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

Osteoporosis Clinical Trial

— LIRABONE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02473809
• Other study ID #: 07052015
• Status: Completed
• Phase: Phase 4
• Start date: August 2015
• Est. completion date: October 2017

Study information

• Verified date: September 2018
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Background: Type 2 diabetes may cause complications such as ischemic heart disease, nephropathy, neuropathy, and retinopathy. Several epidemiologic and animal studies also suggest that fracture risk is increased in diabetes.

Bone is remodelled throughout life through bone resorption by the bone resorbing cells, the osteoclasts, and by bone formation by the bone forming cells, the osteoblasts. Bone remodelling can be monitored by biochemical markers of bone turnover and the effect of bone remodelling can be measured by changes in bone mineral density (BMD) by Dual X-ray absorptiometry (DXA) or bone structure by quantitative CT (QCT) or high resolution peripheral QCT (HRpQCT). The remodelling activity and the balance between resorption and formation are influenced by many factors including food consumption. The gut hormone glucagon-like polypeptide 1 (GLP-1) is released in relation to food intake and reduces serum levels of glucagon, increases serum levels of insulin, and reduces blood glucose in diabetes. Liraglutide is a GLP-1 analogue and has been approved for the treatment of type 2 diabetes.

Aim: To investigate the effect of the GLP-1 analogue Liraglutide on bone turnover, bone mass, and bone structure in patients with type 2 diabetes.

Methods: The clinical study will be conducted as a randomised, double-blinded, placebo-controlled, prospective, clinical trial with comparative treatment regimes with either subcutaneous Liraglutide or subcutaneous placebo injections.

Perspectives: The project will bring new knowledge about the possible effects of GLP-1 analogues on bone turnover and structure. This is important given that type 2 diabetes deteriorates bone health and increases 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: October 2017
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 90 Years

Eligibility

Inclusion Criteria:

• Informed consent

• Diagnosis of type 2 diabetes (HbA1c > 48 mmol/mol)

• Age older than 30 years

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Diabetes Complications
• Osteoporosis

Intervention

Drug:
• Liraglutide
Once daily
• Placebo
Once daily

Locations

Country	Name	City	State
Denmark	Department of Endocrinology and Internal Medicine, Aarhus University Hospital	Aarhus	Aarhus C

Sponsors (3)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital, Novo Nordisk A/S

Country where clinical trial is conducted

Denmark, 

References & Publications (7)

Fehmann HC, Hering BJ, Wolf MJ, Brandhorst H, Brandhorst D, Bretzel RG, Federlin K, Göke 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. — View Citation

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. Review. — View Citation

Nuche-Berenguer B, Lozano D, Gutiérrez-Rojas I, Moreno P, Mariñoso ML, Esbrit P, Villanueva-Peñacarrillo 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. — View Citation

Schwartz AV, Sellmeyer DE. Diabetes, fracture, and bone fragility. Curr Osteoporos Rep. 2007 Sep;5(3):105-11. Review. — View Citation

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. Review. — View Citation

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. Epub 2006 Oct 27. Review. — View Citation

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. Epub 2007 Nov 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in bone alkaline phosphatase measured in serum		Days 0, 7, 28, 90, 180
Secondary	Change in BMD evaluated by DXA		Days 0, 90, 180
Secondary	Change in bone structure evaluated by QCT and HRpQCT		Days 0, 90, 180
Secondary	Change in HbA1c		Days 0, 180
Secondary	Change in osteocalcin measured in serum		Days 0, 7, 28, 90, 180
Secondary	Change in procollagen type I N-terminal propeptide measured in serum		Days 0, 7, 28, 90, 180