The Effect of Liraglutide on Bone Turnover, Bone Mass and Bone Cell Function

NCT02473809 | Completed Phase 4 DMC

• 1 other identifier: 07052015
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test whether liraglutide, a drug approved and widely used in the treatment of type 2 diabetes, has an effect on bone mass and bone cell function. Type 2 diabetes may cause multiple complications, and it is well known that patients with type 2 diabetes have a higher risk of fractures. If Liraglutide can be demonstrated to have a positive effect on bone, this may be one among other factors to consider before the decision about specific treatment of type 2 diabetes is made for the individual patient.

Conditions

Diabetes Complications; Osteoporosis

Outcome Measures

Primary Outcomes (1)

• Change in collagen I cross-linked C-terminal telopeptide measured in serum

  Collagen I cross-linked C-terminal telopeptide has been chosen as primary endpoint as the expected mechanism of action is reduction in bone resorption, and as it is the most responsive bone resorption marker.

  Days 0, 7, 28, 90, 180

Secondary Outcomes (6)

• Change in bone alkaline phosphatase measured in serum

  Days 0, 7, 28, 90, 180

• Change in BMD evaluated by DXA

  Days 0, 90, 180

• Change in bone structure evaluated by QCT and HRpQCT

  Days 0, 90, 180

• Change in HbA1c

  Days 0, 180

• Change in osteocalcin measured in serum

  Days 0, 7, 28, 90, 180

Study Arms (2)

Liraglutide

EXPERIMENTAL

Liraglutide ("Victoza"), subcutaneous 1,8 mg once daily for 180 days

Drug: Liraglutide

Placebo

PLACEBO COMPARATOR

Saline, subcutaneous once daily for 180 days

Drug: Placebo

Interventions

Liraglutide DRUG

Once daily

Also known as: Victoza

Liraglutide

Placebo DRUG

Once daily

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 30 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent
• Diagnosis of type 2 diabetes (HbA1c \> 48 mmol/mol)
• Age older than 30 years

You may not qualify if:

• Type 1 diabetes
• Treatment with insulin
• Body weight \> 140 kg
• HbA1c \> 75 mmol/mol
• Treatment with GLP-1 analogues, Dipeptidyl peptidase-4 inhibitors, or glitazones
• Chronic kidney disease
• Hepatic disease
• Pancreatitis
• Inflammatory bowel disease
• Osteoporosis
• Family or personal history of medullary thyroid carcinoma
• Treatment with glucocorticoids
• Hormone replacement therapy
• Diabetic gastroparesis
• Pregnancy or lactation

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital: collaborator
• Novo Nordisk A/S: collaborator

Study Sites (1)

Department of Endocrinology and Internal Medicine, Aarhus University Hospital

Aarhus, Aarhus C, 8000, Denmark

Location

Related Publications (7)

• Fehmann HC, Hering BJ, Wolf MJ, Brandhorst H, Brandhorst D, Bretzel RG, Federlin K, Goke B. The effects of glucagon-like peptide-I (GLP-I) on hormone secretion from isolated human pancreatic islets. Pancreas. 1995 Aug;11(2):196-200. doi: 10.1097/00006676-199508000-00014.

  PMID: 7479679 BACKGROUND

• Leslie WD, Rubin MR, Schwartz AV, Kanis JA. Type 2 diabetes and bone. J Bone Miner Res. 2012 Nov;27(11):2231-7. doi: 10.1002/jbmr.1759. Epub 2012 Sep 28.

  PMID: 23023946 BACKGROUND

• Schwartz AV, Sellmeyer DE. Diabetes, fracture, and bone fragility. Curr Osteoporos Rep. 2007 Sep;5(3):105-11. doi: 10.1007/s11914-007-0025-x.

  PMID: 17925191 BACKGROUND

• Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes--a meta-analysis. Osteoporos Int. 2007 Apr;18(4):427-44. doi: 10.1007/s00198-006-0253-4. Epub 2006 Oct 27.

  PMID: 17068657 BACKGROUND

• Yamada C, Yamada Y, Tsukiyama K, Yamada K, Udagawa N, Takahashi N, Tanaka K, Drucker DJ, Seino Y, Inagaki N. The murine glucagon-like peptide-1 receptor is essential for control of bone resorption. Endocrinology. 2008 Feb;149(2):574-9. doi: 10.1210/en.2007-1292. Epub 2007 Nov 26.

  PMID: 18039776 BACKGROUND

• Nuche-Berenguer B, Lozano D, Gutierrez-Rojas I, Moreno P, Marinoso ML, Esbrit P, Villanueva-Penacarrillo ML. GLP-1 and exendin-4 can reverse hyperlipidic-related osteopenia. J Endocrinol. 2011 May;209(2):203-10. doi: 10.1530/JOE-11-0015. Epub 2011 Mar 3.

  PMID: 21372151 BACKGROUND

• Su B, Sheng H, Zhang M, Bu L, Yang P, Li L, Li F, Sheng C, Han Y, Qu S, Wang J. Risk of bone fractures associated with glucagon-like peptide-1 receptor agonists' treatment: a meta-analysis of randomized controlled trials. Endocrine. 2015 Feb;48(1):107-15. doi: 10.1007/s12020-014-0361-4. Epub 2014 Jul 30.

  PMID: 25074632 BACKGROUND

MeSH Terms

Conditions

Diabetes Complications; Osteoporosis

Interventions

Liraglutide; Sodium Chloride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Endocrine System Diseases; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Bente L Langdahl, MD PhD DMSc

  Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2015
• First Posted: June 17, 2015
• Study Start: August 1, 2015
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: September 26, 2018

Record last verified: 2018-09

Locations

DK (1)