The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Metformin Action: Concentrations Matter
Open accessAbstract
Metformin has been used for nearly a century and is now the most widely prescribed oral anti-diabetic agent worldwide. Yet how metformin acts remains only partially understood and controversial. One key reason may be that almost all previous studies were conducted with supra-pharmacological concentrations (doses) of metformin, 10-100 times higher than maximally achievable therapeutic concentrations found in patients with type 2 diabetes mellitus.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“activation of AMPK by metformin has been observed at much lower metformin concentrations in comparable cell culture protocols using metformin concentrations that are within the upper limits of its therapeutic plasma levels (4, 134).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [4]
In the citing paper
“In both studies, Arunachalam et al. (110) and Ghosh et al. (111) used 50 μM metformin and justified this concentration on the basis that estimates of metformin levels in the portal circulation following oral absorption are between 40 and 70 μM (4, 181).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [4]
Citations
Cites
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652
The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
Shaw, R. J., Lamia, K. A., Vasquez, D., Koo, S.-H., Bardeesy, N., DePinho, R. A., Montminy, M., & Cantley, L. C. (2005) · Science · doi:10.1126/science.1120781 · Cited by 1,950
El-Mir, M.-Y., Nogueira, V., Fontaine, E., Avéret, N., Rigoulet, M., & Leverve, X. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.1.223 · Cited by 1,399
Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase
Madiraju, A. K., Erion, D. M., Rahimi, Y., Zhang, X.-M., Braddock, D. T., Albright, R. A., Prigaro, B. J., Wood, J. L., Bhanot, S., MacDonald, M. J., et al. (2014) · Nature · doi:10.1038/nature13270 · Cited by 1,284
Foretz, M., Hébrard, S., Leclerc, J., Zarrinpashneh, E., Soty, M., Mithieux, G., Sakamoto, K., Andreelli, F., & Viollet, B. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40671 · Cited by 1,181
Metabolic effects of metformin in non-insulin-dependent diabetes mellitus
Stumvoll, M., Nurjhan, N., Perriello, G., Dailey, G., & Gerich, J. E. (1995) · New England Journal of Medicine · doi:10.1056/nejm199508313330903 · Cited by 1,148
Fullerton, M. D., Galic, S., Marcinko, K., Sikkema, S., Pulinilkunnil, T., Chen, Z.-P., O'Neill, H. M., Ford, R. J., Palanivel, R., O'Brien, M., et al. (2013) · Nature Medicine · doi:10.1038/nm.3372 · Cited by 893
Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP
Miller, R., Chu, Q., Xie, J., Foretz, M., Viollet, B., & Birnbaum, M. J. (2013) · Nature · doi:10.1038/nature11808 · Cited by 845
Use of Cells Expressing γ Subunit Variants to Identify Diverse Mechanisms of AMPK Activation
Hawley, S. A., Ross, F. A., Chevtzoff, C., Green, K. A., Evans, A., Fogarty, S., Towler, M. C., Brown, L. J., Ogunbayo, O. A., Evans, A. M., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.04.001 · Cited by 773
Metformin pathways: pharmacokinetics and pharmacodynamics
Gong, L., Goswami, S., Giacomini, K. M., Altman, R. B., & Klein, T. E. (2012) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e3283559b22 · Cited by 495
Cited by
Sorted by citations
Items 401–448 of 448
The enhancement of CRISPR/Cas9 gene editing using metformin
Rollins, J. L., Hall, R. M., Lemus, C. J., Leisten, L. A., & Johnston, J. M. (2023) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2023.101539
Anti-cancer Efficacy of Metformin: Recent Updates on Breast and Other Cancers
Kabir, M. I., Kumar, R., Bugata, L. S. P., & Raina, K. (2023) · Current Pharmacology Reports · doi:10.1007/s40495-023-00336-w
Adam, J., Harada, M., Covic, M., Brandmaier, S., Muschet, C., Huang, J., Han, S., Ge, J., Rommel, M., Rotter, M., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-3931333/v1
