Pancreatic safety of DPP-4 inhibitors in type 2 diabetes millitus: A protocol for systematic review and network meta-analysis.

BACKGROUND: Dipeptidyl-peptidase IV inhibitor (DPP-4i) is a common hypoglycemic medication in treating type 2 diabetes millitus. It has become widely utilized in clinical practice due to its ability to effectively manage blood glucose while posing a low risk of hypoglycemia and weight gain. However, there is no consensus on DPP-4i's pancreatic safety due to a paucity of clinical evidence. The safe event appears to be easily overlooked. This review aims to evaluate the pancreatic safety of DPP-4i in patients with type 2 diabetes mellitus using the standard pairwise and network meta-analysis methods. METHODS: MEDLINE, Embase, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials will be used to search for published literature on the pancreatic safety of DPP-4 inhibitors in type 2 diabetes millitus, and clinical trial registries will be used to look for unpublished trials. Two independent reviewers will screen literature for eligibility, extract available data, and assess the risk of bias. All divergences will be resolved after rechecking the source papers and further discussion among the reviewers with a complete consensus before inclusion. The risk of bias will be assessed by the Cochrane bias risk tool, and the quality of evidence will be interpreted by the GRADE Working Group approach. We will use STATA16.0 and WinBUGS1.4.3 for paired meta-analysis and Bayesian network meta-analysis. RESULTS: This study will evaluate the pancreatic safety of DPP-4 inhibitors in type 2 diabetes millitus. CONCLUSION: This systematic review and network meta-analysis will evaluate the pancreatic safety of DPP-4i in patients with type 2 diabetes millitus. The findings of this study may supplement the evidence-based information on DPP-4i, improve existing understanding of this issue, and assist patients and clinicians in making better treatment decisions by raising their awareness of the problem. PROTOCOL REGISTRATION NUMBER: INPLASY202230014.

Network pharmacology-based investigation of potential targets of astragalus membranaceous-angelica sinensis compound acting on diabetic nephropathy.

To explore the mechanism of the Astragalus membranaceous (AM)-Angelica sinensis (AS) compound in the treatment of diabetic nephropathy (DN) we used network pharmacology and molecular docking. Screen the components and targets of the AM-AS compound in the TCMSP and the BATMAN-TCM, and establish a component-target interaction network by Cytoscape 3.7.2. After searching relevant targets of DN in related databases, the common targets of the AM-AS compound and DN were obtained by comparison. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis were performed through David database. Molecular docking was performed by PyMoL2.3.0 and AutoDock Vina software. After screening, 142 main targets of the AM-AS compound in the treatment of DN have been identified. Target network was established and the topology of PPI network was analyzed. KEGG pathway enrichment analysis shows that these targets are related to apoptosis, oxidative stress, inflammation, insulin resistance, etc. Molecular docking shows that the target proteins have good combinations with the main active components of the AM-AS compound. AM-AS compound may treat DN by acting on VEGFA, TP53, IL-6, TNF, MARK1, etc., and regulate apoptosis, oxidative stress, inflammation, glucose, and lipid metabolism processes. The in vivo study results suggest that AM-AS compound can significantly reduce the FBG level of diabetic rats, increase the level of INS, improve renal functions, reduce urinary proteins, inhibit glycogen deposition, granulocyte infiltration and collagen fiber proliferation in renal tissue, and restrain the progress of DN. In vivo study combined with network pharmacology and molecular docking methods provides new ideas for the pathogenesis and treatments of DN.