metformin / Generic mfg. - LARVOL DELTA

Fish Oil, Metformin and Heart Health in PCOS (clinicaltrials.gov) - P1 | N=146 | Recruiting | Sponsor: University of Alberta | Not yet recruiting ➔ Recruiting

Enrollment open • Atherosclerosis • Cardiovascular • Polycystic Ovary Syndrome • APOB

Impact of combined hormonal contraceptives and metformin on metabolic syndrome in women with hyperandrogenic polycystic ovary syndrome and obesity: The COMET-PCOS randomized clinical trial. (PubMed, PLoS Med) - P3 | "In participants with hyperandrogenic PCOS and overweight/obesity, low-dose COCPs effectively managed PCOS symptoms without increasing prevalence of MetS. Our findings challenge the current practice of using metformin alone or with COCPs for lowering cardiometabolic risk."

Clinical • Journal • Cardiovascular • Genetic Disorders • Metabolic Disorders • Obesity • Polycystic Ovary Syndrome

Metabolic reprogramming drives acquired venetoclax resistance in Acute Myeloid Leukemia and reveals targetable vulnerabilities (ASH 2025) - "In addition, we tested the therapeutic potential of combining venetoclax with metabolic inhibitors, metformin, a mitochondrial complex I inhibitor, and KPT-9274, a NAMPT inhibitor, by calculating synergy scores and quantifying apoptotic responses. These findings support a combinatorial therapeutic strategy targeting both apoptotic and metabolic pathways to overcome acquired venetoclax resistance in AML. Supported by FAPESP, CAPES, and CNPq."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Metabolic Disorders • ANXA5 • BAX • BBC3 • BCL2L1 • BCL2L11 • BID • MCL1 • NAMPT • PMAIP1 • RPS6

A review of immunometabolic crosstalk in PCOS-related pregnancy loss: mechanisms and emerging therapeutic strategies. (PubMed, Gynecol Endocrinol) - "Both translational and clinical for interventions with dual metabolic-immune effects are highlighted, such as metformin, antioxidants likeN-acetylcysteine, anti-androgens, and combination regimens including aspirin with low-molecular-weight heparin (LMWH). PCOS-related miscarriage is increasingly recognized as resulting from dysregulation of immune-metabolic crosstalk. Mechanism-based, multidimensional strategies targeting this dual pathology represent a promising paradigm for preventing and managing pregnancy loss in women with PCOS."

Journal • Review • Genetic Disorders • Metabolic Disorders • Obesity • Polycystic Ovary Syndrome

Emerging Therapies in Autosomal Dominant Polycystic Kidney Disease. (PubMed, Kidney360) - "Tolvaptan, a vasopressin V2 receptor antagonist, established cAMP modulation as a disease-modifying strategy but is limited by aquaretic effects and hepatotoxicity risk...Gene-directed therapies aim to restore polycystin dosage, including anti-miR-17 oligonucleotides (e.g., farabursen) and pharmacochaperones that rescue misfolded PC1 and restore trafficking in select PKD1 missense variants (e.g., VX-407)...Metabolic reprogramming is targeted by agents such as metformin, bempedoic acid, GLP-1 receptor agonists, and structured dietary interventions...Collectively, these advances signal a transition toward a layered, mechanism-guided framework in which vasopressin blockade is integrated with metabolic, other signaling, and genotype-specific therapies. As biomarkers and risk stratification tools mature, ADPKD management is poised to become increasingly precise, tolerable, and effective."

Journal • Autosomal Dominant Polycystic Kidney Disease • Gene Therapies • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • IGF1 • MIR17 • PKD1 • PRKD1

Uncovering the Red Flags: A Cross-Sectional Retrospective Case-Control Study on Predictors of Early Onset Colorectal Cancer in a Multi-State Community Health System. (PubMed, Cancer Prev Res (Phila)) - "Across all models, several predictors were significantly associated with higher EOCRC odds, including alcohol use history, higher number of comorbidities, abdominal pain, rectal bleeding, constipation, iron deficiency anemia, and prescriptions for metformin, non-steroidal inflammatory drugs, and multivitamins...By concurrently including symptoms, medical history, and sociodemographic characteristics, we constructed and validated well-fitting models with good discrimination that replicated and extended prior case-control research. To facilitate earlier screening and detection, these EOCRC risk factors can be used to identify patients who would benefit from screening earlier than 45 years of age."

