Clinical trial NCT02473809: The Effect of Liraglutide on Bone Turnover, Bone Mass and Bone Cell Function
Official title: The Effect of Liraglutide on Bone Turnover, Bone Mass and Bone Cell Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Complications
Osteoporosis
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: Novo Nordisk A/S
First posted: 2015-06-17
Enrollment: 60
Sex: ALL
Minimum age (years): 30
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in collagen I cross-linked C-terminal telopeptide measured in serum
timeFrame: Days 0, 7, 28, 90, 180
Secondary outcomes:
measure: Change in bone alkaline phosphatase measured in serum
timeFrame: Days 0, 7, 28, 90, 180
measure: Change in BMD evaluated by DXA
timeFrame: Days 0, 90, 180
measure: Change in bone structure evaluated by QCT and HRpQCT
timeFrame: Days 0, 90, 180
measure: Change in HbA1c
timeFrame: Days 0, 180
measure: Change in osteocalcin measured in serum
timeFrame: Days 0, 7, 28, 90, 180
measure: Change in procollagen type I N-terminal propeptide measured in serum
timeFrame: Days 0, 7, 28, 90, 180
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Endocrinology and Internal Medicine, Aarhus University Hospital
state: Aarhus C
Study officials:
affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark
name: Bente L Langdahl, MD PhD DMSc
role: STUDY_DIRECTOR
References:
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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. doi: 10.1210/en.2007-1292. Epub 2007 Nov 26.
citation: 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.
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.