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NCT Number: NCT06050577

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

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.

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Key information

Conditions

Type 2 Diabetes Bone Diseases Bone Diseases, Metabolic Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Musculoskeletal Diseases Nutritional and Metabolic Diseases Osteopenia

Age range

50 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Odense University Hospital

Odense, 5000, Denmark

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Type 2 diabetes and glycosylated haemoglobin (HbA1C) of 48-91 mmol/mol (6.5-10.5%) and
  • T-score <-1 in hip or lower back, assessed by DXA scan and / or
  • Low-energy fracture within the last 3 years

Exclusion criteria

  • T-score <-2.5 in hip or lower back, assessed by DXA scan, although these individuals may be included if they are not candidates for conventional osteoporosis therapy, e.g., due to allergies and renal impairment, or if they prefer to participate in the trial.
  • Type 1 diabetes mellitus
  • Severe NPDR (non-proliferative diabetic retinopathy) or PDR (proliferative diabetic retinopathy) assessed within the last year. If a recent assessment is unavailable, a new retinal photo test will be performed.
  • Congestive heart failure (NYHA Class IV)
  • Primary hyperparathyroidism
  • Vitamin D deficiency (<25 nM) (re-test after substitution acceptable)
  • Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, severe renal impairment (eGFR <30) or liver dysfunction (baseline phosphatase higher than twice upper limit (105 U/L)), rheumatism, celiac disease, hypogonadism, severe COPD, hypopituitarism, Cushing's disease
  • Clinically significant concomitant diseases or disorders (e.g., cancer) or clinically significant abnormal values in laboratory screening tests, including increased Choriogonadotropin (hCG) in women.
  • History of gastrointestinal surgery (except uncomplicated surgical procedures such as hernia surgery and appendectomy)
  • Antiresorptive or bone anabolic drugs for the last 12 months
  • Use of anabolic steroids in the previous year
  • Use of GLP-1Ras within 90 days
  • Stable therapy with DPP4 inhibitors (unless the patient is willing to discontinue the treatment)
  • History of pancreatitis
  • Allergy or hypersensitivity to the active substance or to any of the ingredients
  • Inability to give informed consent
  • Previous bariatric surgery
  • BMI <20 kg/m2 or BMI>37 kg/m2

Treatment and study plan

oral Semaglutide/Rybelsus

Drug

Weeks 1-4: 3 mg of oral semaglutide once daily. Weeks 5-52: 7 mg of semaglutide once daily as maintenance dose. Dose may be increased to 14 mg of semaglutide once daily as maintenance dose after 2 months if glucose levels are out of range.

Placebo

Drug

Weeks 1-4: 3 mg of oral placebo once daily. Weeks 5-52: 7 mg of placebo once daily as maintenance dose. Dose may be increased to 14 mg of placebo once daily as maintenance dose after 2 months if glucose levels are out of range.

Primary outcomes

  1. Procollagen type 1 N-terminal propeptide (P1NP)

    Time frame: Baseline and 52 weeks

    Percentage changes in bone formation marker P1NP from baseline and after 12 months

Secondary outcomes

  1. Collagen 1 cross link C-terminal telopeptide (CTX)

    Time frame: Baseline and 52 weeks

    Changes in bone resorption marker CTX from baseline and after 12 months

  2. Osteocalcin

    Time frame: Baseline and 52 weeks

    Changes in bone formation marker osteocalcin from baseline and after 12 months

  3. Bone specific alkaline phosphatase (BALP)

    Time frame: Baseline and 52 weeks

    Changes in bone formation marker BALP from baseline and after 12 months

  4. Bone mineral density (BMD)

    Time frame: 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

  5. Estimated bone strength

    Time frame: Baseline and 52 weeks

    Changes in estimated bone strength assessed by finite elemental analysis (HR-pQCT scan) from baseline and after 12 months

  6. Total volumetric BMD

    Time frame: Baseline and 52 weeks

    Changes in total volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius

  7. Trabecular volumetric BMD

    Time frame: Baseline and 52 weeks

    Changes in trabecular volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius

  8. Cortical volumetric BMD

    Time frame: Baseline and 52 weeks

    Changes in cortical volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius

  9. Bone volume

    Time frame: Baseline and 52 weeks

    Changes in trabecular bone volume pr total volume (BV/TV) assessed by HR-pQCT scan of distal tibia and radius

  10. Trabecular thickness

    Time frame: Baseline and 52 weeks

    Changes in trabecular thickness (mm) assessed by HR-pQCT scan of distal tibia and radius

  11. Cortical thickness

    Time frame: Baseline and 52 weeks

    Changes in cortical thickness (mm) assessed by HR-pQCT scan of distal tibia and radius

  12. Cortical porosity

    Time frame: Baseline and 52 weeks

    Changes in cortical porosity assessed by HR-pQCT scan of tibia and radius

  13. Bone formation rate

    Time frame: 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

  14. Fat tissue distribution

    Time frame: Baseline and 52 weeks

    Change in fat tissue distribution, assessed by DXA

  15. Lean tissue distribution

    Time frame: Baseline and 52 weeks

    Change in lean tissue distribution, assessed by DXA

  16. Glycosylated haemoglobin (HbA1C)

    Time frame: Baseline and 52 weeks

    Change in HbA1c from baseline and after 12 months

  17. Physical activity

    Time frame: 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

  18. Body mass index (BMI)

    Time frame: Baseline and 52 weeks

    Change in BMI from baseline and after 12 months

Other outcomes

  1. Osteogenic potential

    Time frame: 52 weeks

    Change in osteogenic potential, i.e., ability to form new bone, assessed using spatial transcriptomics and single-cell RNA sequencing.

Sponsors and collaborators

Lead sponsor

Odense University Hospital

Other

Registry information

Official study title

The Effect of Oral Semaglutide on Bone Turnover in Patients With Type 2 Diabetes: a Randomized Placebo-controlled Clinical Trial - (SOBER II)

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
Sep 22, 2023
Registry last updated
Feb 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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