PMID- 35908505 OWN - NLM STAT- MEDLINE DCOM- 20220914 LR - 20220914 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 111 DP - 2022 Oct TI - The impact of SGLT2 inhibitors on inflammation: A systematic review and meta-analysis of studies in rodents. PG - 109080 LID - S1567-5769(22)00564-1 [pii] LID - 10.1016/j.intimp.2022.109080 [doi] AB - BACKGROUND: Inhibition of sodium-glucose cotransporter-2 (SGLT2) has received remarkable attention due to the beneficial effects observed in diabetes mellitus, heart failure, and kidney disease. Several mechanisms have been proposed for these pleiotropic effects, including anti-inflammatory ones. Our systematic review and meta-analysis aimed to assess the effect of SGLT2 inhibition on inflammatory markers in experimental models. METHODS: A literature search was conducted to detect studies examining the effect of SGLT2 inhibitors on inflammatory markers [interleukin-6 (IL-6), C reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and monocyte chemoattractant protein-1 (MCP-1)]. Consequently, a meta-analysis of the included studies was performed, assessing the differences in the levels of the inflammatory markers between the treatment groups as its primary outcome. Moreover, risk of bias, sensitivity analysis and publication bias were evaluated. RESULTS: The systematic literature review yielded 30 studies whose meta-analysis suggested that treatment with an SGLT2 inhibitor resulted in decreases of IL-6 [standardized mean difference (SMD): -1.56, 95% CI -2.06 to -1.05), CRP (SMD: -2.17, 95% CI -2.80 to -1.53), TNF-alpha (SMD: -1.75, 95% CI -2.14 to -1.37), and MCP-1 (SMD: -2.04, 95% CI -2.91 to -1.17). The effect on CRP and TNF-alpha was of lesser magnitude in cases of empagliflozin use. Moderate-to-substantial heterogeneity and possible publication bias were noted. The findings remained largely unaffected after the sensitivity analyses, the exclusion of outlying studies, and trim-and-fill analyses. CONCLUSION: The present meta-analysis suggests that SGLT2 inhibition results in reduction of inflammatory markers in animal models, further validating the suggested anti-inflammatory mechanism of action. CI - Copyright (c) 2022. Published by Elsevier B.V. FAU - Theofilis, Panagiotis AU - Theofilis P AD - 1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece. FAU - Sagris, Marios AU - Sagris M AD - 1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece. FAU - Oikonomou, Evangelos AU - Oikonomou E AD - 1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece; 3rd Cardiology Department, "Sotiria" Regional Hospital for Chest Diseases, University of Athens Medical School, 11527 Athens, Greece. FAU - Antonopoulos, Alexios S AU - Antonopoulos AS AD - 1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece. FAU - Siasos, Gerasimos AU - Siasos G AD - 1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece; 3rd Cardiology Department, "Sotiria" Regional Hospital for Chest Diseases, University of Athens Medical School, 11527 Athens, Greece. FAU - Tsioufis, Konstantinos AU - Tsioufis K AD - 1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece. FAU - Tousoulis, Dimitris AU - Tousoulis D AD - 1st Cardiology Department, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece. Electronic address: drtousoulis@hotmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20220728 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Biomarkers) RN - 0 (Interleukin-6) RN - 0 (Sodium-Glucose Transporter 2) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Animals MH - Anti-Inflammatory Agents/therapeutic use MH - Biomarkers MH - C-Reactive Protein/analysis MH - *Diabetes Mellitus, Type 2/drug therapy MH - Inflammation/drug therapy/metabolism MH - Interleukin-6/metabolism MH - Rodentia/metabolism MH - Sodium-Glucose Transporter 2/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/pharmacology/therapeutic use MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - CRP OT - IL-6 OT - Inflammation OT - MCP-1 OT - SGLT2 inhibitor OT - TNF-alpha COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/08/01 06:00 MHDA- 2022/09/15 06:00 CRDT- 2022/07/31 18:21 PHST- 2022/03/25 00:00 [received] PHST- 2022/06/28 00:00 [revised] PHST- 2022/07/18 00:00 [accepted] PHST- 2022/08/01 06:00 [pubmed] PHST- 2022/09/15 06:00 [medline] PHST- 2022/07/31 18:21 [entrez] AID - S1567-5769(22)00564-1 [pii] AID - 10.1016/j.intimp.2022.109080 [doi] PST - ppublish SO - Int Immunopharmacol. 2022 Oct;111:109080. doi: 10.1016/j.intimp.2022.109080. Epub 2022 Jul 28.