Metformin Use and Survival in Patients with Advanced Extrahepatic Cholangiocarcinoma: A Single-Center Cohort Study in Fuyang, China

Abstract

Aims. Metformin is an oral antidiabetic agent that has been widely prescribed for the treatment of type II diabetes. In recent years, anticancer properties of metformin have been revealed for numerous human malignancies. However, there are few indications available regarding the feasibility and safety of these studies in an advanced extrahepatic cholangiocarcinoma (EHCC) population. This study is aimed at evaluating the feasibility, safety, and value of metformin use and survival in patients with advanced EHCC. Methods. All patients with advanced EHCC observed at Fuyang People’s Hospital between January 2015 and November 2020 were included in the study. Case data, clinical information, and imaging results were abstracted from the self-administered questionnaire and electronic medical record. All patients were divided into study subjects and control subjects, and the study subjects were given metformin, 0.5 g, three times a day, while control subjects were without metformin. The metformin use and survival time of the subjects were asked by telephone, out-patient, or door-to-door visit, after they left the hospital. Results. One hundred and thirty-three study cases and 589 controls were included in the analysis. This study showed that metformin use cannot improve the overall survival rate of patients with advanced EHCC ([95% CI]: -17.05-0.375, t = − 1.889 , P value = 0.061), but the survival time of patients with drainage treatment from control group ( n = 496 ) was significantly shorter than that of patients with drainage treatment from the study group ( n = 113 ), and the difference was statistically significant ( z = − 2.230 , P value = 0.026). There were significant differences between metformin used before or after the diagnosis of advanced EHCC (OR[95% CI], 3.432[2.617-4.502]; P value = 0.001) in survival time. And there was significant difference between the duration of metformin use and survival prognosis (OR[95% CI], 2.967[1.383-6.368]; P = 0.005 ). Conclusion. Metformin can improve the survival of advanced EHCC patients who underwent drainage treatment, especially for metformin use after diagnosis of advanced EHCC and long duration of metformin.

Effects of Metformin on Risk and Prognosis of Biliary Tract Cancer: A Systematic Review and Meta-Analysis

“…The pooled results showed no significant correlation between metformin use and OS (HR = 0.88, 95% CI: 0.74–1.04, p overall effect = 0.135) [ 21 , 24 , 30 , 35 ] ( Figure 2 B). The other remaining study found similar results (95% CI: −17.05–0.375; p overall effect = 0.061) [ 29 ].…”

“…The remaining 34 studies were read in full, among which 13 studies did not investigate the efficacy of metformin on BTC, 4 studies did not explore risks or prognostic endpoints for BTC, 3 studies were cellular or animal studies, and 3 studies were duplicate reports of the same study. Finally, a total of 11 studies were included in the meta-analysis [ 21 , 22 , 23 , 24 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. The detailed process of study selection is presented in Figure 1 .…”

“…A total of 11 studies involving 24,788,738 participants were finally included: two studies from each of the following countries: Italy, China, and the USA; and one study from each of the following countries: Thailand, Korea, Netherlands, Canada, and Sweden. Seven studies explored the effect of metformin on the risk of BTC [ 21 , 22 , 23 , 31 , 32 , 33 , 34 ], five explored its effect on OS [ 21 , 24 , 29 , 30 , 35 ], and two explored its effect on DFS [ 30 , 35 ]. The studies that reported median/mean age all ranged from 60 to 70.…”

“…Five studies comprising 306,697 participants assessed the effects of metformin on OS in patients with BTC [ 21 , 24 , 29 , 30 , 35 ]. Among them, four studies provided eligible data types for inclusion in the meta-analysis; the level of heterogeneity between studies was subtle ( I 2 = 0.0%, p heterogeneity = 0.657), and therefore a fixed-effects model was used.…”

PGC-1α activity and mitochondrial dysfunction in preterm infants

“…Metformin attenuates inflammation and prevents the onset of ARDS by decreasing IL-1β and IL-6 mRNA and protein production, and NLRP3 inflammasome activation in mice ( Xian et al, 2021 ). Additionally, it alleviates pulmonary fibrosis and prevents PH in pre-clinical studies ( Agard et al, 2009 ; Chan and Rubin, 2017 ; Goncharov et al, 2018 ; Liu et al, 2019a ; Mulkareddy and Simon, 2020 ; Cheng et al, 2021 ; Wu et al, 2021 ).…”