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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Diabetes Complications, Osteoporosis

Intervention / Treatment
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* Drug: Liraglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide<br>Liraglutide (Victoza), subcutaneous 1,8 mg once daily for 180 days | Drug: Liraglutide<br>* Once daily<br>* Other names: Victoza;|
| Placebo Comparator: Placebo<br>Saline, subcutaneous once daily for 180 days | Drug: Placebo<br>* Once daily<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Change in procollagen type I N-terminal propeptide measured in serum |  | Days 0, 7, 28, 90, 180 |