Abstract:

Objective To explore the effects of metformin on the prognosis of type Ⅰ endometrial carcinoma (EC) patients complicated with type 2 diabetes mellitus (T2DM). Methods The clinical data of 45 type Ⅰ EC patients complicated with T2DM (T2DM group) and 147 type Ⅰ EC patients without diabetes mellitus (non-diabetes group) admitted to Qilu Hospital of Shandong University from January 2010 to December 2014 were retrospectively analyzed. The type Ⅰ EC patients with T2DM were divided into two groups, metformin group (n=23, taking metformin to control blood glucose in normal range) and non-metformin group (n=22, taking other hypoglycemic drugs or using insulin to control blood glucose in normal range). The clinicopathological characteristics of T2DM group and non-diabetes group were compared, and the effects of metformin on the prognosis of type Ⅰ EC patients with T2DM were analyzed. Results Compared with non-diabetes group, the type Ⅰ EC patients in T2DM group have the older onset age (t=4.331, P<0.001), more complicated with hypertension (χ²=19.252, P<0.001), later surgical pathological stage (χ²=4.588, P=0.032), higher histological grade (χ²=6.069, P=0.048), deeper myometrial infiltration (χ²=7.743, P=0.005) and higher incidence of lymph node metastasis (χ²=4.885, P=0.027). The median progression-free survival (PFS) (47.0 months vs. 38.0 months) and median overall survival (OS) (52.0 months vs. 41.0 months) in metformin group were significantly longer than those in non-metformin group (χ²=10.899, P=0.001; χ²=10.090, P=0.001). There was no significant difference in median PFS (47.0 months vs. 46.0 months) and median OS (52.0 months vs. 46.0 months) between metformin group and non-diabetes group (χ²=0.791, P=0.374; χ²=0.836, P=0.360). Cox multivariate analysis showed that the risk factors of PFS and OS in type ⅠEC patients were old onset age(OR=2.128, 95%CI: 1.361-3.328, P=0.001; OR=4.502, 95%CI: 1.696-11.954, P=0.003), late surgical pathological stage(OR=2.231, 95%CI: 1.437-3.462, P=0.001; OR=4.005, 95%CI: 1.480-10.836, P=0.006), high histological grade(P=0.001; P=0.017; G2 vs.G1: OR=5.660, 95%CI: 3.424-9.357, P=0.001; OR=5.763, 95%CI: 1.666-19.938, P=0.006), deep myometrial invasion(OR=1.531, 95%CI: 1.049-2.235, P=0.027; OR=3.759, 95%CI: 1.890-7.476, P=0.001), positive lymph node metastasis (OR=11.277, 95%CI: 2.774-45.838, P=0.001; OR=8.451, 95%CI: 1.138-62.767, P=0.037)and T2DM (OR=1.897, 95%CI: 1.096-3.281, P=0.008; OR=1.813, 95%CI: 1.043-3.151, P=0.012). Metformin was the protective factor of PFS (OR=0.412, 95%CI: 0.207-0.818, P=0.002) and OS (OR=0.455, 95%CI: 0.228-0.905, P=0.008) in type Ⅰ EC patients with T2DM. Conclusion Complication with T2DM is the negative factor on the prognosis of type Ⅰ EC patients. Intake of metformin can significantly improve the PFS and OS of type Ⅰ EC patients complicated with T2DM and improve the prognosis.

Key words: Diabetes mellitus, type 2, Endometrial neoplasms, Metformin, Prognosis