P=N/A, N=300, Not yet recruiting, Ohio State University | Initiation date: Sep 2024 --> Dec 2024

P2, N=14, Not yet recruiting, Amsterdam UMC, location VUmc

P3, N=124, Recruiting, Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting --> Recruiting

P=N/A, N=40, Not yet recruiting, Sheba Medical Center | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

P2, N=76, Not yet recruiting, Assistance Publique - Hôpitaux de Paris

P4, N=200, Not yet recruiting, Stanford University

P1, N=64, Active, not recruiting, University of Utah | Trial completion date: Apr 2025 --> Nov 2025 | Trial primary completion date: Apr 2024 --> Nov 2025

P=N/A, N=200, Recruiting, Nanchang Reproductive Hospital (Affiliated Reproductive Hospital of Jiangxi University of Traditional Chinese Medicine); Nanchang Reproductive Hospita

P4, N=80, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University; Second Affiliated Hospital, School of Medicine, Zhejiang University

These results were also confirmed through an in vivo mouse xenograft CRC model, in which combined treatment with metformin and TRAIL induced tumor cell death, thus demonstrating the anticancer effect of their coadministration. Therefore, cotreatment of metformin and TRAIL could be an effective anticancer treatment strategy for TRAIL-resistant CRC.

P1, N=180, Recruiting, University of Alberta | Suspended --> Recruiting

This study highlights distinct differences in inflammatory markers and systemic complications between T2DM patients treated with insulin and those treated with metformin alone. Further research is needed to explore the mechanisms underlying these observations and optimize treatment strategies for T2DM patients.

Metformin may serve as a targeted therapeutic agent in HER2-positive breast cancer by modulating the miR-125a-HER2 axis and influencing on the epigenetic and EMT regulation. Further research is warranted to elucidate the therapeutic potential of metformin through these mechanisms.

P=N/A, N=254, Enrolling by invitation, RenJi Hospital

P=N/A, N=138, Completed, Garvan Institute of Medical Research | Active, not recruiting --> Completed | N=264 --> 138 | Trial primary completion date: Jul 2024 --> Dec 2023

Tiliroside (25), boehmenan (30), boehmenan H (31), and isoquercetin (22) elicited the highest binding affinity toward the enzyme with a score of -10.4, -10.4, -10.2 and -10.1 Kcal/mol compared to the reference drug erlotinib having a binding score equal to -9 Kcal/mol...Overall, the current study presents helpful insights into the pharmacokinetic and pharmacodynamic properties of the reported cytotoxic metabolites belonging to family Malvaceae members. The molecular docking and dynamic simulations results intensify the roles of secondary metabolites from medicinal plants in fighting cancer.

Metformin lowers the risk of tumour development through various mechanisms, including the adenosine 5'-monophosphate-activated protein kinase/liver kinase B1/mechanistic target of rapamycin (AMPK/LKB1/mTOR) pathway, insulin-like growth factor-1 receptor pathway, apoptosis, and autophagy. However, research findings are not entirely consistent. This article reviews the research progress of metformin in terms of lung cancer treatment within the past few years, aiming to provide a more comprehensive understanding of how metformin exerts its anti-cancer impact and how it can be clinically applied, as well as provide new insights for lung cancer treatment.

Our findings suggest that combining metformin with doxorubicin can enhance the anticancer activity of doxorubicin and decrease its cytotoxicity in a 4T1 breast cancer mouse model.

Metformin related gastrointestinal adverse effects are associated with dose escalation, immediate release formulations, gut microbiota alteration, epigenetic predisposition, inhibition of organic cation transporters in addition to interactions with serotonin, histamine and the enterohepatic circulation. Potentially effective measures to overcome intolerance encompasses carefully objective targeted dose escalation, prescription of fixed dose combination, microbiome modulators and prebiotics, in addition to use of extended release formulations.

P2, N=30, Not yet recruiting, State University of New York at Buffalo | Trial completion date: May 2026 --> Oct 2026 | Initiation date: Aug 2024 --> Jan 2025 | Trial primary completion date: Nov 2025 --> Apr 2026

This finding may also help explain the limited clinical responses to metformin in cancers with RAS mutations. Ultimately, our study underscores the importance of understanding the impact of the genetic landscape in tailoring precision cancer preventive approaches in the context of HNSCC and other cancers that are characterized by the presence of a defined premalignant state and, therefore, amenable for cancer interception strategies.

