The benefits of adding metformin to tamoxifen to protect the endometrium—A randomized placebo‐controlled trial

Davis, Susan R.; Robinson, Penelope Jane; Jane, Fiona; White, Shane; Brown, Kristy A.; Piessens, Sofie; Edwards, Andrew M.; McNeilage, Jane; Woinarski, Jillian; Chipman, M; Bell, Robin J.

doi:10.1111/cen.13830

Cited by 23 publications

(25 citation statements)

References 38 publications

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“…Our data indicated that the metformin in a dose of 1700 mg per day had an a signi icant inhibitory role concerning tamoxifen induced uterine cell proliferation as the results showed that the uterine thickness of a control group (B) who do not use metformin, was signi icantly increased or higher in comparison to diabetic patients on metformin therapy. These indings in line with Davis et al (2018) who were studied 112 women with breast cancer on tamoxifen therapy and found the median endometrium thickness after 52 weeks of therapy with metformin was signi icantly lower for the metformin (n = 36) group than for the placebo group (n = 45) (2.3 mm (ranged from 1.4 to 7.8) vs 3.0 (ranged from 1.2 to 11.3), as well as they, found that 13.3% who were assigned to placebo had an endometrium thickness greater than 4 mm vs 5.7% for metformin. (Erdemoglu et al, 2009), (Zhao et al, 2018) and (Hanawa et al, 2018), reported substantial evidence that metformin may protect the endometrium against risk factors by local inhibition of mTOR (Target of rapamycin) which is a highly conserved serine/threonine kinase that controls cell growth and metabolism in response to nutrients, growth factors, cellular energy, and stress either through activation of the human tumor suppressor LKB1/AMPK pathway and indirectly via targets associated with insulin resistance.…”

Section: Resultssupporting

confidence: 82%

Inhibitory role of Metformin for tamoxifen induced ‎uterine cell proliferation in diabetic ‎patients with ER-‎positive Breast cancer

Abd-Alhussain

Alatrakji

Saleh

et al. 2019

ijrps

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The objective of the current work to evaluate the role of metformin in inhibiting the tamoxifen induced ‎endometrial ‎changes in diabetic patients with ER-positive breast cancer, a case-control study, carried out between December 2018 to May 2019, forty ‎diabetic women in postmenopausal phase with ER+ breast cancer on tamoxifen (20mg/day), ‎metformin ‎‎(1700 mg/day) GROUP A, and 40 diabetic patients with ER+ breast cancer on the ‎same dose of tamoxifen, but other hypoglycemic agent GROUP B, were selected as controls. ‎Uterine thickness was assessed by ultrasonography imaging at the beginning of treatment with ‎tamoxifen and after 2 years of treatment. Hysteroscopy ‎was done, and pathological findings also ‎recorded.‎ Mean uterine thickness of diabetic patients on other hypoglycemic was ‎significantly higher than diabetic patients on metformin (14.79±3.6 vs 4.37±1.8). Uterine ‎thickness >5mm were 2 (5%) vs ‎36 (85%) reported with the diabetic patient on metformin and the ‎diabetic patient on ‎other oral hypoglycemic group. Three cases (7.5%) of the diabetic patients ‎on other hypoglycemic agent were developed uterine polyps, and one case (2.5%) of diabetic ‎patients on metformin were developed uterine polyps. One case (2.5%) of uterine carcinoma ‎was reported with diabetic patients on other hypoglycemic group.‎ In conclusions metformin significantly inhibit tamoxifen-induced endometrial changes and ‎offers favorable endometrium protection.

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Section: Resultssupporting

confidence: 82%

Inhibitory role of Metformin for tamoxifen induced ‎uterine cell proliferation in diabetic ‎patients with ER-‎positive Breast cancer

Abd-Alhussain

Alatrakji

Saleh

et al. 2019

ijrps

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“…Contrary to this finding, a recent phase III study did not find reduced tumour proliferation in endometrial cancer among metformin users (21). Metformin has also been found to prevent tamoxifenassociated endometrial proliferative changes in breast cancer patients (22).…”

Section: Discussionmentioning

confidence: 78%

Metformin Associates With Aggressive Features of Endometrial Cancer in Women With Type 2 Diabetes

et al. 2021

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“…Those untreated with metformin showed worse disease-free and overall survival than patients receiving metformin. Another trial studied the effect of metformin on endometrial changes and insulin resistance induced by tamoxifen in breast cancer [50]. Postme nopausal women with hormone receptor-positive breast cancer were randomized to receive 850 mg of metformin 2× daily or placebo for 52 weeks.…”

Section: Discussionmentioning

confidence: 99%

Metformin in Oncology – How Far Is Its Repurposing as an Anticancer Drug?

