Context: In healthy individuals, glucose-dependent insulinotropic polypeptide (GIP) enhances insulin secretion and reduces bone resorption by up to 25% estimated by absolute placebo-corrected changes in carboxy-terminal type 1 collagen crosslinks (CTX) during GIP and glucose administration. In patients with type 2 diabetes (T2D), GIP's insulinotropic effect is impaired and effects on bone may be reduced.

Objective: To investigate GIP's effect on bone biomarkers in patients with T2D.

Design: Randomized, double-blinded, crossover study investigating 6 interventions.

Patients: Twelve male patients with T2D.

Interventions: A primed continuous 90-minute GIP infusion (2 pmollkg/min) or matching placebo (saline) administered at 3 plasma glucose (PG) levels (i.e., paired days with "insulin-induced hypoglycemia" (PG lowered to 3 mmol/L), "fasting hyperglycemia" (mean PG similar to 8 mmol/L), or "aggravated hyperglycemia" (mean PG similar to 12 mmol/L).

Main Outcome Measures: Bone biomarkers: CTX, procollagen type 1 N-terminal propeptide (P1NP) and PTH.

Results: On days with insulin-induced hypoglycemia, CTX was suppressed by up to 40 +/- 15% during GIP administration compared with 12 +/- 11% during placebo infusion (P<0.0001). On days with fasting hyperglycemia, CTX was suppressed by up to 36 +/- 15% during GIP administration, compared with 0 +/- 9% during placebo infusion (P<0.0001). On days with aggravated hyperglycemia, CTX was suppressed by up to 47 +/- 23% during GIP administration compared with 10 +/- 9% during placebo infusion (P= 0.0005). At all glycemic levels, P1NP and PHI concentrations were similar between paired days after 90 minutes.

Conclusions: Short-term GIP infusions reduce bone resorption by more than one-third (estimated by absolute placebo-corrected CTX reductions) in patients with T2DM, suggesting preserved bone effects of GIP in these patients.

Precis: Short-term GIP infusions reduce the bone resorption marker CTX by one-third in patients with type 2 diabetes independent of glycemic levels. (C) Endocrine Society 2020.