Repurposing metformin as a potential treatment for inflammatory bowel disease: Evidence from cell to the clinic

Wanchaitanawong, Wasuwit; Thinrungroj, Nithi; Chattipakorn, Siriporn C.; Chattipakorn, Nipon; Shinlapawittayatorn, Krekwit

doi:10.1016/j.intimp.2022.109230

Cited by 19 publications

(11 citation statements)

References 78 publications

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“…In addition, in a mouse model of colorectal cancer induced by Fusobacterium nucleatum , which is enriched in colorectal carcinogenesis, metformin decreases tumour size and the abundance of F. nucleatum in tumour tissue 142 . Additionally, the use of metformin in the treatment of inflammatory bowel disease demonstrated positive effects through its action on inflammatory pathways, intestinal barrier integrity and gut microbiota 143 . Metformin increased the relative abundance of Lactobacillus and Akkermansia species and alleviated gut dysbiosis, colonic inflammation and mucus barrier disruption induced by experimental colitis 123 , 144 .…”

Section: Metformin and Microbiota Interactionsmentioning

confidence: 99%

Metformin: update on mechanisms of action and repurposing potential

2023

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Currently, metformin is the first-line medication to treat type 2 diabetes mellitus (T2DM) in most guidelines and is used daily by >200 million patients. Surprisingly, the mechanisms underlying its therapeutic action are complex and are still not fully understood. Early evidence highlighted the liver as the major organ involved in the effect of metformin on reducing blood levels of glucose. However, increasing evidence points towards other sites of action that might also have an important role, including the gastrointestinal tract, the gut microbial communities and the tissue-resident immune cells. At the molecular level, it seems that the mechanisms of action vary depending on the dose of metformin used and duration of treatment. Initial studies have shown that metformin targets hepatic mitochondria; however, the identification of a novel target at low concentrations of metformin at the lysosome surface might reveal a new mechanism of action. Based on the efficacy and safety records in T2DM, attention has been given to the repurposing of metformin as part of adjunct therapy for the treatment of cancer, age-related diseases, inflammatory diseases and COVID-19. In this Review, we highlight the latest advances in our understanding of the mechanisms of action of metformin and discuss potential emerging novel therapeutic uses.

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Section: Metformin and Microbiota Interactionsmentioning

confidence: 99%

Metformin: update on mechanisms of action and repurposing potential

2023

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“…Furthermore, metformin’s capacity to restore gut microbiota in mice with colitis led to a reduction in intestinal inflammation. 45 Moreover, oral glucosamine demonstrated anti-inflammatory effects in an experimental model of IBD. 46 This suggested that glucosamine could potentially serve as a new functional food for individuals with IBD and may help in managing stricturing disease.…”

Section: Discussionmentioning

confidence: 99%

Drug Repurposing in Crohn’s Disease Using Danish Real-World Data

Shakibfar,

Allin,

Jess

et al. 2024

POR

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Aim Drug repurposing, utilizing electronic healthcare records (EHRs), offers a promising alternative by repurposing existing drugs for new therapeutic indications, especially for patients lacking effective therapies. Intestinal fibrosis, a severe complication of Crohn’s disease (CD), poses significant challenges, increasing morbidity and mortality without available pharmacological treatments. This article focuses on identifying medications associated with an elevated or reduced risk of fibrosis in CD patients through a population-wide real-world data and artificial intelligence (AI) approach. Methods Patients aged 65 or older with a diagnosis of CD from 1996 to 2019 in the Danish EHRs were followed for up to 24 years. The primary outcome was the need of specific surgical procedures, namely proctocolectomy with ileostomy and ileocecal resection as proxies of intestinal fibrosis. The study explored drugs linked to an increased or reduced risk of the study outcome through machine-learning driven survival analysis. Results Among the 9179 CD patients, 1029 (11.2%) underwent surgery, primarily men (58.5%), with a mean age of 76 years, 10 drugs were linked to an elevated risk of surgery for proctocolectomy with ileostomy and ileocecal resection. In contrast, 10 drugs were associated with a reduced risk of undergoing surgery for these conditions. Conclusion This study focuses on repurposing existing drugs to prevent surgery related to intestinal fibrosis in CD patients, using Danish EHRs and advanced statistical methods. The findings offer valuable insights into potential treatments for this condition, addressing a critical unmet medical need. Further research and clinical trials are warranted to validate the effectiveness of these repurposed drugs in preventing surgery related to intestinal fibrosis in CD patients.

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“…Further, several studies indicate that metformin helps reduce the symptoms associated with inflammatory bowel disease as well as colitis in diabetic and non-diabetic patients [113]. Moreover, type-2 diabetes patients on metformin treatment have a reduced risk of developing IBD [114].…”

Section: Metformin In Controlling Infectious Diseases Including Covid-19mentioning

confidence: 99%

Anti-Inflammatory Potential of the Anti-Diabetic Drug Metformin in the Prevention of Inflammatory Complications and Infectious Diseases Including COVID-19: A Narrative Review

Plowman,

Christensen,

Aiges

et al. 2024

IJMS

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Metformin, a widely used first-line anti-diabetic therapy for the treatment of type-2 diabetes, has been shown to lower hyperglycemia levels in the blood by enhancing insulin actions. For several decades this drug has been used globally to successfully control hyperglycemia. Lactic acidosis has been shown to be a major adverse effect of metformin in some type-2 diabetic patients, but several studies suggest that it is a typically well-tolerated and safe drug in most patients. Further, recent studies also indicate its potential to reduce the symptoms associated with various inflammatory complications and infectious diseases including coronavirus disease 2019 (COVID-19). These studies suggest that besides diabetes, metformin could be used as an adjuvant drug to control inflammatory and infectious diseases. In this article, we discuss the current understanding of the role of the anti-diabetic drug metformin in the prevention of various inflammatory complications and infectious diseases in both diabetics and non-diabetics.

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Repurposing metformin as a potential treatment for inflammatory bowel disease: Evidence from cell to the clinic

Cited by 19 publications

References 78 publications

Metformin: update on mechanisms of action and repurposing potential

Metformin: update on mechanisms of action and repurposing potential

Drug Repurposing in Crohn’s Disease Using Danish Real-World Data

Anti-Inflammatory Potential of the Anti-Diabetic Drug Metformin in the Prevention of Inflammatory Complications and Infectious Diseases Including COVID-19: A Narrative Review

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