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.

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