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Int J Cancer. 2019 Jan 15;144(2):273-280. doi: 10.1002/ijc.31783. Epub 2018 Oct 26.

Use of metformin and survival of patients with high-grade glioma.

Author information

1
Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany.
2
Institute for Quality Assurance and Health Services Research, University of Regensburg, Regensburg, Germany.
3
Department of Neurosurgery, Regensburg University Hospital, Regensburg, Germany.
4
Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany.
5
Basel Pharmacoepidemiology Unit, Division of CIinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Switzerland.
6
Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, USA.
7
Department of Pharmaceutical Sciences, Hospital Pharmacy, University Hospital Basel, Switzerland.
8
Department of Epidemiology and Preventive Medicine, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.

Abstract

High-grade glioma (HGG) is associated with poor prognosis. Drug repurposing evolves as new modality to improve standard therapy. The antidiabetic drug metformin has been found to inhibit glioma cell growth in vitro and in vivo. The aim of the present retrospective cohort study was to evaluate the survival of patients with HGG with or without treatment with metformin, based on a large cohort of a cancer registry. The analysis included 1,093 patients with HGG diagnosed between 1998 and 2013 from the population-based clinical cancer registry Regensburg (Germany), which covers 2.1 Mio inhabitants and 98% of all cancer diagnoses. We performed multivariable adjusted Cox-regression analyses. Hazard Ratios (HRs) with 95% Confidence Intervals (CIs) for overall survival (OS) and progression-free survival (PFS) of patients with HGG with or without treatment with metformin were obtained. Use of metformin was associated with a significantly better overall and progression-free survival of patients with WHO grade III glioma (HR for OS = 0.30; 95% CI = 0.11-0.81, HR for PFS = 0.29; 95% CI = 0.11-0.78), while there were no significant relations with OS (HR = 0.83; 95% CI = 0.57-1.20) or PFS (HR = 0.85; 95% CI = 0.59-1.22) in patients with WHO grade IV glioma. In conclusion, use of metformin is associated with better overall and progression-free survival of patients with WHO grade III. Possible underlying mechanisms include the higher prevalence of IDH mutations in WHO grade III glioma, which might sensitize to the metabolic drug metformin.

KEYWORDS:

diabetes; glioma; metformin; survival

PMID:
30091464
DOI:
10.1002/ijc.31783
[Indexed for MEDLINE]

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