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

NCT06050577 | Active Not Recruiting Phase 2

• 1 other identifier: EU CT: 2023-505959-45-00
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes; Osteopenia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (18)

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

  Baseline and 52 weeks

• Osteocalcin

  Baseline and 52 weeks

• Bone specific alkaline phosphatase (BALP)

  Baseline and 52 weeks

• Bone mineral density (BMD)

  Baseline and 52 weeks

• Estimated bone strength

  Baseline and 52 weeks

Other Outcomes (1)

• Osteogenic potential

  52 weeks

Study Arms (2)

oral Semaglutide/Rybelsus

EXPERIMENTAL

oral Semaglutide 7-14 mg (or highest tolerated dose) once daily for 52 weeks (incl. titration)

Drug: oral Semaglutide/Rybelsus

oral Placebo

PLACEBO COMPARATOR

oral Placebo 7-14 mg (or highest tolerated dose) once daily for 52 weeks (incl. titration)

Drug: Placebo

Interventions

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.

oral Semaglutide/Rybelsus

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.

oral Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Odense University Hospital: lead

Study Sites (1)

Odense University Hospital

Odense, 5000, Denmark

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Bone Diseases, Metabolic

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Bone Diseases; Musculoskeletal Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2023
• First Posted: September 22, 2023
• Study Start: June 7, 2024
• Primary Completion: January 15, 2026
• Study Completion (Estimated): January 15, 2027
• Last Updated: February 9, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)