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

NCT02765399 | Completed Phase 4 Results

• 1 other identifier: LIRA
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (10)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Baseline and after 16 weeks

Secondary Outcomes (11)

• Change in Hepatic de Novo Lipogenesis

  Baseline and after 16 weeks

• Change in Systolic RR

  Baseline and after 16 weeks

• Mean Total Production of apoB48

  Baseline and after 16 weeks

• Mean Production Rate of apoB48 in CM

  Baseline and after 16 weeks

• Mean apoB48 FTR to VLDL1 Particles

  Baseline and after 16 weeks

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

Liraglutide DRUG

Also known as: Victoza

Liraglutide

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Helsinki University Central Hospital: lead
• Göteborg University: collaborator

Study Sites (1)

Helsinki University Central Hospital

Helsinki, 00029, Finland

Location

Related Publications (6)

• 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.

  PMID: 221537 BACKGROUND

• 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.

  PMID: 10480510 BACKGROUND

• 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.

  PMID: 12730556 BACKGROUND

• 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.

  PMID: 30073766 RESULT

• 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.

  PMID: 33502078 RESULT

• 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.

  PMID: 30779243 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Prof. Marja-Riitta Taskinen
• Organization: Helsinki University and Helsinki University Hospital

marja-riitta.taskinen@helsinki.fi

+358-9-47171990

Study Officials

• Niina Matikainen, MD, PhD

  Senior Endocrinologist

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Endocrinologist

Study Record Dates

• First Submitted: May 2, 2016
• First Posted: May 6, 2016
• Study Start: February 1, 2015
• Primary Completion: February 28, 2019
• Study Completion: February 28, 2019
• Last Updated: April 12, 2022
• Results First Posted: April 12, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)