metformin

These findings suggest that IME may represent a novel approach for targeting IL-16 and energy metabolism in the treatment of MM.

P1, N=48, Not yet recruiting, Otsuka Pharmaceutical Development & Commercialization, Inc.

P1, N=41, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Trial completion date: Nov 2026 --> Apr 2026 | Trial primary completion date: Jul 2026 --> Feb 2026

Molecular docking revealed that piperine binds at the AMPK α-β interface (ADaM-like site) with a favorable binding affinity (- 6.3 kcal/mol), comparable to the reference AMPK activator metformin (- 6.8 kcal/mol)...Cell cycle analysis revealed a marked arrest at the G2/M phase (~ 20-22%).Additionally, piperine significantly inhibited cancer cell migration, reducing wound closure at 24 h to 29.5 ± 0.3% (50 µM) and 18.8 ± 0.2% (100 µM) compared to 45.3 ± 0.4% in controls, and at 48 h to 48.1 ± 0.2% and 27.6 ± 0.3%, respectively (control: 72.4 ± 0.6%). Collectively, these findings demonstrate that piperine effectively modulates AMPK signaling, correlating with apoptosis induction, cell-cycle arrest, and impaired migratory capacity in breast cancer cells, thereby highlighting its potential as an AMPK-targeting therapeutic candidate for luminal A breast cancer.

ZO can markedly reduce the pathological effects of the retina in a diabetic rat model.

In addition, a significant correlation between nitrosative stress, glycemia, inflammation, glycogen depletion, TIMP-1, and collagen deposition (fibrosis) was observed. These findings demonstrate that diabetes adversely affects hepatic glycogen stores and causes liver tissue injury, as well as upregulating the TNF-α/iNOS/TIMP-1 fibrosis axis while being protected by metformin.

P4, N=176, Not yet recruiting, Mansoura University

In this study, we constructed a biomimetic delivery system (CMCMCDR) coated with CT26 tumor cell membranes, loaded with copper metformin carbon dots (CuMCDs), doxorubicin (DOX), and Toll-like receptor 7 (TLR7) agonist R837. In the dual-tumor model, CMCMCDR targets tumors, inhibits primary tumor growth, and blocks distant metastasis by activating systemic immunity. This study confirms that CMCMCDR synergistically improves hypoxia and immunosuppression through CDT/PTT/PDT and R837-mediated immunoregulation, providing a strategy for combating tumor metastasis and recurrence.

Emerging strategies, including metformin, novel AMPK activators, and LKB1-based gene therapies, are highlighted as promising yet challenged by tissue specificity, off-target effects, and genetic variation. By integrating insights from cardiovascular, metabolic, neurological, and oncological research, this review underscores the pathway's potential as both a biomarker source and therapeutic target, providing a foundation for precision medicine in complex diseases.

Metformin may prevent colorectal cancer via the AMPKγ1 (PRKAG1) target based on genetic evidence, supporting the evaluation of metformin use in colorectal cancer prevention using randomised controlled trials.

Finally, we highlight promising therapeutic avenues that target glial pathways, such as interleukin-35 (IL-35), β-hydroxybutyrate, and metformin, which aim to shift the treatment paradigm from symptomatic control to disease modification. By integrating preclinical and clinical insights, this review proposes the glial triad as a central player in PDN and suggests that targeted glial interventions may represent a promising frontier for future disease-modifying strategies.

Compounds such as metformin, rapamycin, anti-inflammatories, GLP-1 agonists, senolytics, spermidine, SGLT2 inhibitors, and sirtuin activators have shown lifespan extension in animal models. Notably, the gut microbiome may serve as both a mediator and modulator of these interventions, influencing drug metabolism, efficacy, and host responses. This review synthesizes current evidence on the gut microbiome's role in aging, examining its role as both mediator and modulator of longevity interventions and how microbiome-associated mechanisms intersect with emerging anti-aging therapeutics.