Vol 10, No 3 (2021)
Research paper
Published online: 2020-11-23

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The anti-proliferative role of metformin in non-diabetic female patients with breast cancer: systematic review and meta-analysis of randomized control trials

Hanan A Al-Ghalib12, Afnan D Al-Otaibi12, Bader Al Tulaihi3, Shatha Al-Ghaleb4
Clin Diabetol 2021;10(3):252-260.


Background. Usage of metformin in non-diabetic women
with breast cancer is neither a common approach
nor a conventional treatment modality. Metformin
and chemotherapy have a high phenotypic variation
in complete response rate among diabetic patients
with different types of cancer. Although the results
on salvage therapy were contradictory, we carried out
a meta-analysis to evaluate the effect of the addition
of metformin to conventional treatment on the prognosis
in non-diabetic women who have breast cancer.

Methods. A consummate literature search of Pub-
Med, EMBASE, grey literature, and web of science
was conducted until 7th of March 2020. A total of 11
randomized control trials were included in this metaanalysis
including references related to metformin,
breast cancer, and prognosis. The search was limited to
English language and human studies, including references
related to metformin, breast cancer, and prognosis.
We performed the meta-analysis using a random
and fixed-effects model, with hazard ratios and 95%
confidence intervals (95% CI) as effect measures.

Results. A total of 11 randomized control trials consisting
of 1681 breast cancer patients without diabetes
including 841 ones which received metformintreatement
versus 840 ones not treated with metformin.
The meta-analysis found that metformin has been
linked with anti-proliferative role (HR 0.63, 95% CI
0.59–0.71). Subgroup analysis showed an increased average
progression of free survival which demonstrates
that metformin improves overall survival by 65% after
correcting for hormone-receptor/gene expression (HR
0.35, 95% CI 0.15–0.84). Taking metformin as treatment
of breast cancer has been related to extended
survival rate.

Conclusion. This meta-analysis supports the potential
role of metformin in the management of cancer, as it
may increase progression free survival among nondiabetic
patients with breast cancer. More clinical trials
are needed for further exploration of metformin role,
and to determine whether improvements in cancer
care can be achieved with adding metformin to reduce
mortality or to improve overall survival in patients with
breast cancer.

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