Lower Risk of Cancer in Patients on Metformin in Comparison With Those on Sulfonylurea Derivatives Results from a large population-based follow-up study

Rikje Ruiter; Loes E. Visser; Myrthe P.P. van Herk-Sukel; Jan-Willem W. Coebergh; Harm R. Haak; Petronella H. Geelhoed-Duijvestijn; Sabine M.J.M. Straus; Ron M.C. Herings; Bruno H.Ch. Stricker

doi:10.2337/dc11-0857

Lower Risk of Cancer in Patients on Metformin in Comparison With Those on Sulfonylurea Derivatives

Results from a large population-based follow-up study

Rikje Ruiter, MD¹,²,
Loes E. Visser, PHARMD¹,³,⁴,
Myrthe P.P. van Herk-Sukel, MSC⁵,
Jan-Willem W. Coebergh, MD, PHD⁶,
Harm R. Haak, MD, PHD⁷,
Petronella H. Geelhoed-Duijvestijn, MD, PHD⁸,
Sabine M.J.M. Straus, MD, PHD⁹,¹⁰,
Ron M.C. Herings, MD, PHD⁵,¹¹ and
Bruno H.Ch. Stricker, MB, PHD¹,²,⁴,¹⁰ ⇓

¹Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands
²Drug Safety Unit, Inspectorate of Health Care, The Hague, the Netherlands
³Department of Hospital Pharmacy, Erasmus MC, Rotterdam, the Netherlands
⁴Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands
⁵PHARMO Institute for Drug Outcomes Research, Utrecht, the Netherlands
⁶Department of Public Health, Erasmus MC, Rotterdam, the Netherlands
⁷Department of Internal Medicine, Maxima Medical Centre, Eindhoven, the Netherlands
⁸Department of Internal Medicine, Medical Centre Haaglanden, The Hague, the Netherlands
⁹Dutch Medicines Evaluation Board, The Hague, the Netherlands
¹⁰Department of Medical Informatics, Erasmus MC, Rotterdam, the Netherlands
¹¹Department of Health Policy & Management, Erasmus MC, Rotterdam, the Netherlands

Corresponding author: Bruno H.Ch. Stricker, b.stricker{at}erasmusmc.nl.

Abstract

OBJECTIVE Numerous studies have suggested a decreased risk of cancer in patients with diabetes on metformin. Because different comparison groups were used, the effect magnitude is difficult to estimate. Therefore, the objective of this study was to further analyze whether, and to what extent, use of metformin is associated with a decreased risk of cancer in a cohort of incident users of metformin compared with users of sulfonylurea derivatives.

RESEARCH DESIGN AND METHODS Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. The association between the risk of cancer in those using metformin compared with those using sulfonylurea derivatives was analyzed using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant.

RESULTS Use of metformin was associated with a lower risk of cancer in general (hazard ratio 0.90 [95% CI 0.88–0.91]) compared with use of sulfonylurea derivatives. When specific cancers were used as end points, similar estimates were found. Dosage-response relations were identified for users of metformin but not for users of sulfonylurea derivatives.

CONCLUSIONS In our study, cumulative exposure to metformin was associated with a lower risk of specific cancers and cancer in general, compared with cumulative exposure to sulfonylurea derivatives. However, whether this should indeed be seen as a decreased risk of cancer for the use of metformin or as an increased risk of cancer for the use sulfonylurea derivatives remains to be elucidated.

Footnotes

This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-0857/-/DC1.

Received May 6, 2011.
Accepted October 11, 2011.

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