42.9%
    17
    73.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    White
    16
    100%
    7
    100%
    23
    100%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    Finland
    16
    100%
    7
    100%
    23
    100%

    Outcome Measures

    1. Primary Outcome
    Title Change in Liver Fat Content
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 15 7
    Baseline
    14.8
    (7.4)
    16.1
    (9.3)
    16 weeks
    10.7
    (6.3)
    13.9
    (9.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.028
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    2. Primary Outcome
    Title Plasma Triglyceride (TG) Area Under Curve (AUC)
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 15 7
    Baseline
    22.0
    (7.4)
    17.5
    (4.8)
    16 weeks
    17.1
    (5.0)
    19.0
    (6.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.011
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.612
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    3. Primary Outcome
    Title Body Weight
    Description Before vs after intervention (Liraglutide or placebo): Change in body weight. Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 15 7
    Baseline
    98.6
    (11.0)
    92.0
    (7.4)
    16 weeks
    96.1
    (11.2)
    89.8
    (6.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.128
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    4. Primary Outcome
    Title Change in HbA1c Level
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 15 7
    Baseline
    7.0
    (1.0)
    6.3
    (0.3)
    16 weeks
    6.4
    (0.7)
    6.4
    (0.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.343
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    5. Primary Outcome
    Title Change in fP-glucose Level
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 15 7
    Baseline
    8.3
    (2.4)
    6.5
    (0.8)
    16 weeks
    6.4
    (1.2)
    6.4
    (0.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.865
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    6. Primary Outcome
    Title Change in Insulin Level
    Description 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.
    Time Frame Baseline and after16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 15 7
    Baseline
    13.9
    (4.8)
    13.8
    (6.9)
    16 weeks
    14.5
    (4.9)
    14.1
    (5.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.532
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.735
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    7. Primary Outcome
    Title Change in Matsuda Index
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 15 7
    Baseline
    2.5
    (1.0)
    3.1
    (1.7)
    16 weeks
    3.5
    (1.8)
    3.1
    (1.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.753
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    8. Primary Outcome
    Title Change in VAT Area
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 15 7
    Baseline
    3403
    (941)
    2710
    (836)
    16 weeks
    3185
    (1014)
    2600
    (825)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.047
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.499
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    9. Primary Outcome
    Title Change in SAT Area
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 15 7
    Baseline
    4043
    (1129)
    5400
    (1598)
    16 weeks
    3792
    (1185)
    5161
    (1653)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.128
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    10. Primary Outcome
    Title Change in ApoCIII Level
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 15 7
    Baseline
    12.0
    (4.4)
    9.7
    (2.8)
    16 weeks
    9.9
    (3.7)
    8.6
    (1.8)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.018
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.578
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    11. Secondary Outcome
    Title Change in Hepatic de Novo Lipogenesis
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 15 7
    Baseline
    15.4
    (7.4)
    12.6
    (7.5)
    16 weeks
    19.1
    (13.1)
    13.8
    (11.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.152
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.866
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    12. Secondary Outcome
    Title Change in Systolic RR
    Description Before vs after intervention (Liraglutide or placebo): systolic blood pressure measurements. Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 15 7
    Baseline
    135
    (14)
    145
    (10)
    16 weeks
    139
    (11)
    137
    (11)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.173
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.018
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    13. Secondary Outcome
    Title Mean Total Production of apoB48
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    18 subjects only volunteered to the kinetic study.
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 14 4
    Baseline
    490
    (190)
    570
    (68)
    16 weeks
    329
    (140)
    530
    (120)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 1
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    14. Secondary Outcome
    Title Mean Production Rate of apoB48 in CM
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    18 subjects only volunteered to the kinetic study.
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 14 4
    Baseline
    284
    (130)
    190
    (35)
    16 weeks
    113
    (53)
    160
    (57)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.79
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    15. Secondary Outcome
    Title Mean apoB48 FTR to VLDL1 Particles
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    18 subjects only volunteered to the kinetic study.
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 14 4
    Baseline
    12
    (4)
    34
    (12)
    16 weeks
    26
    (13)
    30
    (10)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.13
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    16. Secondary Outcome
    Title Mean TG Fractional Catabolic Rates in CM
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    18 subjects only volunteered to the kinetic study.
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 14 4
    Baseline
    33
    (13)
    64
    (15)
    16 weeks
    46
    (20)
    59
    (12)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.011
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.13
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    17. Secondary Outcome
    Title Mean CM FDC of apoB48
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    18 subjects only volunteered to the kinetic study.
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 14 4
    Baseline
    9
    (5)
    4.4
    (1.6)
    16 weeks
    0.8
    (0.4)
    3.2
    (2.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.13
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    18. Secondary Outcome
    Title Change in Direct CM-apoB48 Clearance
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    18 subjects only volunteered to the kinetic study.
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 14 4
    Baseline
    106
    (63)
    20
    (3.8)
    16 weeks
    3.8
    (2.5)
    17
    (12)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.79
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    19. Secondary Outcome
    Title Mean CM-apoB48 Transfer Rates to VLDL1
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    18 subjects only volunteered to the kinetic study.
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 14 4
    Baseline
    127
    (120)
    170
    (38)
    16 weeks
    110
    (57)
    150
    (50)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.79
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    20. Secondary Outcome
    Title Mean VLDL1-TG Production Rates
    Description 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.
    Time Frame Baseline and after16 weeks

    Outcome Measure Data

    Analysis Population Description
    18 subjects only volunteered to the kinetic study.
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 14 4
    Baseline
    51
    (21)
    43
    (1.7)
    16 weeks
    35
    (9.8)
    35
    (10)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.18
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    21. Secondary Outcome
    Title Mean Fractional Catabolic Rate of VLDL2-apoB100
    Description 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.
    Time Frame Baseline and after 16 weeks

    Outcome Measure Data

    Analysis Population Description
    18 subjects only volunteered to the kinetic study.
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    Measure Participants 14 4
    Baseline
    6.7
    (2.6)
    4.5
    (2)
    16 weeks
    5.6
    (2.2)
    5.1
    (2.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Liraglutide
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.068
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.63
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments

    Adverse Events

    Time Frame During 16 weeks of Liraglutide therapy
    Adverse Event Reporting Description
    Arm/Group Title Liraglutide Placebo
    Arm/Group Description 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 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.
    All Cause Mortality
    Liraglutide Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/16 (0%) 0/7 (0%)
    Serious Adverse Events
    Liraglutide Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/16 (0%) 0/7 (0%)
    Other (Not Including Serious) Adverse Events
    Liraglutide Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/16 (25%) 1/7 (14.3%)
    General disorders
    Nausea 4/16 (25%) 1/7 (14.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Prof. Marja-Riitta Taskinen
    Organization Helsinki University and Helsinki University Hospital
    Phone +358-9-47171990
    Email marja-riitta.taskinen@helsinki.fi
    Responsible Party:
    Niina Matikainen, Senior Endocrinologist, Helsinki University Central Hospital
    ClinicalTrials.gov Identifier:
    NCT02765399
    Other Study ID Numbers:
    • LIRA
    First Posted:
    May 6, 2016
    Last Update Posted:
    Apr 12, 2022
    Last Verified:
    Apr 1, 2022