Back to resultsMetformin Pharmacology in Human Cancers: A Proof of Principle Study
Primary Purpose
Thoracic Neoplasm
Status
Terminated
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Metformin
Sponsored by
About this trial
This is an interventional basic science trial for Thoracic Neoplasm
Eligibility Criteria
Inclusion Criteria:
- Invasive malignant solid tumor of thoracic origin (e.g., lung, esophageal, thymus, mesothelioma, chest wall, mediastinum, trachea, pleura) with the intent to treat or biopsy by surgery as standard of care. Tumor must be ≥2 centimeters (cm).
- Patients with multicentric disease are eligible. Samples from all available tumors are requested for research purposes.
- Patients with Type 2 diabetes mellitus being treated with metformin (any dose) for a clinical indication at the time of study enrollment are eligible, and will continue metformin treatment as clinically indicated during the presurgical study period. Their dose of metformin will NOT be changed.
- Patients not on metformin at the time of study entry must be willing to take metformin extended release (Glucophage® XR, 750 mg QD for 4 days, then 750 mg BID for 3-6 days) for a total of 7-10 days prior to surgery.
- Patients do not require a diagnosis of diabetes to be enrolled in the study.
- All patients must be willing to keep a drug diary indicating the dates and times of metformin administration.
Patients must meet the following clinical laboratory criteria:
- Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3 and platelet count greater than or equal to 75,000/mm3.
- Total bilirubin less than or equal to 1.5x the upper limit of the normal range (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3x ULN.
- Estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73m2 or estimated creatinine clearance (eCrCL) > 60 mL/min
- Ability to give informed consent.
- Patients must be willing to provide 20 milliliters (mL) of blood for research use.
- Patient must be willing to provide consent for use of archived tissue for research.
Exclusion Criteria:
- History of diabetes that is currently being treated without metformin.
- Patients who, at the time of study entry, are not taking metformin for a clinical indication, and who will need a radiographic analysis with an iodinated contrast agent during the metformin study treatment period.
- This criterion does not apply to patients taking clinically indicated metformin at the time of study entry.
- History of liver disease as defined with liver function tests (LFTs) above those in the inclusion
- Known hypersensitivity to metformin.
- History of reactive hypoglycemia.
- Active or history of lactic acidosis, metabolic acidosis, or diabetic ketoacidosis.
Sites / Locations
- Dartmouth Hitchcock Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Metformin
Arm Description
Patients enrolled will be treated with metformin (administered orally; 750 mg QD for 4 days, then 750 mg BID for 3-6 days; or clinically indicated metformin) for a total of 7-10 days prior to surgery, up until the night before surgery.
Outcomes
Primary Outcome Measures
Lung Tumor Tissue Concentration of Metformin
To determine the intra-tumor concentrations of metformin, with a standard deviation ≤25% of the mean, in patients with solid tumors of thoracic origin administered metformin extended release.
Secondary Outcome Measures
Concentration of Metformin in Adipose Tissue
To determine the concentration of metformin in adipose tissue.
Concentration of Metformin in Tumor-adjacent Normal Tissue
To determine the concentration of metformin in tumor-adjacent normal tissue.
Concentration of Metformin in Plasma.
To determine the concentration of metformin in plasma.
Concentration of Metformin in Whole Blood.
To determine the concentration of metformin in whole blood.
Full Information
NCT ID
NCT03477162
First Posted
March 14, 2018
Last Updated
November 30, 2022
Sponsor
Dartmouth-Hitchcock Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03477162
Brief Title
Metformin Pharmacology in Human Cancers: A Proof of Principle Study
Official Title
Metformin Pharmacology in Human Cancers
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Terminated
Why Stopped
Enrollment was closed as efforts had become more challenging, and the lab indicated that they were able to obtain their primary objective with the number that had already been enrolled.
Study Start Date
May 15, 2018 (Actual)
Primary Completion Date
November 30, 2021 (Actual)
Study Completion Date
November 30, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dartmouth-Hitchcock Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a presurgical (proof of principle, window of opportunity) study in patients with surgically resectable thoracic tumors to determine steady-state tissue and plasma concentrations of metformin.
Detailed Description
To understand the variability in clinical results testing metformin as an anti-cancer agent, it is important to determine the concentrations of metformin that are achievable in tissue. Clinical effects of metformin develop gradually over several days of treatment. Steady-state plasma metformin concentrations are correlated with anti-hyperglycemic response. Thus, achieving steady-state concentrations in this study will allow accurate determination of the most representative concentrations of metformin in normal and cancerous tissues, as well as determine AMP-activated protein kinase (AMPK) signaling differences in these tissues. As tha Primary Objective is to determine the concentration of metformin in tumors, patients will be treated with metformin extended release (ER) (Glucophage® XR), starting at 750 milligrams (mg) oral (PO) once daily (QD) for 4 days, then escalating to 750 mg PO twice daily (BID) for 3-6 days prior to surgery. FDA prescribing information indicates that metformin reaches steady-state plasma concentrations within 24-48 hours after the start of dosing in humans; thus, the 7-to-10-day time frame of this study will allow sufficient time for metformin to reach steady-state plasma concentrations, in addition to time allotted for potential accumulation in tissues. Metformin concentrations will be measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) assay.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thoracic Neoplasm
7. Study Design
Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Metformin
Arm Type
Experimental
Arm Description
Patients enrolled will be treated with metformin (administered orally; 750 mg QD for 4 days, then 750 mg BID for 3-6 days; or clinically indicated metformin) for a total of 7-10 days prior to surgery, up until the night before surgery.
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
Metformin will be given to patients prior to surgery.
Primary Outcome Measure Information:
Title
Lung Tumor Tissue Concentration of Metformin
Description
To determine the intra-tumor concentrations of metformin, with a standard deviation ≤25% of the mean, in patients with solid tumors of thoracic origin administered metformin extended release.
Time Frame
Within 7 days from surgery
Secondary Outcome Measure Information:
Title
Concentration of Metformin in Adipose Tissue
Description
To determine the concentration of metformin in adipose tissue.
Time Frame
Within 7 days from surgery
Title
Concentration of Metformin in Tumor-adjacent Normal Tissue
Description
To determine the concentration of metformin in tumor-adjacent normal tissue.
Time Frame
Within 7 days from surgery
Title
Concentration of Metformin in Plasma.
Description
To determine the concentration of metformin in plasma.
Time Frame
Within 7 days from surgery
Title
Concentration of Metformin in Whole Blood.
Description
To determine the concentration of metformin in whole blood.
Time Frame
Within 7 days from surgery
Other Pre-specified Outcome Measures:
Title
AMPK Activity Alterations.
Description
To determine whether metformin alters AMPK activity in tumor cells.
Time Frame
Within 7 days from surgery.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Invasive malignant solid tumor of thoracic origin (e.g., lung, esophageal, thymus, mesothelioma, chest wall, mediastinum, trachea, pleura) with the intent to treat or biopsy by surgery as standard of care. Tumor must be ≥2 centimeters (cm).
Patients with multicentric disease are eligible. Samples from all available tumors are requested for research purposes.
Patients with Type 2 diabetes mellitus being treated with metformin (any dose) for a clinical indication at the time of study enrollment are eligible, and will continue metformin treatment as clinically indicated during the presurgical study period. Their dose of metformin will NOT be changed.
Patients not on metformin at the time of study entry must be willing to take metformin extended release (Glucophage® XR, 750 mg QD for 4 days, then 750 mg BID for 3-6 days) for a total of 7-10 days prior to surgery.
Patients do not require a diagnosis of diabetes to be enrolled in the study.
All patients must be willing to keep a drug diary indicating the dates and times of metformin administration.
Patients must meet the following clinical laboratory criteria:
Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3 and platelet count greater than or equal to 75,000/mm3.
Total bilirubin less than or equal to 1.5x the upper limit of the normal range (ULN).
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3x ULN.
Estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73m2 or estimated creatinine clearance (eCrCL) > 60 mL/min
Ability to give informed consent.
Patients must be willing to provide 20 milliliters (mL) of blood for research use.
