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. 2016 Jan 20;11(1):e0147145.
doi: 10.1371/journal.pone.0147145. eCollection 2016.

Association of Metformin Use with Outcomes in Advanced Endometrial Cancer Treated with Chemotherapy

Obiageli Ezewuiro  1 , Tatyana A Grushko  1 , Masha Kocherginsky  2 , Mohammed Habis  3 , Jean A Hurteau  4 , Kathryn A Mills  3 , Jessica Hunn  3 , Olufunmilayo I Olopade  1 , Gini F Fleming  1 , Iris L Romero  3
Affiliations

Association of Metformin Use with Outcomes in Advanced Endometrial Cancer Treated with Chemotherapy

Obiageli Ezewuiro et al. PLoS One. .

Abstract

There is increasing evidence that metformin, a commonly used treatment for diabetes, might have the potential to be repurposed as an economical and safe cancer therapeutic. The aim of this study was to determine whether stage III-IV or recurrent endometrial cancer patients who are using metformin during treatment with chemotherapy have improved survival. To test this we analyzed a retrospective cohort of subjects at two independent institutions who received chemotherapy for stage III-IV or recurrent endometrial cancer from 1992 to 2011. Diagnosis of diabetes, metformin use, demographics, endometrial cancer clinico-pathologic parameters, and survival duration were abstracted. The primary outcome was overall survival. The final cohort included 349 patients, 31 (8.9%) had diabetes and used metformin, 28 (8.0%) had diabetes but did not use metformin, and 291 (83.4%) did not have diabetes. The results demonstrate that the median overall survival was 45.6 months for patients with diabetes who used metformin compared to 12.5 months for patients with diabetes who did not use metformin and 28.5 months for patients without diabetes (log-rank test comparing the three groups P = 0.006). In a model adjusted for confounders, the difference in survival between the three groups remained statistically significant (P = 0.023). The improvement in survival among metformin users was not explained by better baseline health status or more aggressive use of chemotherapy. Overall, the findings in this retrospective cohort of endometrial cancer patients with stage III-IV or recurrent disease treated with chemotherapy indicate that patients with diabetes who were concurrently treated with metformin survived longer than patients with diabetes who did not use metformin.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Study selection criteria and primary exposures.
Fig 2
Fig 2. Kaplan-Meier estimates of overall survival.
The three groups are: endometrial cancer patients with type II diabetes taking metformin; endometrial cancer patients without diabetes; and endometrial cancer patients with diabetes not taking metformin. P values are from the Cox model adjusting for study site.
Fig 3
Fig 3. Kaplan-Meier estimates of overall survival.
The three groups are: endometrial cancer patients with type II diabetes taking metformin; endometrial cancer patients without diabetes; and endometrial cancer patients with diabetes not taking metformin. P values are from the Cox model adjusting for study site. (a) Patients with stage III disease. (b) Patients with stage IV or recurrent disease.
See this image and copyright information in PMC

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