Thanida Tangjarusritaratorn,1 Watip Tangjittipokin,1,2 Then Kunavisarut3
1Department of Immunology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 2Siriraj Research Excellence Center for Diabetes and Obesity, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 3Department of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
Correspondence: Tada Kunavisarut
Department of Endocrinology and Metabolism, Medical Department, Medical School, Siriraj Hospital, Mahidol University, Road 2 Prannok, Bangkoknoi, Bangkok, 10700, Thailand
Tel +66 2-419-7799
Fax +66 2-419-7792
Email [email protected]
Purpose: To evaluate the benefit of metformin on the incidence and survival of hepatocellular carcinoma (HCC) in cirrhosis in patients with type 2 diabetes mellitus (T2DM).
Patients and methods: We conducted a retrospective study from 2006 to 2019. Patients were assigned metformin exposure if they were given metformin for at least 3 months after the diagnosis of cirrhosis. Outcomes were the incidence and survival of HCC in T2DM with metformin-treated cirrhosis compared with those not treated with metformin. For the incidence of HCC, the follow-up time was 5 years after the diagnosis of cirrhosis. For the survival of HCC, we censored vital status in June 2019.
Results: Of the 1061 patients, patients were divided into 719 patients with metformin exposure and 342 with non-metformin exposure. In metformin exposure, 125 patients (17.4%) developed HCC. In non-metformin exposure, 128 patients (37.4%) developed HCC. Metformin exposure had a significantly lower risk of developing HCC in a multivariate HR analysis of 0.48 (0.36–0.61); P <0.001. To survive HCC, 327 patients were recruited. One hundred and sixty-two patients were exposed to metformin, and 165 patients were exposed to metformin. Sixty patients (37%) in metformin exposure died, while 84 patients (50.9%) in unexposed metformin died. The median survival of metformin exposure and non-metformin exposure was 6.9 years and 3.88 years, respectively; P = 0.003. In the univariate analysis, metformin exposure was significantly associated with better survival than in the non-exposure group, HR 0.63 (0.45–0.88); P = 0.006. No significant difference was observed in the multivariate analysis between the two groups, HR 1.07 (0.74–1.54); P = 0.72.
Conclusion: Metformin exposure was associated with a lower incidence of HCC in cirrhosis in patients with T2DM and appeared to prolong survival. Continued use of metformin in patients with cirrhosis with T2DM should be considered if there are no contraindications.
Keywords: type 2 diabetes mellitus, cirrhosis, hepatocellular carcinoma, metformin
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