Metformin †Rx
Rx metabolic modulator: AMPK ↑, mTOR/IGF ↓, CSC ↓; strong epi/trial data for risk reduction in breast/colorectal/prostate/pancreatic.
Forms: Immediate-release tablets (500-1000 mg) · Extended-release tablets (500-750 mg)
Key Takeaway
Metabolic reprogrammer that activates AMPK, suppresses mTOR/insulin-IGF signaling, and targets cancer stem-cell phenotypes; broad human data (esp. in diabetics) show risk-reduction and outcome signals.
Evidence at a glance
Hundreds of epi studies + 50+ RCTs/meta; consistent risk reduction (OR 0.7-0.8); adjunct PFS/OS signals in breast (NCIC MA.32), prostate (MA.03); ongoing trials in pancreas/lung.
How it may work
Metformin lowers hepatic gluconeogenesis and circulating insulin/IGF-1, activating AMPK (↑AMP:ATP) and inhibiting mTORC1 (via TSC2/Rheb). Tumor-intrinsic effects include decreased protein synthesis, cell-cycle arrest, and CSC downshift (ALDH⁺/CD44⁺↓). It can sensitize tumors to chemo/radiation and may reduce recurrence risk in select cohorts.
Targets & pathways
Curated mechanistic targets reported for this agent — how it may act on cells, not proof of a clinical effect.
Often studied / combined with
Combinations reported in the literature, not a protocol or a recommendation.
- Doxorubicin: Improved response and reduced cardiotoxicity in breast cancer.
- Curcumin: Amplified AMPK/mTOR effects in lung models.
- Resveratrol: Cooperative IGF/mTOR inhibition in colorectal cancer.
- Quercetin: Enhanced CSC targeting in prostate preclinical.
Overlapping mechanisms
- mTOR: Overlaps with rapalogs/metabolic agents; GI cumulative.
- AMPK: Redundant with salicylates/berberine; monitor glucose.
Safety & interactions
Severity and how well-established each signal is are shown separately. Verify everything with your oncologist or pharmacist — absence here does not mean safe.
Timing
- With-meal: Minimizes GI side effects.
- BID: Divided for steady glucose control.
References
- PMC5270304: Metformin in cancer prevention and treatment
- PMC10286395: AMPK/mTOR mechanisms in oncology
- PMC5772929: CSC modulation by metformin
- PMC4200664: Insulin/IGF-1 reduction and cancer risk
- DOI 10.3390/nu13082654: Synergy with doxorubicin in breast models
- PMC10221542: Combination with curcumin in lung cancer
Research
No published studies for Metformin yet
New studies appear here once they’ve been reviewed. Browse all studies.
Dose: as studied, not a recommendation
Ranges seen in adjunct / practice use: 500–2000 mg/day (po) divided BID; with meals, Diabetes standard 1000-2000 mg/day; oncology adjunct 500-1000 mg BID; ER form for GI tolerance; renal dosing critical..
Clinical trials studying Metformin †Rx
3 ongoing · 8 completed · tracked from ClinicalTrials.gov. Recruiting is not the same as proven, and completed is not the same as positive — read the results. Not a recommendation.
- Study of Metformin With Carboplatin/Paclitaxel Chemotherapy in Patients With Advanced Ovarian Cancer
- A Phase II, Single-Arm Study of RAD001 (Everolimus), Letrozole, and Metformin in Patients With Advanced or Recurrent Endometrial CarcinomaPrimary outcome measured: Clinical Benefit (CBR) Complete Response + Partial Response + Stable Disease Rates) Based on RECIST v1.1.
- Metformin and Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal CancerPrimary outcome measured: Progression Free Survival (PFS)
- Comparison of the Effectiveness Metformin for Deceasing Proliferative Marker in Endometrial Cancer Cells
- IMPACT: A Randomized WOO Study of Novel Therapeutic Agents in Women Triaged to Primary Surgery for EOC
- Effects of Cyproterone Compound-spironolactone, Metformin and Pioglitazone on Inflammatory Markers in PCOS
- Myoinositol Treatment and Asprosin Levels in PCOS
- The Effect of GLP-1 Agonists Versus OCs on Reproductive Disorders and Cardiovascular Risks in Overweight PCOSPrimary outcome measured: Assessment of Reproductive FunctionsResults on ClinicalTrials.gov →Results paper (PMID 28646699) →Results paper (PMID 12046553) →Results paper (PMID 24389146) →Results paper (PMID 26426951) →Results paper (PMID 14688154) →Results paper (PMID 22777527) →Results paper (PMID 20471009) →Results paper (PMID 29569621) →Results paper (PMID 28463030) →Results paper (PMID 28860713) →Results paper (PMID 30459598) →Results paper (PMID 37653215) →
5 stopped (terminated / withdrawn / suspended)
- Metformin Hydrochloride and Doxycycline in Treating Patients With Localized Breast or Uterine Cancer · Terminated
- Study of Metformin Plus Oligomeric Procyanidin Complex for Pharmacologic Manipulation of AGE (Advanced Glycation Endproducts) Levels in Prostate Cancer Patients · Withdrawn
- Pilot Study of Metformin in HNSCC to Investigate the Effects of MF, Tumor Genotype and MF-genotype Interactions, on Tumor Metabolism and Anoikis · Terminated
- Metformin Hydrochloride in Treating Patients With Pancreatic Cancer That Can be Removed by Surgery · Withdrawn
- Metformin Hydrochloride, Carboplatin, and Paclitaxel in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer · Withdrawn
Appears in these protocol claims
Metformin †Rx is named in these protocols discussed online. Listed for transparency: being part of a protocol is not evidence that it works, and OncoForge does not endorse them.
- Ivermectin / Benzimidazole Protocol Claims : Aggressive online protocols combining ivermectin with fenbendazole or mebendazole.
- Jane McLelland / Metabolic Blocking Claims : Multi-pathway metabolic strategy based around starving cancer fuel routes and blocking escape pathways.
- Care Oncology-Style Repurposed Drug Claims : Clinic-associated repurposed-drug approach often discussed around four common medications.
- Fasting-Mimicking Diet / Ketogenic / Press-Pulse Claims : Metabolic approaches focused on glucose, insulin, ketones, fasting stress, and treatment sensitivity.