Patient must be willing to provide consent for use of archived tissue for research.
Exclusion Criteria:
History of diabetes that is currently being treated without metformin.
Patients who, at the time of study entry, are not taking metformin for a clinical indication, and who will need a radiographic analysis with an iodinated contrast agent during the metformin study treatment period.
This criterion does not apply to patients taking clinically indicated metformin at the time of study entry.
History of liver disease as defined with liver function tests (LFTs) above those in the inclusion
Known hypersensitivity to metformin.
History of reactive hypoglycemia.
Active or history of lactic acidosis, metabolic acidosis, or diabetic ketoacidosis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph Phillips, MD
Organizational Affiliation
Dartmouth-Hitchcock Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
18945920
Citation
Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009 Jan;32(1):193-203. doi: 10.2337/dc08-9025. Epub 2008 Oct 22.
Results Reference
background
PubMed Identifier
11602616
Citation
Witters LA. The blooming of the French lilac. J Clin Invest. 2001 Oct;108(8):1105-7. doi: 10.1172/JCI14178. No abstract available.
Results Reference
background
PubMed Identifier
22117616
Citation
Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). 2012 Mar;122(6):253-70. doi: 10.1042/CS20110386.
Results Reference
background
PubMed Identifier
23835523
Citation
Rena G, Pearson ER, Sakamoto K. Molecular mechanism of action of metformin: old or new insights? Diabetologia. 2013 Sep;56(9):1898-906. doi: 10.1007/s00125-013-2991-0. Epub 2013 Jul 9.
Results Reference
background
PubMed Identifier
11602624
Citation
Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001 Oct;108(8):1167-74. doi: 10.1172/JCI13505.
Results Reference
background
PubMed Identifier
12629126
Citation
Gunton JE, Delhanty PJ, Takahashi S, Baxter RC. Metformin rapidly increases insulin receptor activation in human liver and signals preferentially through insulin-receptor substrate-2. J Clin Endocrinol Metab. 2003 Mar;88(3):1323-32. doi: 10.1210/jc.2002-021394. Erratum In: J Clin Endocrinol Metab. 2004 Jan;89(1):434.
Results Reference
background
PubMed Identifier
10617608
Citation
El-Mir MY, Nogueira V, Fontaine E, Averet N, Rigoulet M, Leverve X. Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem. 2000 Jan 7;275(1):223-8. doi: 10.1074/jbc.275.1.223.
Results Reference
background
PubMed Identifier
7623902
Citation
DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med. 1995 Aug 31;333(9):541-9. doi: 10.1056/NEJM199508313330902.
Results Reference
background
PubMed Identifier
9742977
Citation
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):854-65. Erratum In: Lancet 1998 Nov 7;352(9139):1558.
Results Reference
background
PubMed Identifier
14623620
Citation
Hurst RT, Lee RW. Increased incidence of coronary atherosclerosis in type 2 diabetes mellitus: mechanisms and management. Ann Intern Med. 2003 Nov 18;139(10):824-34. doi: 10.7326/0003-4819-139-10-200311180-00010.
Results Reference
background
PubMed Identifier
21241070
Citation
Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK, Furlong TJ, Greenfield JR, Greenup LC, Kirkpatrick CM, Ray JE, Timmins P, Williams KM. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 2011 Feb;50(2):81-98. doi: 10.2165/11534750-000000000-00000.
Results Reference
background
PubMed Identifier
21989078
Citation
Christensen MM, Brasch-Andersen C, Green H, Nielsen F, Damkier P, Beck-Nielsen H, Brosen K. The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c. Pharmacogenet Genomics. 2011 Dec;21(12):837-50. doi: 10.1097/FPC.0b013e32834c0010. Erratum In: Pharmacogenet Genomics. 2015 Jan;25(1):48-50.
Results Reference
background
PubMed Identifier
15966755
Citation
Timmins P, Donahue S, Meeker J, Marathe P. Steady-state pharmacokinetics of a novel extended-release metformin formulation. Clin Pharmacokinet. 2005;44(7):721-9. doi: 10.2165/00003088-200544070-00004.