Journal • Retrospective data • Colorectal Cancer • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Oncology • Pain • Solid Tumor

Inferior vena cava agenesis presenting as iliofemoral deep vein thrombosis in a 49-year-old male (ASH 2025) - "Case Presentation We present the case of a 49-year-old man with a past medical history of hypertension managed with losartan and impaired glucose tolerance treated with metformin...He was started on enoxaparin and later transitioned to rivaroxaban for outpatient anticoagulation...Conclusion This case underscores the diagnostic and therapeutic challenges in managing iliofemoral DVT due to IVC agenesis. Early identification and intervention can lead to favorable outcomes, particularly with the use of endovascular techniques and comprehensive follow-up."

Cardiovascular • CNS Disorders • Developmental Disorders • Hematological Disorders • Hypertension • Thrombosis • Venous Thromboembolism

Error-corrected sequencing to quantify clonal hematopoiesis in breast cancer survivors treated with metformin in a randomized, placebo controlled, prospective clinical trial (ASH 2025) - "CH can be identified in the vast majority of breast cancer survivors using highly sensitivesequencing techniques and is associated with age and history of cytotoxic therapy. The variation in CHVAF over a 6-month period is low and does not appear to be affected by treatment with standard dosesof metformin. This ancillary study demonstrates the utility of ECS for the detection and quantification ofCH over time."

Clinical • Breast Cancer • Hematological Malignancies • Obesity • Oncology • Solid Tumor • DNMT3A • PPM1D • TET2 • TP53

Serine/glycine starvation induces metabolic rewiring to uncover ATF4-driven therapeutic vulnerabilities in infant ALL (ASH 2025) - "An FDA-approved drug screencomparing S/G starved and non-starved cells revealed selective sensitivity to drugs targeting upstreampathways of ATF4 activation, such as Trazodone, Metformin and Rapamycin. This was supported by significant sensitivity of the cells to OxPhos inhibitors Metformin,Rotenone and Phenformin.In conclusion, S/G starved KMT2Ar cells rely on the ATF4-mediated ISR for survival. Therefore,repurposing drugs active upstream or downstream of ATF4 could open potential new, more effective, lesstoxic therapeutic windows in the treatment of infant leukaemia."

IO biomarker • Cardiomyopathy • Cardiovascular • Cognitive Disorders • Hematological Malignancies • Leukemia • Solid Tumor • AARS1 • ASNS • ATF4 • DDIT4 • KMT2A • MTHFD2 • SESN2 • SLC7A11 • TRIB3

Impact of metformin on the incidence of thrombotic events in older patients with polycythemia vera and essential thrombocythemia in the United States (ASH 2025) - "MET users without a prior history of thrombosis had a lowerthrombotic risk than MET non-users with DM (HR=0.80, 95% CI: 0.65-0.99; p=0.04). There was nosignificant association between MET use and thrombotic risk (HR=1.05, 95% CI: 0.83-1.32; p= 0.69) amongpts with DM and a prior history of thrombosis.ConclusionsOur study suggests that the use of MET reduces the risk of thrombosis in older pts with PV/ET and DM,with the protection being more pronounced among pts with severe DM and without prior history ofthrombotic events.Research supported by the ASH Minority Fellow Award."