Pácal¹,

Kaňková²

2020

Klin Onkol

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Background:Metformin is the most commonly used antidiabetic drug with a plethora of proven metabolic and cardiovascular beneficial effects and exceptional safety profile. On top of the established metabolic effects, retrospective epidemiologic evidence shows that metformin use is associated with decreased cancer risk and/ or improved disease prognosis in diabetic cancer patients on metformin compared to those treated with different antidiabetic drugs. This is a sound argument for eventual repurposing metformin as an adjuvant drug in oncology; however, evidence-based data are currently needed to establish this. Metformin is a biguanide that in the context of type 2 diabetes primarily targets the liver. Metformin inhibits oxidative phosphorylation which leads to the suppression of gluconeogenesis and causes decrease of blood glucose concentration. Mechanisms responsible for metformin anti-neoplastic effect have been investigated extensively, and key events seem to centralize around its ability to induce intracellular energetic stress with subsequent changes of metabolism resulting in cytostatic or cytotoxic action. Large clinical experience with metformin in the treatment of diabetes together with its plausible effects on different cancer cell types initiated a number of clinical trials that tested the hypothesis that metformin might have a beneficial effect in the treatment of cancer. Purpose: The aim of this review is to compile recent advances in our understanding of metformin antineoplastic effects and to give a summary of the results of recent clinical trials of metformin for treatment of different cancer types. SouhrnVýchodiska: Metformin je lékem první volby u diabetiků, lékem stále šířeji využívaným i v nediabetické populaci, a to zejména díky kombinaci efektivity a excelentního bezpečnostního profilu. Nad rámec známých metabolických efektů prokázaly retrospektivní epidemiologické studie, že užívání metforminu u diabetiků snižuje riziko vzniku nádorů a/ nebo zlepšuje prognózu ve srovnání s těmi, kteří užívají jiná antidiabetika. Toto je velmi silný argument pro to, uvažovat o změně účelu indikace metforminu jako případného adjuvancia v onkologických indikacích, nicméně je bezpodmínečně nutné ověřit tuto domněnku v duchu medicíny založené na důkazech. Metformin patří mezi biguanidy a v kontextu diabetu typu 2 zvyšuje citlivost tkání k inzulinu. Účinkuje především na úrovni jater, kde inhibuje oxidativní fosforylaci, což vede k supresi glukoneogeneze a způsobuje pokles koncentrace glukózy v krvi. Působí také na svalové a tukové buňky, ve kterých zlepšuje utilizaci glukózy. Mechanizmy zodpovědné za protinádorový účinek metforminu jsou detailně studovány a zdá se, že nejdůležitější je jeho schopnost vyvolat intracelulární energetický stres a následně metabolické změny, které mají cytostatický nebo cytotoxický efekt. Rozsáhlá klinická zkušenost s metforminem v léčbě diabetu v kombinaci s jeho prokázaným efektem na různé typy nádorových buněk vedla k zahájení mnoha klinických studií, které testovaly jeho potenciá...

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The benefits of adding metformin to tamoxifen to protect the endometrium—A randomized placebo‐controlled trial

Abstract: Metformin appears to inhibit tamoxifen-induced endometrial changes and has favourable metabolic effects. Further research into the adjuvant use of metformin after breast cancer and to prevent EH and cancer is warranted.

Cited by 23 publications

References 38 publications

Inhibitory role of Metformin for tamoxifen induced ‎uterine cell proliferation in diabetic ‎patients with ER-‎positive Breast cancer

Inhibitory role of Metformin for tamoxifen induced ‎uterine cell proliferation in diabetic ‎patients with ER-‎positive Breast cancer

Metformin Associates With Aggressive Features of Endometrial Cancer in Women With Type 2 Diabetes

Metformin in Oncology – How Far Is Its Repurposing as an Anticancer Drug?

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