Effect of GLP-1 Receptor Agonists on Trabecular Bone Score

Study Overview
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Brief Summary
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This study will help determine the effect of Glucagon Like Peptide-1 (GLP-1)receptor agonists on bone strength in postmenopausal women with type 2 diabetes mellitus (T2DM)

Detailed Description
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Postmenopausal women with diabetes mellitus have a higher risk of osteoporotic fractures, with significant associated mortality and morbidity. Osteoporosis is underdiagnosed in diabetes, as the bone mineral density (BMD) as currently measured is often normal despite underlying abnormalities. The trabecular bone score (TBS) is a novel modality to assess bone microarchitecture and accurately assess fracture risk in patients with diabetes. Due to increased co-prevalence of osteoporosis and diabetes mellitus, the potential effects of antidiabetic medications on fracture risk assume importance. Based on findings in animal studies, we hypothesize that GLP-1 receptor agonists increase TBS in postmenopausal women with (T2DM). The investigators propose a prospective non-randomized study by enrolling 48 patients (24 in the GLP-1 group and 24 in the non-GLP group). Dual-energy X-ray Absorptiometry (DXA )scans, markers of bone formation, and resorption, and selected inflammatory markers will be assessed at baseline, six months, and one year.

Official Title
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Effect of GLP-1 Receptor Agonists on Trabecular Bone Score and Visceral Adiposity in Postmenopausal Women With Type 2 Diabetes Mellitus.

Conditions
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Osteoporosis, Postmenopausal, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: GLP-1 receptor agonist


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Type 2 Diabetes Mellitus Postmenopausal female Age >55 years Hemoglobin A1c between 7-10% within 6 months of the first visit. Exclusion Criteria: Patients with type 1 Diabetes mellitus Patients with a history of GLP-1 receptor agonist/DPP4 inhibitor use eGFR <30 ml/min in the last 3 months Patients with a history of pancreatitis Personal or family history of medullary thyroid cancer Patients with a history of treatment with anti-osteoporosis agents Documented secondary osteoporosis Documented presence of prosthesis or devices in the spine Unwilling or unable to consent

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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Female

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLP-1 cohort<br>Participants on GLP-1 receptor agonists | Drug: GLP-1 receptor agonist<br>* Diabetes medication<br>|
| No Intervention: Non GLP-1 cohort<br>Participants not on GLP-1 receptor agonists | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trabecular bone score | The change in TBS from baseline to six months and one year after the initiation of a GLP-1 receptor agonist. TBS will be assessed by DXA scans done at baseline, six months and one year. | 12 months after index date | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory markers and Bone resorption markers | The change in inflammatory markers (IL-1, IL-6 and TNF-alpha) and bone resorption markers (C-telopeptide) at 6 and 12 months after starting GLP-1 receptor agonists as compared to baseline. | 12 months after index date | 
| Visceral fat mass | The change in visceral fat mass (measured by DXA) at 6 and 1 year after starting GLP-1 receptor agonists as compared to baseline. | 12 months after index date | 
| Sclerostin and Bone formation markers | The change in levels of sclerostin, osteocalcin, and P1NP (as measured by commercial assays) from baseline to six months and one year after starting GLP-1 receptor agonist. | 12 months after index date |