The Effect of Oral Semaglutide on Bone Turnover in Patients With T2D: a Randomized Placebo-controlled Clinical Trial

Phase 2

Recruiting

• Conditions: Type 2 Diabetes; Osteopenia
• Interventions: Drug: oral Semaglutide/Rybelsus; Drug: Placebo

• Registration Number: NCT06050577
• Lead Sponsor: Odense University Hospital

Brief Summary

The hypothesis for this study is that oral Semaglutide, a GLP-1Ra, has a positive effect on the balance between build-up and degradation as well as the strength of the bones in men and women aged 50-85 years with type 2 diabetes and an increased risk of bone fractures. Treatment involves once daily oral GLP-1Ra semaglutide or matching placebo for 52 weeks. The effect will be measured by bone markers in blood samples, bone scans, bone tissue and bone marrow tests (bone marrow aspiration and biopsy), physical activity assessed by a questionnaire, and direct bone strength measured by microindentation at the start and end of the study.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-08
• Study First Submitted QC: 2023-09-21
• Study First Posted: 2023-09-22
• Study Start: 2024-06-07
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-30
• Primary Completion: 2025-11
• Study Completion: 2025-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
oral Semaglutide/Rybelsus	oral Semaglutide/Rybelsus	oral Semaglutide 7-14 mg (or highest tolerated dose) once daily for 52 weeks (incl. titration)
oral Placebo	Placebo	oral Placebo 7-14 mg (or highest tolerated dose) once daily for 52 weeks (incl. titration)

Primary Outcome Measures

Name	Time	Method
Procollagen type 1 N-terminal propeptide (P1NP)	Baseline and 52 weeks	Percentage changes in bone formation marker P1NP from baseline and after 12 months

Secondary Outcome Measures

Name	Time	Method
Collagen 1 cross link C-terminal telopeptide (CTX)	Baseline and 52 weeks	Changes in bone resorption marker CTX from baseline and after 12 months
Osteocalcin	Baseline and 52 weeks	Changes in bone formation marker osteocalcin from baseline and after 12 months
Bone specific alkaline phosphatase (BALP)	Baseline and 52 weeks	Changes in bone formation marker BALP from baseline and after 12 months
Bone mineral density (BMD)	Baseline and 52 weeks	Changes in BMD (total hip, femoral neck and lumbar spine (L1-4)) assessed by DXA scans from baseline and after 12 months
Estimated bone strength	Baseline and 52 weeks	Changes in estimated bone strength assessed by finite elemental analysis (HR-pQCT scan) from baseline and after 12 months
Cortical porosity	Baseline and 52 weeks	Changes in cortical porosity assessed by HR-pQCT scan of tibia and radius
Bone formation rate	52 weeks	Changes in bone formation rate (BRF/BS, µm\^3/µm\^2 per day), the volume of mineralized bone made per unit surface of bone per year, based on dynamic histomorphometry of bone tissue
Lean tissue distribution	Baseline and 52 weeks	Change in lean tissue distribution, assessed by DXA
Glycosylated haemoglobin (HbA1C)	Baseline and 52 weeks	Change in HbA1c from baseline and after 12 months
Physical activity	Baseline and 52 weeks	Change in physical activity based on analysis of International Physical Activity Questionnaire Short Form (IPAQ-SF) from baseline and after 12 months
Total volumetric BMD	Baseline and 52 weeks	Changes in total volumetric BMD (mg/cm\^3) assessed by HR-pQCT scan of distal tibia and radius
Trabecular thickness	Baseline and 52 weeks	Changes in trabecular thickness (mm) assessed by HR-pQCT scan of distal tibia and radius
Cortical thickness	Baseline and 52 weeks	Changes in cortical thickness (mm) assessed by HR-pQCT scan of distal tibia and radius
Trabecular volumetric BMD	Baseline and 52 weeks	Changes in trabecular volumetric BMD (mg/cm\^3) assessed by HR-pQCT scan of distal tibia and radius
Cortical volumetric BMD	Baseline and 52 weeks	Changes in cortical volumetric BMD (mg/cm\^3) assessed by HR-pQCT scan of distal tibia and radius
Bone volume	Baseline and 52 weeks	Changes in trabecular bone volume pr total volume (BV/TV) assessed by HR-pQCT scan of distal tibia and radius
Fat tissue distribution	Baseline and 52 weeks	Change in fat tissue distribution, assessed by DXA
Body mass index (BMI)	Baseline and 52 weeks	Change in BMI from baseline and after 12 months

Trial Locations

Locations (1)

Odense University Hospital; 🇩🇰 Odense, Denmark