Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16.
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.


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.
Landman
Gijs W D
GW
Internal Medicine, Isala Clinics, Zwolle, The Netherlands. g.w.d.landman@isala.nl
Kleefstra
Nanne
N
van Hateren
Kornelis J J
KJ
Groenier
Klaas H
KH
Gans
Rijk O B
RO
Bilo
Henk J G
HJ
D000368:Aged; D001794:Blood Pressure; D015992:Body Mass Index; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003925:Diabetic Angiopathies / Q000453:epidemiology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000401:mortality*; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin