Short summary

This is a single-centre, randomised, placebo-controlled clinical trial that investigates the effects of the glucagon-like peptide 1 analogue exenatide on bone metabolism in post-menopausal women.

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Rationale

Glucagon-like peptide 1-receptor agonists (GLP-1-Ra) are commonly used for the treatment of type 2 diabetes because these drugs increase glucose-dependent insulin secretion. The GLP-1 receptor is expressed in osteoblasts. Bone mass is reduced in GLP-1 knockout mice, and exendin-4, a GLP-1 receptor agonists, promotes bone formation and impairs bone resorption in mice. The effects of GLP-1 receptor agonists on bone metabolism in humans remain to be investigated.

The aim of this investigation is, in a single-centre, randomized, placebo-controlled clinical trial, to investigate the effects of twelve weeks of once weekly subcutaneous injection of 2 mgs of exenatide on the bone formation marker procollagen I, N-terminal pro-peptide (P1NP) in post-menopausal women. As secondary outcomes, changes in levels of markers of bone resorption, bone histomorphometry assessed by high-resolution peripheral quantitative CT scan (HR-pQCT) and histomorphometry are considered.

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Description of the cohort

This study is to comprise 66 post-menopausal women. Prevalent diseases including any form of diabetes mellitus, use of anti-diabetic medications within the last three months, abnormalities in calcium metabolism, use of anti-resorptive or bone anabolic drugs within the last 12 months, fractures within the last six months, renal disease, hormone (eGFR < 50 ml/min), replacement therapy, diseases associated with development of osteoporosis (untreated thyrotoxicosis, rheumatoid arthritis, pituitary failure, severe COPD, reduced liver function), current use of anti-epileptic drugs or aromatase inhibitors, any history of pancreatitis, increased levels of triglycerides, allergy towards exenatide, daily intake of more than six units of alcohol, use of herbal medication and inability to provide informed consent are considered exclusion criteria.

Participants are recruited from the general population using advertisements.

Data and biological material

Bone turnover markers are measured in serum obtained from peripheral blood. Bone histomorphometry is performed on nine mm transiliac bone biopsies after tetracycline labelling. HR-pQCT is used to assess bone geometry, microarchitecture and strength.