Type 2 DiabetesPhase 4NCT02765399

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

A Phase 4 study testing Liraglutide in people with Type 2 Diabetes, run by Helsinki University Central Hospital at 1 site in Finland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 30 to 75 years
Conditions the study is for: Type 2 Diabetes
What is being tested?: Liraglutide
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 23 participants
Where: 1 siteFinland
Study dates: 1 Feb 2015to 28 Feb 2019
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 30 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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)

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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

Trial locations and contacts

1 site in 1 country.

Finland1 site

Helsinki University Central Hospital
Helsinki, 00029

Other trials in Finland

About this study

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

Read the 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.

Conditions: Type 2 Diabetes
Being tested: Liraglutide, Placebo
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LiraglutideDrug
Also called Victoza
PlaceboDrug

Study groups in NCT02765399
Study group	Role	What they receive
Liraglutide	Experimental	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. Receives: Drug: Liraglutide
Placebo	Placebo comparator	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. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Liver Fat Content
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.
Measured: Baseline and after 16 weeks
Plasma Triglyceride (TG) Area Under Curve (AUC)
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.
Measured: Baseline and after 16 weeks
Body Weight
Before vs after intervention (Liraglutide or placebo): Change in body weight. Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.
Measured: Baseline and after 16 weeks
Change in HbA1c Level
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.
Measured: Baseline and after 16 weeks
Change in fP-glucose Level
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.
Measured: Baseline and after 16 weeks
Change in Insulin Level
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.
Measured: Baseline and after16 weeks
Change in Matsuda Index
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.
Measured: Baseline and after 16 weeks
Change in VAT Area
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.
Measured: Baseline and after 16 weeks
Change in SAT Area
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.
Measured: Baseline and after 16 weeks
Change in ApoCIII Level
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.
Measured: Baseline and after 16 weeks

Secondary outcomes (11)

Change in Hepatic de Novo Lipogenesis
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.
Measured: Baseline and after 16 weeks
Change in Systolic RR
Before vs after intervention (Liraglutide or placebo): systolic blood pressure measurements. Results from Matikainen et al. Diabetes Obes Metab 21:84-94; 2019.
Measured: Baseline and after 16 weeks
Mean Total Production of apoB48
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.
Measured: Baseline and after 16 weeks
Mean Production Rate of apoB48 in CM
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.
Measured: Baseline and after 16 weeks
Mean apoB48 FTR to VLDL1 Particles
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.
Measured: Baseline and after 16 weeks
Mean TG Fractional Catabolic Rates in CM
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.
Measured: Baseline and after 16 weeks
Mean CM FDC of apoB48
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.
Measured: Baseline and after 16 weeks
Change in Direct CM-apoB48 Clearance
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.
Measured: Baseline and after 16 weeks
Mean CM-apoB48 Transfer Rates to VLDL1
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.
Measured: Baseline and after 16 weeks
Mean VLDL1-TG Production Rates
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.
Measured: Baseline and after16 weeks
Mean Fractional Catabolic Rate of VLDL2-apoB100
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.
Measured: Baseline and after 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Feb 201528 Feb 2019

First posted6 May 2016 (estimated)
Study start1 Feb 2015
Primary completion28 Feb 2019
Study completion28 Feb 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
More trials run by Helsinki University Central HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Participant
Enrolment: 23 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02765399
Sponsor's protocol ID: LIRA
Status last verified: Apr 2022
First submitted: 2 May 2016
Last updated: 12 Apr 2022
Results posted: Yes, on ClinicalTrials.gov
Individual data sharing: No

Publications

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. doi: 10.1172/JCI109421.
PubMed 221537
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. doi: 10.2337/diacare.22.9.1462.
PubMed 10480510
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. doi: 10.1161/01.STR.0000071108.00234.0E. Epub 2003 May 1.
PubMed 12730556
Matikainen N, Soderlund S, Bjornson E, Pietilainen K, Hakkarainen A, Lundbom N, Taskinen MR, Boren J. Liraglutide treatment improves postprandial lipid metabolism and cardiometabolic risk factors in humans with adequately controlled type 2 diabetes: A single-centre randomized controlled study. Diabetes Obes Metab. 2019 Jan;21(1):84-94. doi: 10.1111/dom.13487. Epub 2018 Sep 4.
PubMed 30073766
Taskinen MR, Bjornson E, Matikainen N, Soderlund S, Pietilainen KH, Ainola M, Hakkarainen A, Lundbom N, Fuchs J, Thorsell A, Andersson L, Adiels M, Packard CJ, Boren J. Effects of liraglutide on the metabolism of triglyceride-rich lipoproteins in type 2 diabetes. Diabetes Obes Metab. 2021 May;23(5):1191-1201. doi: 10.1111/dom.14328. Epub 2021 Mar 5.
PubMed 33502078
Bjornson E, Packard CJ, Adiels M, Andersson L, Matikainen N, Soderlund S, Kahri J, Sihlbom C, Thorsell A, Zhou H, Taskinen MR, Boren J. Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics. J Intern Med. 2019 May;285(5):562-577. doi: 10.1111/joim.12877. Epub 2019 Mar 12.
PubMed 30779243

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 12 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02765399
Acronym / sponsor ID: LIRA
Conditions: Type 2 Diabetes
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 23 participants (actual)
Lead sponsor: Helsinki University Central HospitalUniversity, hospital or other
Collaborators: Göteborg University
Study start: 1 Feb 2015 (actual)
Primary completion: 28 Feb 2019 (actual)
Study completion: 28 Feb 2019 (actual)
First posted: 6 May 2016 (estimated)
Results: Posted 12 Apr 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 2

Arm	Type	Receives
Liraglutide	Experimental	Drug: LiraglutideLiraglutide 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.
Placebo	Placebo comparator	Drug: PlaceboPlacebo 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.

