Clinical trial NCT06050577: The Effect of Oral Semaglutide on Bone Turnover in Patients With T2D: a Randomized Placebo-controlled 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Type 2 Diabetes
Osteopenia
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
First posted: 2023-09-22
Enrollment: 64
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Procollagen type 1 N-terminal propeptide (P1NP)
timeFrame: Baseline and 52 weeks
Secondary outcomes:
measure: Collagen 1 cross link C-terminal telopeptide (CTX)
timeFrame: Baseline and 52 weeks
measure: Osteocalcin
timeFrame: Baseline and 52 weeks
measure: Bone specific alkaline phosphatase (BALP)
timeFrame: Baseline and 52 weeks
measure: Bone mineral density (BMD)
timeFrame: Baseline and 52 weeks
measure: Estimated bone strength
timeFrame: Baseline and 52 weeks
measure: Total volumetric BMD
timeFrame: Baseline and 52 weeks
measure: Trabecular volumetric BMD
timeFrame: Baseline and 52 weeks
measure: Cortical volumetric BMD
timeFrame: Baseline and 52 weeks
measure: Bone volume
timeFrame: Baseline and 52 weeks
measure: Trabecular thickness
timeFrame: Baseline and 52 weeks
measure: Cortical thickness
timeFrame: Baseline and 52 weeks
measure: Cortical porosity
timeFrame: Baseline and 52 weeks
measure: Bone formation rate
timeFrame: 52 weeks
measure: Fat tissue distribution
timeFrame: Baseline and 52 weeks
measure: Lean tissue distribution
timeFrame: Baseline and 52 weeks
measure: Glycosylated haemoglobin (HbA1C)
timeFrame: Baseline and 52 weeks
measure: Physical activity
timeFrame: Baseline and 52 weeks
measure: Body mass index (BMI)
timeFrame: Baseline and 52 weeks
Other outcomes:
measure: Osteogenic potential
timeFrame: 52 weeks
Locations:
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
References: