Incidence of bladder cancer in patients with type 2 diabetes treated with metformin or sulfonylureas.
OBJECTIVE
Previous studies evaluating the effect of metformin on cancer risk have been impacted by time-related biases. To avoid these biases, we examined the incidence of bladder cancer in new users of metformin and sulfonylureas (SUs).


METHODS
This cohort study included 87,600 patients with type 2 diabetes in The Health Improvement Network database. Use of metformin or an SU was treated as a time-dependent variable. Cox regression-generated hazard ratios (HRs) compared metformin use with SU use, adjusted for age, sex, smoking, obesity, and HbA1c level.


RESULTS
We identified 196 incident bladder cancers in the metformin cohort and 66 cancers in the SU cohort. Use of metformin was not associated with decreased bladder cancer risk (HR 0.81 [95% CI 0.60-1.09]). This association did not differ by sex (P for interaction = 0.20). We observed no association with duration of metformin relative to SU use (3 to <4 years of use: 0.57 [0.25-1.34]; 4 to <5 years of use: 0.93 [0.30-2.85; ≥5 years of use: 1.18 [0.44-3.19]; P for trend = 0.26).


CONCLUSIONS
Use of metformin is not associated with a decreased incidence of bladder cancer. Similar methods should be used to study other cancers that have previously been identified as potentially preventable with metformin.
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA ronac.mamtani@uphs.upenn.edu.
Ronac
R
Mamtani
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
Nick
N
Pfanzelter
Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.
Kevin
K
Haynes
Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.
Brian S
BS
Finkelman
Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.
Xingmei
X
Wang
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
Stephen M
SM
Keefe
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
Naomi B
NB
Haas
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
David J
DJ
Vaughn
Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA.
James D
JD
Lewis
D000368:Aged; D015331:Cohort Studies; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000473:pathology; D012189:Retrospective Studies; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology*
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin