The Association of Metformin, Other Antidiabetic Medications, and Statins with the Prognosis of Hepatocellular Carcinoma in Patients with Type 2 Diabetes: A Retrospective Cohort Study

Author:

Tuunanen Iida123,Hautakoski Ari23,Huhtamäki Heikki4,Arffman Martti5ORCID,Sund Reijo6ORCID,Puistola Ulla123ORCID,Karihtala Peeter7ORCID,Jukkola Arja8,Urpilainen Elina123ORCID

Affiliation:

1. Department of Obstetrics and Gynecology, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, University of Oulu, 90220 Oulu, Finland

2. Research Unit of Clinical Medicine, University of Oulu, 90220 Oulu, Finland

3. Medical Research Center, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, University of Oulu, 90220 Oulu, Finland

4. Research Unit of Mathematical Sciences, Faculty of Science, University of Oulu, 90014 Oulu, Finland

5. Department of Public Health and Welfare, Finnish Institute for Health and Welfare, 00271 Helsinki, Finland

6. Institute of Clinical Medicine, University of Eastern Finland, 70029 Kuopio, Finland

7. Department of Oncology, University of Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00029 Helsinki, Finland

8. Department of Oncology and Radiotherapy, Tays Cancer Center, Tampere University Hospital, Faculty of Medicine and Health Technology, Tampere University, 33521 Tampere, Finland

Abstract

This study aimed to explore whether the prediagnostic use of metformin and statins is associated with the prognosis of patients with hepatocellular carcinoma (HCC) and type 2 diabetes. We identified 1383 eligible individuals who had both type 2 diabetes and HCC diagnosed between 1998 and 2017 from several Finnish registers. Cox models were fitted for cause-specific and all-cause mortality in relation to the use of antidiabetic medications and statins prior to the HCC diagnosis. Prediagnostic metformin use was associated with decreased overall mortality (hazard ratio 0.84, 95% confidence interval 0.74–0.94) compared with nonuse in patients with type 2 diabetes. Similarly, slightly decreased HCC mortality and other-cause mortality were observed among metformin users. The results were inconclusive regarding metformin use and both overall and HCC mortality among patients with localized HCC. No discernible contrast between statin users and nonusers was found in overall mortality nor HCC mortality in either the whole cohort or patients with localized cancer.

Funder

Jane and Aatos Erkko Foundation

Jenni Piirainen Foundation

Publisher

MDPI AG

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