The Effect of Liraglutide Treatment on Postprandial Chylomicron and VLDL Kinetics, Liver Fat and de Novo Lipogenesis
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
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:
|
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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
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
- Kernan WN, Inzucchi SE, Viscoli CM, Brass LM, Bravata DM, Shulman GI, McVeety JC, Horwitz RI. Pioglitazone improves insulin sensitivity among nondiabetic patients with a recent transient ischemic attack or ischemic stroke. Stroke. 2003 Jun;34(6):1431-6. Epub 2003 May 1.
- Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999 Sep;22(9):1462-70.
- Zech LA, Grundy SM, Steinberg D, Berman M. Kinetic model for production and metabolism of very low density lipoprotein triglycerides. Evidence for a slow production pathway and results for normolipidemic subjects. J Clin Invest. 1979 Jun;63(6):1262-73.
- LIRA
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
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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
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 |
marja-riitta.taskinen@helsinki.fi |
- LIRA