Clinical • Cardiovascular • Diabetes • Essential Thrombocythemia • Hematological Disorders • Infectious Disease • Influenza • Metabolic Disorders • Myeloproliferative Neoplasm • Polycythemia Vera • Respiratory Diseases • Thrombocytosis • Thrombosis

Identification of dynamic markers for multiple myeloma in patients with MGUS and T2DM (ASH 2025) - "Prior studies have identified several risk/protective factors for MM, such asobesity (Chang, JNCI 2016), monoclonal (M)-protein level (Chang, CEBP 2019), and metformin use (Chang,Lancet Haematol 2015)... Machine learning, e.g., RF models can incorporate dynamic markers in risk predictionmodels. For patients with T2DM and MGUS, the identified top dynamic markers and T2DM medicationcan predict progression of MGUS to MM. These findings, if further validated in other populations anddatabases, can inform potential interventions to deter progression of MGUS to MM and manage DM invulnerable patient populations with MGUS and T2DM."

Clinical • Diabetes • Genetic Disorders • Hematological Malignancies • Metabolic Disorders • Monoclonal Gammopathy • Multiple Myeloma • Obesity • Type 2 Diabetes Mellitus • CEBPA

Peripheral blood plasma proteomics reveals dysregulated cholesterol transport and complement pathways in myeloproliferative neoplasms (ASH 2025) - "Metabolic abnormalities have been implicated in MPN pathophysiology and prognosis.Hypocholesterolemia, cachexia, and dyslipidemia correlate with reduced survival in MPN patients, statinuse is associated with improved outcomes, and metformin use is linked to reduced MPN incidence...Notably, cholesterol uptake bymacrophages enhances complement activation and atherogenesis, further supporting thepathobiological relevance of this axis. Our plasma proteomic analysis reveals a mechanistic link between impaired cholesterol transport andcomplement overactivation in MPNs, highlighting the metabolic-immune axis as a potential therapeutictarget in myeloid malignancies and aging."

Atherosclerosis • Cachexia • Chronic Myeloid Leukemia • Dyslipidemia • Essential Thrombocythemia • Hematological Malignancies • Leukemia • Metabolic Disorders • Myelofibrosis • Polycythemia Vera • Thrombocytosis • Thrombosis • APOA1 • APOB • APOE • C1QA • C1QB • CLU • PROS1 • SFTPD

The association between sglt-2 inhibitor use and progression from monoclonal gammopathy of undetermined significance to multiple myeloma in US veterans (ASH 2025) - "Covariatesincluded age, sex, race (Non-Hispanic Black [NHB], Non-Hispanic White [NHW], Other, and Unknown),MGUS subtype (IgG, IgA, or light-chain), M-protein category (e.g., ≥1.5 g/dL), BMI category (underweight,normal weight, overweight, obese), creatinine level (>1.5 mg/dL), anemia status based on ICD-9/10 codes,Charlson Comorbidity Index (CCI), HbA1c level (>7%), months from DM to MGUS (±6 months), MGUSdiagnosis year (2014-2019 vs 2020-2024), and DM medication use (i.e., metformin, insulin, glucagon-likepeptide-1 receptor agonist [GLP-1RA], sulfonylureas [SU], thiazolidinediones [TZDs], and dipeptidylpeptidase-4 inhibitor [DPP-4i]), all at MGUS diagnosis... In patients with DM and MGUS, SGLT-2i use was associated with a 35% reduced risk ofprogression to MM. Prospective studies are needed to evaluate whether SGLT-2i may play a role in MMprevention.B.S. and L.L., co–first; T.T. and S.H., co–senior authors."

Diabetes • Genetic Disorders • Hematological Malignancies • Monoclonal Gammopathy • Multiple Myeloma • Obesity

Association between monoclonal gammopathy of undetermined significance and cardiovascular disease risk among individuals with type 2 diabetes: A Taiwan nationwide Study (ASH 2025) - "Covariates included ages at T2D and MGUSdiagnosis, respectively, use of antidiabetic medications within 1 year before MGUS diagnosis (metformin,GLP-1 receptor agonists, SGLT2 inhibitors, insulin, and sulfonylureas), and the Charlson Comorbidityindex (CCI) within ±1 year of MGUS diagnosis... In this predominantly Asian population, the incidence of MGUS and CVD was highlycorrelated. Furthermore, consistent with evidence from western countries, MGUS is associated with anelevated risk of developing CVD. Both MGUS and CVD contribute to multimorbidity in individuals withT2D."

