Effects of exogenous GIP and GLP-2 on bone turnover in individuals with type 2 diabetes

Kirsa Skov-Jeppesen, Charlotte B Christiansen, Laura S Hansen, Johanne A Windeløv, Nora Hedbäck, Lærke S Gasbjerg, Morten Hindsø, Maria S Svane, Sten Madsbad, Jens J Holst, Mette M Rosenkilde, Bolette Hartmann


CONTEXT: Individuals with type 2 diabetes (T2D) have an increased risk of bone fractures despite normal or increased bone mineral density (BMD). The underlying causes are not well understood but may include disturbances in the gut-bone axis, in which both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are regulators of bone turnover. Thus, in healthy fasting participants, both exogenous GIP and GLP-2 acutely reduce bone resorption.

OBJECTIVE: The objective of this study was to investigate the acute effects of subcutaneously administered GIP and GLP-2 on bone turnover in individuals with T2D.

METHODS: We included 10 men with T2D. Participants met fasting in the morning on three separate test days and were injected subcutaneously with 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 levels of collagen type 1 C-terminal telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), sclerostin, and PTH.

RESULTS: GIP and GLP-2 significantly reduced CTX to (mean ± SEM) 66 ± 7.8% and 74 ± 5.9% of baseline, respectively, compared with after placebo (p = 0.001). In addition, P1NP and sclerostin increased acutely after GIP whereas a decrease in P1NP was seen after GLP-2. PTH levels decreased to 67 ± 2.5% of baseline after GLP-2 and to only 86 ± 3.4% after GIP.

CONCLUSION: Subcutaneous GIP and GLP-2 affect CTX and P1NP in individuals with T2D to the same extent as previously demonstrated in healthy individuals.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Publication statusE-pub ahead of print - 13 Jan 2024


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