In vivo, metformin inhibited tumor growth, which was negated by RBMS3 silencing. Our findings suggest that metformin promotes ferroptosis and inhibits ovarian cancer progression by upregulating RBMS3, offering a promising direction for clinical application in ovarian cancer treatment.

P4, N=96, Recruiting, Bahria University | Active, not recruiting --> Recruiting

However, the high glucose metabolism in inflammatory lesions, driven by macrophage activation, aggregation, and the release of inflammatory factors, is a primary source of false-positive results in FDG PET/CT oncology. This significantly diminishes the specificity and accuracy of PET/CT in diagnosing and staging lung cancer.Here we show FoxO1 plays a role in glucose metabolism in macrophages.We found that metformin regulated FoxO1 expression in macrophages, regulated the expression of inflammatory mediators and apoptosis of macrophages, thus reducing inflammatory glucose metabolism and improving the diagnostic accuracy of 18F-FDG PET/CT in lung cancer.We anticipate that our study could provide a credible approach to improve tumor diagnostic accuracy with PET/CT.

These findings suggest that of HA-Se@CPT, Met, and GW280264X may inhibit tumor progression in BC by improving the function and infiltration of CD8+ T cells. Their effect is more pronounced when used in combination.

P4, N=20, Recruiting, University of Virginia | Not yet recruiting --> Recruiting

P2, N=0, Withdrawn, Poxel SA | Phase classification: P2a --> P2 | N=24 --> 0 | Not yet recruiting --> Withdrawn

P1/2, N=85, Recruiting, Minia University | Not yet recruiting --> Recruiting

This study emphasizes the importance of personalized approaches in the use of MAL-PDT, tailoring treatment according to tumor-specific characteristics. Biomarkers such as p53, β-catenin, and GLUT1 can serve as predictive tools for PDT response, helping clinicians identify patients who may benefit from alternative or combined treatments to enhance therapeutic efficacy.

Additionally, metformin reversed the irradiation-induced reduction in the abundance of Lactobacillus and Lachnospiraceae at the genus level. Our findings indicated that metformin ameliorates RILF by downregulating the inflammatory-related HMGB1/TLR4/NF-κB pathway and improving intestinal flora disorder.

We established an in vivo POCD model using isoflurane inhalation anesthesia with exploratory laparotomy...Finally, the PI3K inhibitor, LY294002, reversed the effects of metformin on the levels of PI3K, AKT phosphorylation, and BDNF in vitro cultured HT-22 cells...These results reveal that metformin may alleviate POCD by modulating the PI3K/AKT/BDNF axis. Our study may provide a novel strategy for preventing and treating POCD with this medication.

P1/2, N=85, Not yet recruiting, Minia University

These data reveal early-postmenopause as a critical window when metformin decreases progression of existing disease and highlights the importance of maintaining treatment to prevent metabolic dysregulation, which could promote secondary tumors/metastasis. These findings also help explain the disconnect between epidemiological studies reporting anticancer benefits of metformin and more recent clinical trials that failed to see similar efficacy, potentially due to issues of timing and/or inclusion of women outside the early postmenopausal window and/or without underlying metabolic dysfunction.

Mechanistically, the co-treatment with drugs-loaded Cs NPs was found to downregulate the expression of NOTCH-1 and HIF-1α, two key transcription factors involved in tumor cell survival and adaptation, suggesting that their inhibition is a crucial component of the therapeutic efficacy of this treatment strategy. Collectively, the findings of this study suggest that the co-delivery of Met and Dig via chitosan Cs NPs represents a promising therapeutic strategy for breast cancer, as it effectively targets key pathways involved in tumor growth and progression, and underscores the potential of Cs NPs as a versatile platform for cancer therapy.

P=N/A, N=92, Not yet recruiting, RenJi Hospital

In conclusion, this study provides new insights into the involvement of MetF in ionic interactions with VDAC1, contributing to its anticancer effects in HCC. These findings help elucidate the diverse biological and pharmacological effects of MetF, particularly its influence on autophagy, as well as the potential of MetF as a therapeutic agent for diseases characterized by VDAC1 overexpression.

Presenilin enhancer gamma-secretase subunit (PSENEN), the straight target of metformin, is highly expressed in several cancers...PSENEN may be involved in regulating the immune microenvironment of KIRC, and oxidative phosphorylation may also be a pathway for its involvement in cancer development. PSENEN is a novel prognostic marker for KIRC.

P=N/A, N=70, Not yet recruiting, University of Health Sciences Lahore

Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC, and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.

The study investigated qBOLD imaging's accuracy in identifying hypoxia status within glioblastoma. qBOLD effectively assesses hypoxia and its dynamic evolution in glioblastoma. qBOLD parameters assist in identifying a suitable patient demographic for metformin treatment.

Our results show that wogonin not only impedes cancer cell growth and mobility both in vitro and in vivo but also significantly increases the cytotoxicity of cisplatin...These results indicate that wogonin promotes DNA demethylation by stabilizing TET2. In conclusion, our findings highlight not only the therapeutic potential of wogonin but also its preventative capability against ovarian cancer in individuals with metabolic disorders, such as diabetes, who are at increased risk of ovarian cancer.

P2/3, N=326, Active, not recruiting, Columbia University | Recruiting --> Active, not recruiting

In vivo experiments using CRC-bearing mouse models, the results confirmed the anti-tumor efficacy of the COMB, leading to substantial inhibition of tumor growth without inducing general toxicity. In conclusion, our study suggests that combining CUR with MET holds promise as a potential option for CRC treatment, with critical mechanisms likely involving ROS elevation, autophagy, and ferroptosis.