Results Reference
background
PubMed Identifier
17476361
Citation
Shu Y, Sheardown SA, Brown C, Owen RP, Zhang S, Castro RA, Ianculescu AG, Yue L, Lo JC, Burchard EG, Brett CM, Giacomini KM. Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J Clin Invest. 2007 May;117(5):1422-31. doi: 10.1172/JCI30558.
Results Reference
background
PubMed Identifier
7306436
Citation
Tucker GT, Casey C, Phillips PJ, Connor H, Ward JD, Woods HF. Metformin kinetics in healthy subjects and in patients with diabetes mellitus. Br J Clin Pharmacol. 1981 Aug;12(2):235-46. doi: 10.1111/j.1365-2125.1981.tb01206.x.
Results Reference
background
PubMed Identifier
20587728
Citation
Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, Pollak M, Regensteiner JG, Yee D. Diabetes and cancer: a consensus report. Diabetes Care. 2010 Jul;33(7):1674-85. doi: 10.2337/dc10-0666.
Results Reference
background
PubMed Identifier
20299480
Citation
Bodmer M, Meier C, Krahenbuhl S, Jick SS, Meier CR. Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care. 2010 Jun;33(6):1304-8. doi: 10.2337/dc09-1791. Epub 2010 Mar 18.
Results Reference
background
PubMed Identifier
20947488
Citation
Decensi A, Puntoni M, Goodwin P, Cazzaniga M, Gennari A, Bonanni B, Gandini S. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res (Phila). 2010 Nov;3(11):1451-61. doi: 10.1158/1940-6207.CAPR-10-0157. Epub 2010 Oct 12.
Results Reference
background
PubMed Identifier
15849206
Citation
Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005 Jun 4;330(7503):1304-5. doi: 10.1136/bmj.38415.708634.F7. Epub 2005 Apr 22. No abstract available.
Results Reference
background
PubMed Identifier
19487376
Citation
Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, Hsu L, Hung MC, Hortobagyi GN, Gonzalez-Angulo AM. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol. 2009 Jul 10;27(20):3297-302. doi: 10.1200/JCO.2009.19.6410. Epub 2009 Jun 1.
Results Reference
background
PubMed Identifier
19375425
Citation
Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology. 2009 Aug;137(2):482-8. doi: 10.1053/j.gastro.2009.04.013. Epub 2009 Apr 16.
Results Reference
background
PubMed Identifier
19564453
Citation
Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care. 2009 Sep;32(9):1620-5. doi: 10.2337/dc08-2175. Epub 2009 Jun 29.
Results Reference
background
PubMed Identifier
19653109
Citation
Wright JL, Stanford JL. Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study. Cancer Causes Control. 2009 Nov;20(9):1617-22. doi: 10.1007/s10552-009-9407-y. Epub 2009 Aug 4.
Results Reference
background
PubMed Identifier
25053577
Citation
Xu H, Aldrich MC, Chen Q, Liu H, Peterson NB, Dai Q, Levy M, Shah A, Han X, Ruan X, Jiang M, Li Y, Julien JS, Warner J, Friedman C, Roden DM, Denny JC. Validating drug repurposing signals using electronic health records: a case study of metformin associated with reduced cancer mortality. J Am Med Inform Assoc. 2015 Jan;22(1):179-91. doi: 10.1136/amiajnl-2014-002649. Epub 2014 Jul 22.
Results Reference
background
PubMed Identifier
27004404
Citation
Chae YK, Arya A, Malecek MK, Shin DS, Carneiro B, Chandra S, Kaplan J, Kalyan A, Altman JK, Platanias L, Giles F. Repurposing metformin for cancer treatment: current clinical studies. Oncotarget. 2016 Jun 28;7(26):40767-40780. doi: 10.18632/oncotarget.8194.
Results Reference
background
PubMed Identifier
18006825
Citation
Dowling RJ, Zakikhani M, Fantus IG, Pollak M, Sonenberg N. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res. 2007 Nov 15;67(22):10804-12. doi: 10.1158/0008-5472.CAN-07-2310.
