Short summary

This randomized placebo-controlled clinical trial aims to uncover the effects of 52 weeks of treatment with once daily dosis of oral GLP-1Ra semaglutide (a anti-diabetic drug) or matching placebo on bone formation in 64 patients with type 2 diabetes. Effects will be assessed by changes in bone turnover, strength, microarchitecture and bone mineral density.

Rationale

Glucagon-like peptide-1 (GLP-1) is an intestinal hormone produced by enteroendocrine L-cells located primarily in the ileum and colon that is released in response to food intake. GLP-1 amplifies insulin secretion, suppresses glucagon release, and delays gastric emptying. GLP-1 receptor agonists (GLP-1 RAs) augment bone mass and ameliorate bone strength in ovariectomy-induced bone loss and type 2 diabetes mellitus (T2D) rodent models. T2D is associated with increased fracture risk. Treatment with the GLP-1 RA liraglutide for 26 weeks preserved bone mineral density (BMD) at the hip despite weight loss in patients with T2D and increased bone mineral content after weight loss in women. Furthermore, treatment with liraglutide for at least 52 weeks is associated with lower fracture risk.

The aim of this trial is to investigate if semaglutide a long-acting GLP-1RA, improves bone formation and strength in men and women aged 50-85 years with T2D and low bone mass. Treatment involves oral administration of semaglutide once daily or matching placebo. The primary outcome is bone formation assessed using a circulating serum biomarker, and the secondary outcomes are bone strength assessed using microindentation, biomarker of bone resorption, BMD at the hip and lumbar spine, bone microstructure, and bone remodelling. The duration of the trial is 52 weeks.

Description of the cohort

Men and women with type 2 diabetes, age 50-85 years (women menopause for > 5 years) AND low bone mass assessed by either DXA-scan (T-score between -1 and -2.5) or a low energy fracture within the last 3 years.

Data and biological material

We use biomarkers for bone formation and bone resorption measured in fasting blood samples. Furthermore, we assess bone strength by direct strength measurement using microindentation, and bone microarchitecture and bone mass density using HR-pQCT resp. DXA-scans.

Collaborating researchers and departments

GCP-unit Odense, OPEN Odense, OUH

• Tanja Bidstrup
• Josephine Malmström Kroman

Department of Clinical Biochemestry

• Line Weis Andersen

Steno Diabetes Center Odense