HMC inhibits lipid accumulation and promotes fatty acid oxidation by AMPK and PPARα pathways in free fatty acid-treated HepG2 cells, thereby attenuating hepatic steatosis.

P2, N=30, Active, not recruiting, University of Guadalajara | Trial completion date: Dec 2024 --> Jul 2025 | Trial primary completion date: Aug 2024 --> Jun 2025

P1, N=14, Not yet recruiting, Boehringer Ingelheim

The effects of metformin in reducing pain can be attributed to many factors, including its anti-inflammatory and antiaging effects. Our findings suggest that metformin may reduce pain and inflammation in patients with OA through the regulation of miR-451/CXCL16 and BCL-2.

Forty-eight 8-week-old female C57BL/6 mice were divided into four groups: group A (control group), group B (model group), group C (model+trimetazidine hydrochloride), and group D (model+metformin group), with 12 mice in each group, by using a randomized numeric table method. Compared with group B, apoptosis rate, JNK, P38 MAPK, CK-MB, BNP, TNF-α, and IL-6 expression were decreased, and LVEF, FS, PKCε, and Cav-3 expression were up-regulated in groups C and D. And group D was better than group C (P<0.05). In conclusion, metformin has a protective effect against septic cardiomyopathy, and the mechanism may be related to the inhibition of the activation of the P38 MAPK/JNK signaling pathway and the up-regulation of PKCε and Cav-3 expression.

P3, N=124, Not yet recruiting, Jiangsu HengRui Medicine Co., Ltd.

PINK1 exhibits low expression levels in patients with diabetic nephropathy and its expression is strongly associated with the inhibition of disease progression, thereby offering significant clinical diagnostic value. Additionally, it may serve as a potential biological marker for clinical diagnosis and treatment of diabetic nephropathy.

In studies conducted on human cells and xenografts, the drug has shown its positive effects in combating these tumors by reducing proliferation, slowing the growth of cancer cells, and inhibiting metastasis. The main goal of this review is to comprehensively summarize the current state of knowledge regarding metformin in the treatment of colorectal cancer and neuroendocrine tumors.

P2, N=18, Active, not recruiting, University of Florida | Trial completion date: Jan 2025 --> Jun 2025

This study provides critical insights into the mechanisms underpinning obesity-mediated EV secretion with oncogenic protein expression, shedding light on their role in EC pathogenesis. Additionally, it offers pre-clinical evidence supporting the initiation of novel studies for EV-targeted therapies aimed at preventing obesity-mediated EC.

P2, N=40, Not yet recruiting, University of Maryland, Baltimore | Trial completion date: Mar 2025 --> Sep 2027 | Trial primary completion date: Jan 2025 --> Jun 2027

P4, N=20, Not yet recruiting, University of Virginia

In conclusion, our results revealed that Atractylodes lancea and atractylodin activated the AMPK signaling pathway, leading to improvements in HFD-induced obesity, fatty liver, and glucose intolerance. This study suggests that the phytochemical, atractylodin, can be a treatment option for MASLD.

However, both autophagy- and LPS-induced inflammation were partially alleviated by RETN treatment. RETN can promote autophagy in BAMs by activating the AMPK/mTOR signaling pathway, it may help prevent LPS-induced inflammation.

P2, N=303, Recruiting, Karolinska Institutet | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2024 --> Jun 2025

P2, N=18, Active, not recruiting, University of Florida | Trial completion date: Aug 2024 --> Jan 2025

P1, N=79, Completed, Zhongnan Hospital

A 63-year-old female with a past medical history of metastatic salivary MECA, type 2 diabetes mellitus previously on metformin, hypertension, and hypothyroidism presented to her oncologist for chemotherapy and was found to have a serum glucose of 30 mg/dL (reference: 65-99)...This case demonstrates that NICTH can be associated with metastatic salivary MECA. The hypoglycemia in this scenario is challenging to manage and is associated with poor prognosis.

These results show that canine CPs exhibit the expression of surrogate markers that suggest sensitivity to metformin, such as upregulated OCT3 and pS6 expression. Taken together, these findings provide the rationale for the early assessment of the use of metformin as a mechanism-based therapeutic approach for treating canine patients with persistent or multiple CPs.

P=N/A, N=100, Recruiting, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine | Not yet recruiting --> Recruiting

P3, N=242, Active, not recruiting, Garvan Institute of Medical Research | Recruiting --> Active, not recruiting