Clinical • Cardiovascular • Diabetes • Hematological Malignancies • Metabolic Disorders • Monoclonal Gammopathy • Type 2 Diabetes Mellitus

In vitro and In Vivo FOXO3 dependent induction of fetal hemoglobin (ASH 2025) - "Unfortunately, the only widely used therapy to induce HbF, hydroxyurea (HU), is clinically effectivein only half of adults with SCD...NBSGW mice were engrafted with 1E6 wild type HSCs per mouse by retro orbital injections following busulfan conditioning and fed on control (open std... Our study in erythroid culture confirmed the FOXO3 dependence of IGFBP3 mediated HbF induction as FOXO3 knockdown removes IGFBP3's ability to increase HbF levels in erythroid culture. This supports our proposed HbF induction model that IGFBP3 mediated HbF induction occurs by activation of FOXO3. We showed that the NBSGW mouse model engrafted with human HSCs can serve as an excellent model for testing drug induction of HbF in vivo."

Preclinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • CD34 • FOXO3 • IGFBP3 • PTPRC

Glucose transporter 5 enhances CAR-T cell metabolic function and serial killing (ASH 2025) - P1 | "In a subset ofpatients Glut1 is high (SLC2A1) and these tumor cells do not express high levels of GAPDH or LDHA.These data suggest that the complete oxidation of glucose in the mitochondria maybe supporting thegrowth of AML blasts; positioning the complex 1 inhibitor metformin as an important candidate alongwith standard therapy...Expressing glucose transporters to optimize fuelselection, expedite ATP replenishment, support cytokine production, and bolster anti-tumour functionhas been fraught with challenges. Here, we show that GLUT5 is an ideal candidate with immediatetranslational relevance, including CAR-Ts against AML."

CAR T-Cell Therapy • IO biomarker • CD123 • CD33 • CD34 • GAPDH • IL2 • IL3RA • LDHA • PTPRC • SLC2A1

GLP‑1 receptor agonists and clonal hematopoiesis: Early human signals of anti‑inflammatory clone mitigation and lower MDS‑to‑AML progression (ASH 2025) - "To correlate thesefinding to GLP-1RA therapy, we also compared for patients on metformin to rule-out diabetes control asimproving clonal burden...doi:10.1177/20420188231222367. PMID: 38288136; PMCID: PMC10823863."

Acute Myelogenous Leukemia • Complement-mediated Rare Disorders • Diabetes • Hematological Malignancies • Immune Modulation • Immunology • Metabolic Disorders • Myelodysplastic Syndrome • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • BCORL1 • CALR • DNMT3A • IL1B • JAK2 • NLRP3 • TNFA

Impact of metformin on outcomes in older adults with classical myeloproliferative neoplasms (ASH 2025) - No abstract available

Clinical • Myeloproliferative Neoplasm

P111 A multicentre service evaluation highlighting the variable off-label prescribing practice of spironolactone in the management of hidradenitis suppurativa: the need for evidence-based guidelines. (PubMed, Br J Dermatol) - "Most were prescribed spironolactone as an adjunct to their existing management, including oral antibiotics, metformin and adalimumab. We conclude that there is significant variability in patient selection, monitoring and prescribing practices of spironolactone for HS across these UK sites. With a view to addressing the uncertainties outlined in the James Lind Priority Setting Partnerships for HS, we propose that a multicentre randomized controlled trial is needed to inform the evidence base and to produce clear UK guidelines on treatment with spironolactone in HS."

