Diabetology International · Oct 31, 2026

Baseline monocyte GIP receptor mRNA expression is associated with reductions in body weight and FIB-4 index after switching to tirzepatide in patients with type 2 diabetes

By Okuma H

Background: Tirzepatide improves body weight and glycemic control in patients with type 2 diabetes, but factors associated with inter-individual differences after switching remain unclear. We examined whether baseline monocyte glucose-dependent insulinotropic polypeptide receptor (GIPR) mRNA expression was associated with changes in body weight and the fibrosis-4 (FIB-4) index after switching from glucagon-like peptide−1 receptor agonists (GLP-1RAs) to tirzepatide. Methods: This single-center retrospective study included 90 patients with type 2 diabetes who had received a GLP-1RA for at least 6 months before switching. Baseline monocyte GIPR mRNA expression was measured by quantitative real-time polymerase chain reaction. Associations with percentage body-weight change and FIB-4 index change during the 6 months after tirzepatide initiation were assessed by correlation and multivariable regression. Exploratory ex vivo assays were performed to assess monocyte responses to native GIP. Results: Higher baseline monocyte GIPR mRNA expression was associated with greater reductions in body weight and the FIB-4 index and remained significant in multivariable models. The association with the FIB-4 index remained significant after additional adjustment for percentage body-weight change at 6 months after tirzepatide initiation. GIPR mRNA expression was not associated with body-weight change during the preceding 6 months of GLP-1RA therapy. Native GIP suppressed lipopolysaccharide-induced interleukin-6 and tumor necrosis factor-alpha responses in monocytes. Conclusions: Baseline monocyte GIPR mRNA expression was associated with body-weight and FIB-4 index reductions after switching to tirzepatide. It may represent an exploratory marker of clinical changes, but treatment specificity, causal GIPR-dependent mechanisms, and structural liver fibrosis regression were not established. Graphical abstract: Summary of the study design and main finding. Baseline GIPR mRNA expression in peripheral blood monocytes was associated with reductions in body weight and the FIB-4 index after switching to tirzepatide in patients with type 2 diabetes. In exploratory ex vivo assays, native GIP suppressed LPS-induced inflammatory responses, supporting monocyte GIPR expression as a candidate exploratory marker requiring further validation.

doi.org/10.1007/s13340-026-00940-3 Open access PubMed 42968811 Interventions