Injection of GIP and GLP-2 may reduce bone resorption biomarker CTX in type 2 diabetes patients: Study

The researchers revealed that the acute effects of exogenous GIP and GLP-2 on bone turnover are also present in patients with T2D, presenting a promising avenue for exploring novel treatment options that could potentially reduce the risk of fractures linked with type 2 diabetes.

"Subcutaneous GIP and GLP-2 affect the bone resorption markers, collagen type 1 C-terminal telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) in individuals with T2D to the same extent as previously demonstrated in healthy individuals," Kirsa Skov-Jeppesen, University of Copenhagen, Copenhagen, Denmark, and colleagues wrote.

Individuals with type 2 diabetes are at increased risk of bone fractures despite normal or increased bone mineral density (BMD). There is no clear understanding of the underlying causes, but could include disturbances in the gut-bone axis, in which GIP and GLP-2 are regulators of bone turnover. Thus, in healthy fasting participants both exogenous GLP-2 and GIP reduce bone resorption.

Against the above background, Dr. Skov-Jeppesen and colleagues aimed to investigate the acute effects of subcutaneously administered GIP and GLP-2 on bone turnover in individuals with T2D.

The study included ten men with type 2 diabetes. Participants met fasting in the morning on three separate test days and were given subcutaneous injections of GIP, GLP-2, or placebo, in a randomized crossover design.

Blood samples were drawn at baseline and regularly after injections. Bone turnover was estimated by circulating CTX, P1NP, sclerostin, and PTH levels.

The study revealed the following findings:

• GIP and GLP-2 significantly reduced CTX to (mean ± SEM) 66 ± 7.8% and 74 ± 5.9% of baseline, respectively, compared with after a placebo.
• P1NP and sclerostin increased acutely after GIP, whereas there was a decrease in P1NP after GLP-2.
• PTH levels decreased to 67 ± 2.5% of baseline after GLP-2 and to only 86 ± 3.4% after GIP.

GIP and GLP-2 injected subcutaneously reduce the bone resorption marker CTX in type 2 diabetes. Additionally, GIP increases the bone formation marker P1NP, whereas GLP-2 decreases it.

"Whether chronic GIP and/or GLP-2 treatments are tied to a reduced fracture risk in individuals with T2D is unexplored but could potentially be a novel treatment option for T2D-associated fracture risk," the researchers concluded.

Reference:

Christiansen, C. B., Hansen, L. S., Windeløv, J. A., Hedbäck, N., Gasbjerg, L. S., Hindsø, M., Svane, M. S., Madsbad, S., Holst, J. J., Rosenkilde, M. M., & Hartmann, B. Effects of Exogenous GIP and GLP-2 on Bone Turnover in Individuals With Type 2 Diabetes. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/clinem/dgae022