Journal • Retrospective data • Dermatology • Hidradenitis Suppurativa • Immunology • Inflammation • Pain • Xerostomia

P121 Treatment with semaglutide improves the systemic inflammatory burden associated with hidradenitis suppurativa. (PubMed, Br J Dermatol) - "The majority of patients (n = 54) had Hurley stage II disease, with 10 patients classified as Hurley stage III and 5 as Hurley stage I. Twenty-two patients were established on adalimumab with two on infliximab. Other biologics prescribed alongside semaglutide included brodalumab (n = 8) and secukinumab (n = 1). Nineteen patients were coprescribed metformin, and for 16 patients rescue antibiotics including rifampicin and clindamycin...Semaglutide can improve not only metabolic control, weight, flare frequency and quality of life, but also systemic inflammation and thus health outcomes (Lyons et al.). Although our findings did not reach statistical significance, the consistent trends observed in inflammatory markers and the established efficacy of semaglutide in weight loss and metabolic improvement suggest that it can enhance health outcomes for this patient population."

Journal • Retrospective data • Dermatology • Genetic Disorders • Hidradenitis Suppurativa • Immunology • Inflammation • Metabolic Disorders • Obesity • Systemic Inflammatory Response Syndrome

Combination metformin and liraglutide in PCOS: clinical efficacy in women and preclinical insights from gut microbiome modulation in rats. (PubMed, Front Endocrinol (Lausanne)) - "In a separate animal study, female Sprague-Dawley rats were divided into five groups: (1) PCOS model group (letrozole 1 mg/kg orally); (2) MET group (letrozole + metformin 200 mg/kg orally); (3) LIRA group (letrozole + liraglutide 0.2 mg/kg subcutaneously); (4) COM group (letrozole + metformin + liraglutide at above doses); and (5) healthy controls (no treatment). Metformin combined with liraglutide significantly improved metabolic and endocrine characteristics in PCOS women. The associated amelioration of gut microbiota dysbiosis in PCOS rats suggests a potential mechanistic link, which warrants verification in future clinical studies."

Clinical • Journal • Preclinical • Gastrointestinal Disorder • Obesity • Polycystic Ovary Syndrome

Beta cells to brain cells: The pivotal role of insulin and glucose metabolism in Alzheimer's disease. (PubMed, Neuroprotection) - "Choice of antidiabetes therapy is imperative: evidence supports the use of metformin, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide-1 receptor analogs, and sodium glucose cotransporter 2 inhibitors to help prevent and mitigate cognitive outcomes and AD...We are at a fascinating juncture: preclinical research is at a stage to inform the development of rational previously unexplored targets. Simultaneously, current clinical evidence is translatable now into real-world strategies to reduce the incidence and severity of comorbid AD in our aging population."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

BC06 Investigating the role of metformin in melasma management: a review. (PubMed, Br J Dermatol) - "Combination treatments with topical agents, such as hydroquinone, retinoids and Kligman's formula, showed increased efficacy over both monotherapy and placebo treatments. Further large-scale, double-blinded trials are required to define optimal dosing, treatment duration and long-term efficacy. This review emphasizes the need for future research into repurposing systemic agents for dermatological conditions and highlights the importance of personalized patient care strategies in the management of melasma."

Journal • Review • Aesthetic Medicine • Dermatology • Dermatopathology

CCMR Two: A Phase IIa, Randomised, Double-blind, Placebo-controlled Trial of the Ability of the Combination of Metformin and Clemastine to Promote Remyelination in People With Relapsing-remitting Multiple Sclerosis Already on Disease-modifying Therapy (clinicaltrials.gov) - P2 | N=70 | Completed | Sponsor: Cambridge University Hospitals NHS Foundation Trust | Active, not recruiting ➔ Completed | Trial completion date: May 2025 ➔ Sep 2025

Trial completion • Trial completion date • CNS Disorders • Multiple Sclerosis

From metabolic modulator to precision-oncology adjunct: Mechanistic insights and biomarker strategies for metformin in colorectal cancer (ESMO Asia 2025) - "Metformin's paradoxical outcomes in CRC highlight the need for biomarker-guided, population-specific trials. Integrating molecular and immune profiling could reposition metformin as a precision-oncology adjunct, bridging metabolic control with targeted cancer therapeutics."

Biomarker • Colorectal Cancer • Oncology • Solid Tumor • NLRP3