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Review
. 2024 Mar 26;16(7):1287.
doi: 10.3390/cancers16071287.

Ianus Bifrons: The Two Faces of Metformin

Umberto Goglia  1 , Iderina Hasballa  2   3 , Claudia Teti  4 , Mara Boschetti  2   3 , Diego Ferone  2   3 , Manuela Albertelli  2   3
Affiliations
Review

Ianus Bifrons: The Two Faces of Metformin

Umberto Goglia et al. Cancers (Basel). .

Abstract

The ancient Roman god Ianus was a mysterious divinity with two opposite faces, one looking at the past and the other looking to the future. Likewise, metformin is an "old" drug, with one side looking at the metabolic role and the other looking at the anti-proliferative mechanism; therefore, it represents a typical and ideal bridge between diabetes and cancer. Metformin (1,1-dimethylbiguanidine hydrochloride) is a drug that has long been in use for the treatment of type 2 diabetes mellitus, but recently evidence is growing about its potential use in other metabolic conditions and in proliferative-associated diseases. The aim of this paper is to retrace, from a historical perspective, the knowledge of this molecule, shedding light on the subcellular mechanisms of action involved in metabolism as well as cellular and tissue growth. The intra-tumoral pharmacodynamic effects of metformin and its possible role in the management of different neoplasms are evaluated and debated. The etymology of the name Ianus is probably from the Latin term ianua, which means door. How many new doors will this old drug be able to open?

Keywords: biguanide; cancer treatment; clinical trials; diabetes; glucose control; metformin.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Ianus Bifrons sculpture (https://iStock.com/ accessed on 22 May 2023).
Figure 2
Figure 2
(A,B) Frontspiece of Volume XXI of John Hill’s huge work and graphic reproduction of Galena officinalis, p54, 1772 [2]. (C) Photo of Galena officinalis by Peter Smith, Aylestone Meadows, 10 July 2013, www.natarespot.org.uk (accessed on 22 May 2023).
Figure 3
Figure 3
Absorption, uptake, and elimination of metformin. After oral intake, absorption in the gastrointestinal tract is mediated by specific molecular transporters that allow a drug concentration in the portal system of 40–70 µmol/L, higher than that in systemic circulation (10–40 µmol/L). Metformin is excreted unchanged in the urine, and active tubular secretion in the kidney is the main route of drug elimination. PMAT: plasma membrane monoamine transporter (expressed within the apical membranes of enterocytes in the small intestine, and variants are associated with poor tolerance in subjects affected by diabetes mellitus). OCT1/2/3: organic cation transporter. MATE1/2: multidrug and toxin extrusion proteins.
Figure 4
Figure 4
Direct (left) and indirect (right) pathways involved in the molecular mechanisms of the antineoplastic role of metformin. For specific actions of subcellular signals, see the text.
See this image and copyright information in PMC

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