Who may qualify

Ages: 30 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (14 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LiraglutideAlso: Victoza	Drug	Liraglutide
Placebo	Drug	Placebo

Primary outcome

Change in Liver Fat Content
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.

11 secondary outcomes

Change in Hepatic de Novo Lipogenesis
Time frame: Baseline and after 16 weeks
Change in Systolic RR
Time frame: Baseline and after 16 weeks
Mean Total Production of apoB48
Time frame: Baseline and after 16 weeks
Mean Production Rate of apoB48 in CM
Time frame: Baseline and after 16 weeks
Mean apoB48 FTR to VLDL1 Particles
Time frame: Baseline and after 16 weeks
Mean TG Fractional Catabolic Rates in CM
Time frame: Baseline and after 16 weeks
Mean CM FDC of apoB48
Time frame: Baseline and after 16 weeks
Change in Direct CM-apoB48 Clearance
Time frame: Baseline and after 16 weeks
Mean CM-apoB48 Transfer Rates to VLDL1
Time frame: Baseline and after 16 weeks
Mean VLDL1-TG Production Rates
Time frame: Baseline and after16 weeks
Mean Fractional Catabolic Rate of VLDL2-apoB100
Time frame: Baseline and after 16 weeks

Results and safety

Results posted to the registry on 12 Apr 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Liraglutide	16	15
Placebo	7	7

Primary outcome: Change in Liver Fat Content

Time frame: Baseline and after 16 weeks. Mean (Standard Deviation). Unit: fat %

Measure	Liraglutide n = 15	Placebo n = 7
Baseline	14.8 (7.4)	16.1 (9.3)
16 weeks	10.7 (6.3)	13.9 (9.7)

Liraglutide: p = 0.001, Wilcoxon (Mann-Whitney)
Placebo: p = 0.028, Wilcoxon (Mann-Whitney)

Primary outcome: Plasma Triglyceride (TG) Area Under Curve (AUC)

Time frame: Baseline and after 16 weeks. Mean (Standard Deviation). Unit: mmol/l per h

Measure	Liraglutide n = 15	Placebo n = 7
Baseline	22.0 (7.4)	17.5 (4.8)
16 weeks	17.1 (5.0)	19.0 (6.2)

Liraglutide: p = 0.011, Wilcoxon (Mann-Whitney)
Placebo: p = 0.612, Wilcoxon (Mann-Whitney)

Primary outcome: Body Weight

Time frame: Baseline and after 16 weeks. Mean (Standard Deviation). Unit: kg

Measure	Liraglutide n = 15	Placebo n = 7
Baseline	98.6 (11.0)	92.0 (7.4)
16 weeks	96.1 (11.2)	89.8 (6.3)

Liraglutide: p = 0.002, Wilcoxon (Mann-Whitney)
Placebo: p = 0.128, Wilcoxon (Mann-Whitney)

Primary outcome: Change in HbA1c Level

Time frame: Baseline and after 16 weeks. Mean (Standard Deviation). Unit: HbA1c %

Measure	Liraglutide n = 15	Placebo n = 7
Baseline	7.0 (1.0)	6.3 (0.3)
16 weeks	6.4 (0.7)	6.4 (0.5)

Liraglutide: p = 0.005, Wilcoxon (Mann-Whitney)
Placebo: p = 0.343, Wilcoxon (Mann-Whitney)

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: During 16 weeks of Liraglutide therapy. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Liraglutide	0 of 16 (0%)	4 of 16 (25%)	0 of 16
Placebo	0 of 7 (0%)	1 of 7 (14.3%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 221537Zech 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. doi: 10.1172/JCI109421.
Background: PubMed 10480510Matsuda 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. doi: 10.2337/diacare.22.9.1462.
Background: PubMed 12730556Kernan 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. doi: 10.1161/01.STR.0000071108.00234.0E. Epub 2003 May 1.
Results publication: PubMed 30073766Matikainen N, Soderlund S, Bjornson E, Pietilainen K, Hakkarainen A, Lundbom N, Taskinen MR, Boren J. Liraglutide treatment improves postprandial lipid metabolism and cardiometabolic risk factors in humans with adequately controlled type 2 diabetes: A single-centre randomized controlled study. Diabetes Obes Metab. 2019 Jan;21(1):84-94. doi: 10.1111/dom.13487. Epub 2018 Sep 4.
Results publication: PubMed 33502078Taskinen MR, Bjornson E, Matikainen N, Soderlund S, Pietilainen KH, Ainola M, Hakkarainen A, Lundbom N, Fuchs J, Thorsell A, Andersson L, Adiels M, Packard CJ, Boren J. Effects of liraglutide on the metabolism of triglyceride-rich lipoproteins in type 2 diabetes. Diabetes Obes Metab. 2021 May;23(5):1191-1201. doi: 10.1111/dom.14328. Epub 2021 Mar 5.
Results publication: PubMed 30779243Bjornson E, Packard CJ, Adiels M, Andersson L, Matikainen N, Soderlund S, Kahri J, Sihlbom C, Thorsell A, Zhou H, Taskinen MR, Boren J. Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics. J Intern Med. 2019 May;285(5):562-577. doi: 10.1111/joim.12877. Epub 2019 Mar 12.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Niina Matikainen, MD, PhD principal investigator

Senior Endocrinologist

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Liraglutide in people with Type 2 Diabetes, run by Helsinki University Central Hospital at 1 site in Finland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Liver Fat Content (time frame: Baseline and after 16 weeks). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02765399, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2022.