أدريس, ع., عزاقة, إ., & عبدالله, ف. (2024) · Journal of Pure & Applied Sciences · doi:10.51984/jopas.v23i1.2389
Sokolova, A. M., PUSHKAREV, V. V., SOKOLOVA, L. K., Pushkarev, V. M., & Tronko, M. D. (2024) · INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine) · doi:10.22141/2224-0721.20.3.2024.1391
Williams, K. J. (2024) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2024.118530
Bacterial targets of fecal host miRNAs in high-fat diet-fed mice
Silamiķele, L., Silamiķelis, I., Kotoviča, P. P., & Kloviņš, J. (2025) · PLoS ONE · doi:10.1371/journal.pone.0315871
Heightened sensitivity to adverse effects of metformin in mtDNA mutant patient cells
Ryytty, S., Nurminen, K., Mäkinen, P. I., Suomalainen, A., & Hämäläinen, R. H. (2025) · Life Sciences · doi:10.1016/j.lfs.2025.123486
Bhati, F. K., Saha, U., Singh, S., & Bhat, M. K. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.29.656565
Svirskienė, N., Svirskis, G., Jankevičiūtė, S., & Borutaitė, V. (2025) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2025.110494
Wu, T., Horowitz, M., Jones, K. L., & Rayner, C. K. (2025) · Molecular Metabolism · doi:10.1016/j.molmet.2025.102276
Frías-Anaya, E., Gallego-Gutiérrez, H., Bui, C., Birrueta, J. O., Steinberg, J. D., Niesman, I. R., Gongol, B., Nguyen, B., Sawhney, A., Mizushima, Z., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.08.693036 · Cited by 1
Karademir, D., Todorova, V., Ebner, L. J. A., Samardzija, M., & Grimm, C. (2022) · Figshare · doi:10.6084/m9.figshare.19588644
Karademir, D., Todorova, V., Ebner, L. J. A., Samardzija, M., & Grimm, C. (2022) · Figshare · doi:10.6084/m9.figshare.19588632
Zhang, Y.-L., Liu, F., Li, Z.-B., He, X.-T., Li, X., Wu, R.-X., Sun, H.-H., Ge, S.-H., Chen, F.-M., & An, Y. (2022) · Figshare · doi:10.6084/m9.figshare.20329581
Luo, Z., Wang, B., Luo, F., Guo, Y., Jiang, N., Wei, J., Wang, X., Tseng, Y., Chen, J., Zhao, B., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24089216
Pěnčík, J., Philippe, C., Schlederer, M., Atas, E., Pecoraro, M., Grund‐Gröschke, S., Li, W., Tracz, A., Heidegger, I., Lagger, S., et al. (2023) · Figshare · doi:10.6084/m9.figshare.23937289
Karademir, D., Todorova, V., Ebner, L. J. A., Samardzija, M., & Grimm, C. (2022) · Figshare · doi:10.6084/m9.figshare.19588620
Karademir, D., Todorova, V., Ebner, L. J. A., Samardzija, M., & Grimm, C. (2022) · Figshare · doi:10.6084/m9.figshare.19588629
Karademir, D., Todorova, V., Ebner, L. J. A., Samardzija, M., & Grimm, C. (2022) · Figshare · doi:10.6084/m9.figshare.19588641
Karademir, D., Todorova, V., Ebner, L. J. A., Samardzija, M., & Grimm, C. (2022) · Figshare · doi:10.6084/m9.figshare.19588626
Additional file 1 of Loss of hexokinase 1 sensitizes ovarian cancer to high-dose metformin
Šimčíková, D., Gardáš, D., Hložková, K., Hruda, M., Žáček, P., Rob, L., & Heneberg, P. (2021) · Figshare · doi:10.6084/m9.figshare.17163368
Zhu, X., Shen, J., Feng, S., Huang, C., Wang, H., Huo, F., & Liu, H. (2023) · Figshare · doi:10.6084/m9.figshare.23265023
Zhang, Y.-L., Liu, F., Li, Z.-B., He, X.-T., Li, X., Wu, R.-X., Sun, H.-H., Ge, S.-H., Chen, F.-M., & An, Y. (2022) · Figshare · doi:10.6084/m9.figshare.20329578
Luo, Z., Wang, B., Luo, F., Guo, Y., Jiang, N., Wei, J., Wang, X., Tseng, Y., Chen, J., Zhao, B., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24089219
Harada, M., Adam, J., Covic, M., Ge, J., Brandmaier, S., Muschet, C., Huang, J., Han, S., Rommel, M., Rotter, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26027587
Zhang, Y.-L., Liu, F., Li, Z.-B., He, X.-T., Li, X., Wu, R.-X., Sun, H.-H., Ge, S.-H., Chen, F.-M., & An, Y. (2022) · Figshare · doi:10.6084/m9.figshare.20329575
Singh, A., Gu, J. J., Zhang, Q., Torka, P., Sundaram, S., Mavis, C. K., & Hernandez‐Ilizaliturri, F. J. (2020) · Figshare · doi:10.6084/m9.figshare.12612613
Relationship between breast cancer and metformin: A bibliometric review
Wang, Z., Zhao, F., & Wang, L. (2026) · Medicine · doi:10.1097/md.0000000000047868