Met exerted inhibitory effects on PC through the miR-378a-3p/VEGFA/RGC-32 pathway. Strategies targeting the miR-378a-3p/VEGFA/RGC-32 axis represent a novel avenue for the prevention and treatment of PC.

Metformin inhibited colorectal tumorigenesis by suppressing the TLR4/MyD88/NFκB/MAPK pathway, modulating macrophage M2 polarization and increasing SCFA levels. It holds promise as a potentially effective treatment for colorectal cancer.

In individuals with prediabetes and well-controlled T2D, carnosine supplementation did not result in any significant changes in inflammatory markers. Larger RCTs with longer follow-up durations are needed to evaluate whether carnosine may be beneficial in individuals with poorly controlled T2D.

Thereafter, the pre-diabetic animals were sub-divided into five groups (n = 6), where they were either orally treated with GTIN (15 mg/kg) or metformin (MET) (500 mg/kg), both in the presence and absence of dietary intervention for 12 weeks...These findings may suggest that GTIN administration in both the presence and absence of dietary intervention may offer therapeutic potential in ameliorating cardiovascular disturbances associated with the PD state. However, future studies are needed to determine the physiological mechanisms by which GTIN improves cardiovascular function in the PD state.

P1, N=14, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

P3, N=60, Completed, Tanta University | Recruiting --> Completed | Trial completion date: Oct 2023 --> Jun 2024 | Trial primary completion date: Oct 2023 --> Jun 2024

P1, N=14, Recruiting, Boehringer Ingelheim | Not yet recruiting --> Recruiting

P4, N=96, Active, not recruiting, Bahria University | Not yet recruiting --> Active, not recruiting

P=N/A, N=1017, Active, not recruiting, Massachusetts General Hospital | Trial primary completion date: Dec 2023 --> Dec 2024

P4, N=6, Terminated, Columbia University | N=46 --> 6 | Active, not recruiting --> Terminated; Poor enrollment

5-Fluorouracil (5-FU) chemoresistance contributes to poor therapeutic response and prognosis of gastric cancer (GC), for which effective strategies to overcome chemoresistance are limited. In addition, NIT2 expression negatively correlated with H3K14ac and OXPHOS and positively correlated with the chemotherapeutic responses and prognosis of patients with GC. Our findings reveal the moonlighting function of NIT2 in chemoresistance and underscore that OXPHOS blockade by metformin enhances 5-FU chemosensitivity upon NIT2 loss.

The gut-liver axis represents a potential therapeutic target, with metformin showing promise in modulating the gut microbiome and enhancing intestinal barrier function...Current large-scale studies on glucocorticoid therapy for sepsis have yielded mixed results, likely due to inadequate assessment of the immune status of the host. Future research should prioritize the development of personalized immunotherapy tailored to patients' immune profiles, focusing on identifying novel indicators of immune status and advancing immunomodulatory targets and therapeutics for septic patients.

Overall, LINC00094 expression may regulate melanoma cell growth and motility by modulating the expression of miR-1270, and targeting genes of CD276 and CENPM indicating its therapeutic potential in melanoma treatment.

We highlight that the combination of ReoT3D- derived secretome with Irinotecan and Metformin showed a synergistic anti-cancer effect on the CT26 cell line, and this strategy may be considered as a new approach against colorectal cancer (CRC) in the in vitro and in vivo in future studies.

Metformin (MET), a commonly used oral drug for type 2 diabetes, has played a vital role in fostering an immunostimulatory environment...Based on the function of MET, there is a marked increase in the infiltration of activated CD8+ T cells and NK cells, which subsequently augments ferroptosis to a greater extent. Taken together, Fe-PDA-MET NPs activate a ferroptotic positive-feedback loop for effectively control TNBC progression, which offers a promising therapeutic modality to enhance the immunogenicity and reshape the TIME.

GDF15 is a plasma marker that responds to the treatment of unresected LA-NSCLC with cCRT and metformin. GDF15 levels correspond with tumor volume and increased GDF15 levels predict for poor RFS and OS. These results require validation in larger clinical trial datasets.

Meanwhile, metformin significantly inhibited NCI-H460 xenograft tumor growth in nude mice, increased GDF15 expression, and regulated EMT- and migration-related protein expression in xenograft tumors. In conclusion, our results provide novel insights into revealing that GDF15 can serve as a potential molecular target of metformin owing to its anti-cancer effect in NSCLC, which is mediated by AMPK activation.

Loading the hydrogel with mitoxantrone (MTX) and metformin (MET) further enhances the therapeutic effect by combining chemotherapy with PD-L1 downregulation. Mechanistically, KFM promotes PD-L1 degradation via a ubiquitin-dependent pathway. This "carrier-free" delivery system expands the role of supramolecular hydrogels beyond passive carriers to active immunotherapeutic agents, offering a promising new strategy for cancer therapy.

Small-molecule inhibition of mitochondrial respiration-using glyceollin I, metformin, or phenformin-induced overproduction of the oncometabolite lactate, which acidified the extracellular milieu and repressed the expression of homologous recombination (HR)-associated DNA repair genes...These effects were selective to breast cancer cells; normal epithelial cells retained HR proficiency and cell viability. These mechanistic insights into the BRCAness-prone properties of breast cancer cells support the therapeutic utility and cancer cell-specific potential of mitochondria-targeting drugs.

The anti-inflammatory experiments demonstrated strong inhibition of NO release, transcriptional downregulation of classical effective cellular factors tumour necrosis factor-α, interleukin-6, interleukin-1β, and transcriptional upregulation of interleukin-10 in LPS-induced RAW264.7 cells. Its stronger anti-inflammatory activity than quercetin provided a reference for modifying the structure of quercetin to obtain more compounds with better pharmacological activities for medical industry.