Type 2 DiabetesPhase 2NCT06050577
The Effect of Oral Semaglutide on Bone Turnover in Patients With T2D: a Randomized Placebo-controlled Clinical Trial
A Phase 2 study testing oral Semaglutide/Rybelsus in people with Type 2 Diabetes and Osteopenia, run by Odense University Hospital at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Type 2 Diabetes, Osteopenia
- What is being tested?
- oral Semaglutide/Rybelsus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteDenmark
- Study dates
- 7 Jun 2024to 15 Mar 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Oral Semaglutide on Bone Turnover in Patients With Type 2 Diabetes: a Randomized Placebo-controlled Clinical Trial - (SOBER II)
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.
- Conditions
- Type 2 Diabetes, Osteopenia
- Being tested
- oral Semaglutide/Rybelsus, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 2, Bone Diseases, Metabolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oral Semaglutide/RybelsusDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| oral Semaglutide/Rybelsus | Experimental | oral Semaglutide 7-14 mg (or highest tolerated dose) once daily for 52 weeks (incl. titration) Receives: Drug: oral Semaglutide/Rybelsus |
| oral Placebo | Placebo comparator | oral Placebo 7-14 mg (or highest tolerated dose) once daily for 52 weeks (incl. titration) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Procollagen type 1 N-terminal propeptide (P1NP)
Percentage changes in bone formation marker P1NP from baseline and after 12 months
Measured: Baseline and 52 weeks
Secondary outcomes (18)
Collagen 1 cross link C-terminal telopeptide (CTX)
Changes in bone resorption marker CTX from baseline and after 12 months
Measured: Baseline and 52 weeks
Osteocalcin
Changes in bone formation marker osteocalcin from baseline and after 12 months
Measured: Baseline and 52 weeks
Bone specific alkaline phosphatase (BALP)
Changes in bone formation marker BALP from baseline and after 12 months
Measured: Baseline and 52 weeks
Bone mineral density (BMD)
Changes in BMD (total hip, femoral neck and lumbar spine (L1-4)) assessed by DXA scans from baseline and after 12 months
Measured: Baseline and 52 weeks
Estimated bone strength
Changes in estimated bone strength assessed by finite elemental analysis (HR-pQCT scan) from baseline and after 12 months
Measured: Baseline and 52 weeks
Total volumetric BMD
Changes in total volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius
Measured: Baseline and 52 weeks
Trabecular volumetric BMD
Changes in trabecular volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius
Measured: Baseline and 52 weeks
Cortical volumetric BMD
Changes in cortical volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius
Measured: Baseline and 52 weeks
Bone volume
Changes in trabecular bone volume pr total volume (BV/TV) assessed by HR-pQCT scan of distal tibia and radius
Measured: Baseline and 52 weeks
Trabecular thickness
Changes in trabecular thickness (mm) assessed by HR-pQCT scan of distal tibia and radius
Measured: Baseline and 52 weeks
Cortical thickness
Changes in cortical thickness (mm) assessed by HR-pQCT scan of distal tibia and radius
Measured: Baseline and 52 weeks
Cortical porosity
Changes in cortical porosity assessed by HR-pQCT scan of tibia and radius
Measured: Baseline and 52 weeks
Bone formation rate
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
Measured: 52 weeks
Fat tissue distribution
Change in fat tissue distribution, assessed by DXA
Measured: Baseline and 52 weeks
Lean tissue distribution
Change in lean tissue distribution, assessed by DXA
Measured: Baseline and 52 weeks
Glycosylated haemoglobin (HbA1C)
Change in HbA1c from baseline and after 12 months
Measured: Baseline and 52 weeks
Physical activity
Change in physical activity based on analysis of International Physical Activity Questionnaire Short Form (IPAQ-SF) from baseline and after 12 months
Measured: Baseline and 52 weeks
Body mass index (BMI)
Change in BMI from baseline and after 12 months
Measured: Baseline and 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2023
- Study start7 Jun 2024
- Primary completion15 Jan 2027 (estimated)
- Study completion15 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Odense University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06050577
- Sponsor's protocol ID
- EU CT: 2023-505959-45-00
- Status last verified
- Oct 2026
- First submitted
- 8 Sep 2023
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No