The following is a summary of “Effects of Exogenous GIP and GLP-2 on Bone Turnover in Individuals With Type 2 Diabetes,” published in the July 2024 issue of Endocrinology by Skov-Jeppesen, et al.

Individuals with type 2 diabetes (T2D) are at a heightened risk of bone fractures despite having normal or elevated bone mineral density. The exact mechanisms behind this increased risk are not fully understood but may involve disturbances in the gut-bone axis. Both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are known to regulate bone turnover, with exogenous administration of these peptides reducing bone resorption in healthy fasting participants. For a study, researchers sought to investigate the acute effects of subcutaneously administered GIP and GLP-2 on bone turnover in individuals with T2D.

The study involved 10 men with T2D who underwent three separate test days in a randomized crossover design. On each test day, participants were injected subcutaneously with either GIP, GLP-2, or a placebo after fasting overnight. Blood samples were collected at baseline and regular intervals following the injections. Bone turnover was assessed using circulating levels of collagen type 1 C-terminal telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), sclerostin, and parathyroid hormone (PTH).

GIP and GLP-2 significantly reduced CTX levels to (mean ± SEM) 66 ± 7.8% and 74 ± 5.9% of baseline, respectively, compared to the placebo (P = .001). GIP administration resulted in an acute increase in P1NP and sclerostin, whereas GLP-2 decreased P1NP. Additionally, PTH levels decreased to 67 ± 2.5% of baseline following GLP-2 treatment and to 86 ± 3.4% after GIP.

Subcutaneous administration of GIP and GLP-2 affects bone turnover markers CTX and P1NP in individuals with T2D similarly to the effects observed in healthy individuals. It suggested that these peptides modulate bone turnover in a manner consistent with their actions in non-diabetic populations.

Reference: academic.oup.com/jcem/article/109/7/1773/7529176