Expanding the therapeutic spectrum of metformin: from diabetes to cancer

Abstract

If in vitro data appear solid, the results provided by in vivo studies are somehow controversial. In this view, larger studies are needed to fully elucidate the role of metformin on cancer development and progression, as well as the specific clinical settings in which metformin could become an anti-cancer drug.

Antidiabetic medications use and cancer risk in type 2 diabetes

“…Cancer-free survival among patients using different treatment models. Differences between all groups were insignificant, p > 0.05 production and improving insulin sensitivity [4,16,17]. Moreover, it is possible that metformin may also play an additional immunomodulatory role [18].…”

“…However, some authors did not found any protective effect of metformin on cancer development [12] or contests those associations due to the limitations of observational studies [13]. Nevertheless, a vast majority of evidence indicate reduced cancer risk among metformin users, which was confirmed in two large meta-analyses [4,14]. The anti-cancer action of metformin includes both direct and indirect effect on cancer cells growth.…”

“…A direct effect is mediated by mechanisms dependent and also independent of AMPK (AMP-activated protein kinase) pathways. Stimulation of AMPK and its regulator LKB1 (liver kinase B1), by inhibiting mTOR (mammalian target of rapamycin) pathway acts as a tumor suppressor protein [4,15]. But metformin can also inhibit cancer growth through several AMPK-independent pathways, including, amongst others, direct inhibition of mTOR and influence the energy state of the cell [4].…”

“…Stimulation of AMPK and its regulator LKB1 (liver kinase B1), by inhibiting mTOR (mammalian target of rapamycin) pathway acts as a tumor suppressor protein [4,15]. But metformin can also inhibit cancer growth through several AMPK-independent pathways, including, amongst others, direct inhibition of mTOR and influence the energy state of the cell [4]. Indirect effect of metformin on cancer growth includes also its insulin-lowering action by reducing hepatic glucose Figure 3.…”

“…Also glucose-lowering agents may influence the risk of malignancy in diabetic patients. The vast majority of evidence has indicated protective role of metformin and provided ambiguous data on other antidiabetic agents, most notably insulin, but also incretin-based therapies [1][2][3][4][5]. However, it should be remembered that T2DM is a progressive disease and treatment intensification over time is usually required.…”