Results Reference
background
PubMed Identifier
24466367
Citation
Mohammed A, Janakiram NB, Brewer M, Ritchie RL, Marya A, Lightfoot S, Steele VE, Rao CV. Antidiabetic Drug Metformin Prevents Progression of Pancreatic Cancer by Targeting in Part Cancer Stem Cells and mTOR Signaling. Transl Oncol. 2013 Dec 1;6(6):649-59. doi: 10.1593/tlo.13556. eCollection 2013 Dec 1.
Results Reference
background
PubMed Identifier
20135346
Citation
Zakikhani M, Blouin MJ, Piura E, Pollak MN. Metformin and rapamycin have distinct effects on the AKT pathway and proliferation in breast cancer cells. Breast Cancer Res Treat. 2010 Aug;123(1):271-9. doi: 10.1007/s10549-010-0763-9. Epub 2010 Feb 5.
Results Reference
background
PubMed Identifier
20656475
Citation
Jalving M, Gietema JA, Lefrandt JD, de Jong S, Reyners AK, Gans RO, de Vries EG. Metformin: taking away the candy for cancer? Eur J Cancer. 2010 Sep;46(13):2369-80. doi: 10.1016/j.ejca.2010.06.012. Epub 2010 Jul 23.
Results Reference
background
PubMed Identifier
26720346
Citation
Poloz Y, Stambolic V. Obesity and cancer, a case for insulin signaling. Cell Death Dis. 2015 Dec 31;6(12):e2037. doi: 10.1038/cddis.2015.381.
Results Reference
background
PubMed Identifier
26111812
Citation
Camacho L, Dasgupta A, Jiralerspong S. Metformin in breast cancer - an evolving mystery. Breast Cancer Res. 2015 Jun 26;17(1):88. doi: 10.1186/s13058-015-0598-8.
Results Reference
background
PubMed Identifier
27076069
Citation
Dowling RJ, Lam S, Bassi C, Mouaaz S, Aman A, Kiyota T, Al-Awar R, Goodwin PJ, Stambolic V. Metformin Pharmacokinetics in Mouse Tumors: Implications for Human Therapy. Cell Metab. 2016 Apr 12;23(4):567-8. doi: 10.1016/j.cmet.2016.03.006. No abstract available.
Results Reference
background
PubMed Identifier
26330026
Citation
Kajbaf F, De Broe ME, Lalau JD. Therapeutic Concentrations of Metformin: A Systematic Review. Clin Pharmacokinet. 2016 Apr;55(4):439-59. doi: 10.1007/s40262-015-0323-x.
Results Reference
background
Citation
Glucophage XR product insert. https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0ahUKEwjcrMLO8cPXAhWGZiYKHVe1DoMQFggrMAA&url=https%3A%2F%2Fpackageinserts.bms.com%2Fpi%2Fpi_glucophage.pdf&usg=AOvVaw2zAbyMgwlF7wxaXv60vtv3.
Results Reference
background
PubMed Identifier
21617112
Citation
Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care. 2011 Jun;34(6):1431-7. doi: 10.2337/dc10-2361. No abstract available.
Results Reference
background
PubMed Identifier
19163997
Citation
Wadamori N, Shinohara R, Ishihara Y. Photoacoustic depth profiling of a skin model for non-invasive glucose measurement. Annu Int Conf IEEE Eng Med Biol Soc. 2008;2008:5644-7. doi: 10.1109/IEMBS.2008.4650494.
Results Reference
background
PubMed Identifier
22442396
Citation
Diabetes Prevention Program Research Group. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care. 2012 Apr;35(4):731-7. doi: 10.2337/dc11-1299.
Results Reference
background
PubMed Identifier
17638715
Citation
Bolen S, Feldman L, Vassy J, Wilson L, Yeh HC, Marinopoulos S, Wiley C, Selvin E, Wilson R, Bass EB, Brancati FL. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007 Sep 18;147(6):386-99. doi: 10.7326/0003-4819-147-6-200709180-00178. Epub 2007 Jul 16. Erratum In: Ann Intern Med. 2007 Dec 18;147(12):887.
Results Reference
background
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Metformin Pharmacology in Human Cancers: A Proof of Principle Study
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