Association between metformin use and progression of monoclonal gammopathy of undetermined signifi cance to multiple myeloma in US veterans with diabetes mellitus: A population-based retrospective cohort study

Su Hsin Chang*, Suhong Luo, Katiuscia K. O'Brian, Theodore S. Thomas, Graham A. Colditz, Nils P. Carlsson, Kenneth R. Carson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Background: Multiple myeloma is one of the most common haematological malignancies in the USA and is consistently preceded by monoclonal gammopathy of undetermined signifi cance (MGUS). We aimed to assess the association between metformin use and progression of MGUS to multiple myeloma. Methods: We did a retrospective cohort study of patients registered in the US Veterans Health Administration database and diagnosed with MGUS between Oct 1, 1999, and Dec 31, 2009. We included patients (aged >18 years) with at least one International Classifi cation of Diseases (9th revision) code for diabetes mellitus and one treatment for their diabetes before MGUS diagnosis. We reviewed patient-level clinical data to verify diagnoses and extract any available data for size of baseline M-protein and type of MGUS. We defi ned metformin users as patients with diabetes who were given metformin consistently for 4 years after their diabetes diagnosis and before multiple myeloma development,death, or censorship. Our primary outcome was time from MGUS diagnosis to multiple myeloma diagnosis. We used Kaplan-Meier curves and Cox models to analyse the association between metformin use and MGUS progression. Findings: We obtained data for 3287 patients, of whom 2003 (61%) were included in the fi nal analytical cohort. Median follow-up was 69 months (IQR 49-96). 463 (23%) participants were metformin users and 1540 (77%) participants were non-users. 13 (3%) metformin users progressed to multiple myeloma compared with 74 (5%) non-users. After adjustment, metformin use was associated with a reduced risk of progression to multiple myeloma (hazard ratio 0.47, 95% CI 0.25-0.87). Interpretation: For patients with diabetes diagnosed with MGUS, metformin use for 4 years or longer was associated with a reduced risk of progression of MGUS to multiple myeloma. Prospective studies are needed to establish whether this association is causal and whether these results can be extrapolated to non-diabetic individuals.

Original languageEnglish (US)
Pages (from-to)e30-e36
JournalThe Lancet Haematology
Volume2
Issue number1
DOIs
StatePublished - 2015

Funding

The Barnes-Jewish Hospital Foundation and the National Institutes of Health ( grant U54-CA155496 ) supported this research. S-HC is supported by an Agency for Healthcare Research and Quality grant ( K01-HS022330 ). GAC is supported by a professorship from the American Cancer Society Clinical Research. KRC is supported by an American Cancer Society grant ( MSRG-13-077-01-CPHPS ). The conclusions and opinions presented herein are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health, the Agency for Healthcare Research and Quality, the American Cancer Society, or the Barnes-Jewish Hospital Foundation. We thank Michael Tomasson (Oncology Division, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA) for his valuable inputs to the writing of this manuscript.

ASJC Scopus subject areas

  • Hematology

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