Kurelac, I., Cavina, B., Nanetti, F., Corra, S., Sollazzo, M., Coadǎ, C. A., Grillini, M., Scalambra, L., Lama, E., Angi, E., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.28.708681
Koshy, R. R., Kumar, A. A., Maliyil, B. T., Regie, R., Jairaj, S., & Satish, M. T. (2026) · Middle East Fertility Society Journal · doi:10.1186/s43043-026-00316-2
Metformin & Chronic Kidney Disease (CKD) : a reassessment of the benefit/risk ratio
Kajbaf, F. (2015) · theses.fr (ABES) · doi:10.70675/7a26b581z94ddz4e2fz9a48z97f6f7d8354a
Predicting stress-induced vulnerability to depression in diabetes
Alaeddine, L. M. (2022) · theses.fr (ABES) · doi:10.70675/41d9cd78zd5dez4ccfzae36zbb176db78e3f
İtil, E., Surer, S. I., Hızlıateş̨, C. G., & Oktay, G. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-12042-z
Ramadhan, M. B., Hakim, M. H., Suskhan, M. N., & Cahyanur, R. (2026) · South Asian Journal of Cancer · doi:10.25259/sajc_11_2025
Szeremeta, Y. C., Barros, W. D. M., Dezanetti, T., de Oliveira, V. E., Amaral, P. A. H., Ferreira, J. B., Cunha, M. P., Guiard, B. P., & Moreira, E. L. G. (2026) · PharmaNutrition · doi:10.1016/j.phanu.2026.100510
Jouabadi, S. M., Jüttner, A. A., Claringbould, A., VRIES, R. D., Garrelds, I. M., Musterd‐Bhaggoe, U. M., Stricker, B. H. C., Kavousi, M., Danser, A. H. J., Ahmadizar, F., et al. (2026) · British Journal of Pharmacology · doi:10.1111/bph.70533 · Cited by 1
Lei, D., Wu, J.-H., Zeng, X.-H., Xu, R., Zheng, S.-S., Zhu, X.-J., & Jian-a, Y. (2026) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2026.05.024
He, C., Wesselink, M., Huijts, J. Y., Zhong, Z., Eggelbusch, M., Jaspers, R. T., & Wüst, R. C. I. (2026) · The FASEB Journal · doi:10.1096/fj.202600077rrr
НЕЙРОПРОТЕКТОРНЫЕ ФУНКЦИИ МЕТФОРМИНА (ОБЗОР ЛИТЕРАТУРЫ)
Гридасова, Е. И., Плешкова, В. С., Чичкан, А. С., & Смирнова, П. Н. (2026) · Military and tactical medicine Emergency medicine · doi:10.55359/2782-3296.2026.81.44.009
Metformin triggers ATF4-mediated UPRmt and COX-2 inflammation in adipocytes
Poothong, J., Chiamkunakorn, C., Suthammarak, W., Phanaksri, T., Auewarakul, P., Yong, J., & Kaufman, R. J. (2026) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2026.120191
The coordinated actions of metformin in the intestine and liver improves hyperglycemia
He, L., An, H., Ramirez, K., Radovick, S., & Wondisford, F. E. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117791 · Cited by 1
Kowalik, A., Paszenda, P., Frątczak, A., Piwowar, A., Obrycka, P., Dudek, M., & Woźniak, S. (2026) · Tissue and Cell · doi:10.1016/j.tice.2026.103873
Zhang, K., Chen, Y., Ran, L., Tong, W., Dai, L., Yang, Z., Chen, Q., Zheng, J., & Hu, G. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1857676
Metformin Attenuates the High-Glucose Effect on MORG1 Expression in HEK293 Cells
Bondeva, T., Reuter, S., Westphal, A., Mrowka, R., & Wolf, G. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48090934
Wang, G., Zhao, Y., Liu, G., Du, Y., Liu, S., Yang, Y., Bu, S., & Zhao, B. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198451
Jang, S., Kim, S., Kim, G., Hong, J., Park, I., & Jin, H. (2026) · Pharmacology Research & Perspectives · doi:10.1002/prp2.70330
Metadata
- Authors
- He, L., & Wondisford, F. E.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Wondisford, Fredric E.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 21
- Issue
- 2
- Pages
- 159-162
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2080654617
- Cited by
- 448
- References
- 18
- Citations by year
- 2026: 25 · 2025: 30 · 2024: 39 · 2023: 43 · 2022: 61 · 2021: 57 · 2020: 59 · 2019: 37 · 2018: 41 · 2017: 30 · 2016: 16 · 2015: 10
- FWCI
- 14.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Keywords
- metformin, type 2 diabetes, mechanism of action, therapeutic drug concentrations, oral antidiabetic drugs, pharmacokinetics
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Humans, Metformin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review