REVIEW article
Front. Clin. Diabetes Healthc.
Sec. Diabetes Multiorgan Complications
Volume 6 - 2025 | doi: 10.3389/fcdhc.2025.1657710
This article is part of the Research TopicReviews in Clinical Diabetes and HealthcareView all 12 articles
Ferroptosis and pyroptosis in diabetes mellitus: emerging therapeutic potential of GLP-1 receptor agonists
Provisionally accepted
- 1Demokriteio Panepistemio Thrakes - Panepistemioupole Alexandroupoles, Alexandroupoli, Greece
- 2Universita degli Studi di Palermo, Palermo, Italy
- 3Univerziteta u Novom Sadu Medicinski Fakultet, Novi Sad, Serbia
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Ferroptosis and pyroptosis are two emerging forms of regulated cell death. The former encompasses cell death by excessive accumulation of lipid hydroperoxides in an iron-dependent way. The latter pertains to inflammation-associated cell death following activation of caspase-1, caspase-11/4/5 through Gasdermin D (GSDMD). Recent evidence confirms the implication of ferroptosis and pyroptosis in diabetes mellitus (DM) and its complications, notably diabetic kidney disease (DKD), and also in metabolic-dysfunction associated liver disease (MASLD). The aim of this narrative review was to summarise current experimental evidence on the potential beneficial actions of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in DM and diabetic complications via reduction of ferroptosis and pyroptosis. Data point to their therapeutic potential in DKD and MASLD. Treatment with GLP-1RAs was comparable with ferrostatin-1 (Fer-1), a well-known-ferroptosis inhibitor: ferroptosis-associated markers (e.g. Acyl-CoA Synthetase Long Chain Family Member 4, ASCL4) were decreased and factors alleviating ferroptosis were increased. Similarly, caspase-1, GSDMD, interleukin-1β (IL-1β) and/or nucleotide-binding oligomerisation domain, leucine-rich repeat-containing receptor-containing pyrin domain 3 (NLPR3), which induce pyroptosis, were restored following GLP-1RAs therapy. The pleiotropic effects of GLP-1RAs included improvements in inflammatory markers, fibrosis-associated indices, mitochondrial ultrastructure and oxidative stress. Nevertheless, these positive effects mediated by GLP-1RAs are almost exclusively based on experimental models. Therefore, clinical trials are required to explore these promising outcomes in clinical practice.
Keywords: ferroptosis, pyroptosis, Diabetes Mellitus, Diabetic kidney disease, metabolic-dysfunction associated liver disease, glucagon-like peptide 1 receptor agonists
Received: 01 Jul 2025; Accepted: 17 Sep 2025.
Copyright: © 2025 Panou, Gouveri, Rizzo, Popovic and Papanas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Nikolaos Papanas, papanasnikos@yahoo.gr
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.