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

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06050577
• Other study ID #: EU CT: 2023-505959-45-00
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: October 2023
• Est. completion date: November 2025

Study information

• Verified date: September 2023
• Source: Odense University Hospital
• Contact: Julie Bjerrelund, MD
• Phone: +4529849154
• Email: julie.bjerrelund[@]rsyd.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 64
• Est. completion date: November 2025
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Bone Diseases, Metabolic
• Diabetes Mellitus, Type 2
• Osteopenia
• Type 2 Diabetes

Intervention

Drug:
• oral Semaglutide/Rybelsus
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
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.

Locations

Country	Name	City	State
Denmark	Odense University Hospital	Odense

Sponsors (1)

Lead Sponsor	Collaborator
Odense University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Osteogenic potential	Change in osteogenic potential, i.e., ability to form new bone, assessed using spatial transcriptomics and single-cell RNA sequencing.	52 weeks
Primary	Procollagen type 1 N-terminal propeptide (P1NP)	Percentage changes in bone formation marker P1NP from baseline and after 12 months	Baseline and 52 weeks
Secondary	Collagen 1 cross link C-terminal telopeptide (CTX)	Changes in bone resorption marker CTX from baseline and after 12 months	Baseline and 52 weeks
Secondary	Osteocalcin	Changes in bone formation marker osteocalcin from baseline and after 12 months	Baseline and 52 weeks
Secondary	Bone specific alkaline phosphatase (BALP)	Changes in bone formation marker BALP from baseline and after 12 months	Baseline and 52 weeks
Secondary	BMSi	Changes in direct bone strength measured by microindentation from baseline and after 12 months	Baseline and 52 weeks
Secondary	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	Baseline and 52 weeks
Secondary	Estimated bone strength	Changes in estimated bone strength assessed by finite elemental analysis (HR-pQCT scan) from baseline and after 12 months	Baseline and 52 weeks
Secondary	Total volumetric BMD	Changes in total volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius	Baseline and 52 weeks
Secondary	Trabecular volumetric BMD	Changes in trabecular volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius	Baseline and 52 weeks
Secondary	Cortical volumetric BMD	Changes in cortical volumetric BMD (mg/cm^3) assessed by HR-pQCT scan of distal tibia and radius	Baseline and 52 weeks
Secondary	Bone volume	Changes in trabecular bone volume pr total volume (BV/TV) assessed by HR-pQCT scan of distal tibia and radius	Baseline and 52 weeks
Secondary	Trabecular thickness	Changes in trabecular thickness (mm) assessed by HR-pQCT scan of distal tibia and radius	Baseline and 52 weeks
Secondary	Cortical thickness	Changes in cortical thickness (mm) assessed by HR-pQCT scan of distal tibia and radius	Baseline and 52 weeks
Secondary	Cortical porosity	Changes in cortical porosity assessed by HR-pQCT scan of tibia and radius	Baseline and 52 weeks
Secondary	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	52 weeks
Secondary	Fat tissue distribution	Change in fat tissue distribution, assessed by DXA	Baseline and 52 weeks
Secondary	Lean tissue distribution	Change in lean tissue distribution, assessed by DXA	Baseline and 52 weeks
Secondary	Glycosylated haemoglobin (HbA1C)	Change in HbA1c from baseline and after 12 months	Baseline and 52 weeks
Secondary	Physical activity	Change in physical activity based on analysis of International Physical Activity Questionnaire Short Form (IPAQ-SF) from baseline and after 12 months	Baseline and 52 weeks
Secondary	Body mass index (BMI)	Change in BMI from baseline and after 12 months	Baseline and 52 weeks