Continuous use of metformin can improve survival in type 2 diabetic patients with ovarian cancer

Abstract

Evidence indicates that type 2 diabetes may stimulate the initiation and progression of several types of cancer. Metformin, a drug most commonly used to treat type 2 diabetes, may inhibit cancer cell growth and reduce the risk of cancer. However, evidence of the antitumor effects of metformin on ovarian cancer is still limited.In this study, we retrospectively examined the effects of metformin on ovarian cancer patients with diabetes at our institution.We identified 568 consecutive patients who were newly diagnosed with ovarian cancer and treated between January 2011 and March 2014. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to IV epithelial ovarian, fallopian, or peritoneal cancer were included. Patients with type 1 diabetes, incomplete records (including medication records) and any other cancer before their ovarian cancer diagnosis, as well as those diagnosed with diabetes more than 6 months after their ovarian cancer diagnosis, were excluded. Out of 568 patients, 48 (8.5%) patients with type 2 diabetes continuously used metformin, 34 (5.9%) patients with type 2 diabetes did not take metformin, 22 (3.9%) patients with type 2 diabetes discontinued metformin, and 464 (81.7%) ovarian cancer patients were nondiabetic controls. Longer progression-free survival (PFS) and overall survival (OS) were observed in ovarian cancer patients with diabetes who were taking metformin than in diabetic patients not taking metformin, diabetic patients who discontinued metformin, and nondiabetic ovarian cancer patients (P = .001). After adjusting for possible confounders, metformin use was associated with a lower risk for disease relapse [hazard ratio (HR) = 0.34; 95% confidence interval (CI): 0.27–0.67; P < .01] and disease-related death (HR = 0.29; 95% CI: 0.13–0.58, P = .03) among ovarian cancer patients with diabetes.Metformin use may decrease the risk for disease recurrence and death in patients with ovarian cancer, but the drug treatment must be continuous.

Prognosis of ovarian cancer in women with type 2 diabetes using metformin and other forms of antidiabetic medication or statins: a retrospective cohort study

“…The results of some previous studies have suggested that metformin use is associated with better survival in cases of ovarian cancer [ 6 – 8 , 37 ] unlike in our study, whereas similarly to our findings, in one study such an association was not found [ 38 ]. The most recent study on metformin and OC survival also suggested that continuous use of metformin in women with T2D decreases the occurrence of relapses of ovarian cancer and ovarian cancer-related deaths [ 37 ]. In line with our findings, Garcia et al found no association between metformin use and better overall survival [ 38 ].…”

<p>Correlation of NRF2 and progesterone receptor and its effects on ovarian cancer biology</p>

“…incidence and survival, it was proposed that metformin should be followed as an additional approach in ovarian cancer treatment. [63][64][65] As metformin treatment is associated with an increased PR expression, these results further support future investigations of the above-described relationships in the NRF2/AKR1C1/PR pathway and their impact on ovarian cancer biology and the clinical behavior.…”

Synergistic therapeutic effects of metformin at a clinically relevant dosage in combination with chemotherapy via the AKT/mTOR pathway on ovarian cancer

“…Many studies have shown that metformin can reduce the risk of cancer, including breast, colon, liver, and pancreatic cancers, and improve outcomes over those obtained with other antidiabetic treatments (sulfonylurea, insulin) in diabetic patients [9]. Whether metformin can reduce the risk of ovarian cancer has been investigated [22][23][24], but few studies have focused on the effects of metformin combined with commonly used rst-line chemotherapeutic drugs, such as carboplatin, and the underlying mechanisms [25]. Neoadjuvant metformin combined with other therapies have been administered to treat ER-positive breast cancer in a Phase II clinical trial (ClinicalTrials.gov Identi er: NCT01589367).…”