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For comparisons B and C, ORA was performed using the GOBP database 92 (release 2023) and the Reactome Pathway Knowledgebase 93 (release 2022) to identify over-represented pathways in the upregulated gene sets (padj 0.05 and padj 0.01, respectively)

Phase 2 trials focused on dose-ranging studies to identify optimal therapeutic doses

However, in 2006 it became clear that GIP(3-42) does not function as a physiological antagonist in vivo as its maximal circulating levels are insufficient to elicit antagonistic effects ( At the same time, in 2002, Gipr knockout mice were found to be protected against both obesity and insulin resistance induced by high-fat feeding ( Also in 2002, a GIP analogue with an N-terminal substitution of glutamic acid in position 3 with proline (Pro3), was made as an attempt to prolong the GIP actions by protecting from DPP-4 degradation ( Figure 1 )

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Methods Search strategy and study selection This meta-analysis was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines [16]