Metformin: not only per os

Figures & data

Table 1. Potential routes of metformin administration (Already studied or proposed).

Route	Present state of implication
Oral use	Routine clinical practice
Injections into lateral brain ventricles	Experimental study in animals [6]
Topical use in skin lesions	Experimental studies in animals [7–9]
Injections in periodontal pockets at chronical periodontitis	Clinical approbation in patients [10]
Rectal biguanide infusions in an inflammatory bowel disease	Mouse model [12]
Rectal suppositories	Bioavailability of metformin-containing formulation is evaluated in human volunteers [14]
Subcutaneous injections	Peritumoral injections of hydrogel containing metformin and 5-fluorouracil were tested in BALB/c mice inoculated with colon adenocarcinoma C26 cells [15]
Intravenous injections	Liposomal combination of metformin and anthracycline (epirubicin) is described in transplanted S180 mouse sarcoma model [16]
Intratumoral injections	Xenografts of prostate cancer and melanoma cells grown in female mice[18]
Intravesical administration of metformin solution	Preclinical murine model of bladder cancer [19]
Suggested but not yet studied approaches
Inhalation [17]
Eye drops^This paper
Intrauterine administration^This paper

Sublingual rout, at least as we are aware, was not so far mentioned

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Zaghloul AA, Lila A, Abd-Allah F, et al. Preparation and in vitro/in vivo evaluation of metformin hydrochloride rectal dosage forms for treatment of patients with type II diabetes. J Drug Target. 2017;25(5):463–470.

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Wu X, He C, Wu Y, et al. Synergistic therapeutic effects of Schiff’s base cross-linked injectable hydrogels for local co-delivery of metformin and 5-fluorouracil in a mouse colon carcinoma model. Biomaterials. 2016;75:148–162.

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Yang Q, Zhang T, Wang C, et al. Coencapsulation of epirubicin and metformin in PEGylated liposomes inhibits the recurrence of murine sarcoma S180 existing CD133+ cancer stem-like cells. Eur J Pharm Biopharm. 2014;88(3):737–745.

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Hirsch HA, Iliopoulos D, Struhl K. Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth. Proc Natl Acad Sci USA. 2013;110(3):972–977.

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Peng M, Su Q, Zeng Q, et al. High efficacy of intravesical treatment of metformin on bladder cancer in preclinical model. Oncotarget. 2016;7(8):9102–9117.

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Menendez JA, Quirantes-Piné R, Rodríguez-Gallego E, et al. Oncobiguanides: paracelsus’ law and nonconventional routes for administering diabetobiguanides for cancer treatment. Oncotarget. 2014;5(9):2344–2348.

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