The effect of oral Semaglutide on bone turnover in patients with T2D: a randomized placebo-controlled clinical trial (SOBER II)

Prior treatment

• Antiresorptive or bone anabolic drugs for the last 12 months
• Use of anabolic steroids in the previous year
• Stable therapy with DPP4 inhibitors (unless the patient is willing to discontinue the treatment)
• Previous bariatric surgery

Other illness

• 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.
• History of pancreatitis
• Allergy or hypersensitivity to the active substance or to any of the ingredients
• Type 1 diabetes mellitus
• Congestive heart failure (NYHA Class IV)
• History of gastrointestinal surgery (except uncomplicated surgical procedures such as hernia surgery and appendectomy)

Lab values

• 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.

Other

• Use of GLP-1Ras within 90 days
• Inability to give informed consent
• BMI <20 kg/m2 or BMI>37 kg/m2
• 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.
• Primary hyperparathyroidism
• Vitamin D deficiency (<25 nM) (re-test after substitution acceptable)

• Type 2 diabetes and glycosylated haemoglobin (HbA1C) of 44-91 mmol/mol (6.2-10.5%) and
• T-score </=+1 in hip or lower back, assessed by DXA scan and / or
• Low-energy fracture within the last 3 years