Metformin Associated With Lower Cancer Mortality in Type 2 Diabetes


  1. Gijs W.D. Landman, MD1,2,
  2. Nanne Kleefstra, MD2,3,
  3. Kornelis J.J. van Hateren, MD2,
  4. Klaas H. Groenier, PHD4,
  5. Rijk O.B. Gans, MD, PHD5 and
  6. Henk J.G. Bilo, MD, PHD, FRCP2,5
  1. 1Internal Medicine, Isala Clinics, Zwolle, the Netherlands;
  2. 2Diabetes Centre, Isala Clinics, Zwolle, the Netherlands;
  3. 3Medical Research Group, Langerhans, Zwolle, the Netherlands;
  4. 4General Practice, University Medical Center Groningen, Groningen, the Netherlands;
  5. 5Internal Medicine, University Medical Center Groningen, Groningen, the Netherlands.
  1. Corresponding author: Gijs W.D. Landman, g.w.d.landman{at}


OBJECTIVE Several studies have suggested an association between specific diabetes treatment and cancer mortality. We studied the association between metformin use and cancer mortality in a prospectively followed cohort.

RESEARCH DESIGN AND METHODS In 1998 and 1999, 1,353 patients with type 2 diabetes were enrolled in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study in the Netherlands. Vital status was assessed in January 2009. Cancer mortality rate was evaluated using standardized mortality ratios (SMRs), and the association between metformin use and cancer mortality was evaluated with a Cox proportional hazards model, taking possible confounders into account.

RESULTS Median follow-up time was 9.6 years, average age at baseline was 68 years, and average A1C was 7.5%. Of the patients, 570 died, of which 122 died of malignancies. The SMR for cancer mortality was 1.47 (95% CI 1.22–1.76). In patients taking metformin compared with patients not taking metformin at baseline, the adjusted hazard ratio (HR) for cancer mortality was 0.43 (95% CI 0.23–0.80), and the HR with every increase of 1 g of metformin was 0.58 (95% CI 0.36–0.93).

CONCLUSIONS In general, patients with type 2 diabetes are at increased risk for cancer mortality. In our group, metformin use was associated with lower cancer mortality compared with nonuse of metformin. Although the design cannot provide a conclusion about causality, our results suggest a protective effect of metformin on cancer mortality.


  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received July 28, 2009.
    • Accepted November 4, 2009.
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  1. Diabetes Care vol. 33 no. 2 322-326
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