Researchers looked at whether exposure to metformin is associated with a decreased risk of bladder cancer….
Metformin works to decrease blood glucose by activating AMP-activated protein kinase (AMPK), which occurs through the reduction of mammalian target of rapamycin (mTOR) signaling. This mechanism is also known to inhibit cancer cell growth and proliferation, meaning metformin may have an additional benefit of reducing cancer risk. Bladder cancer is known to require activation of the mTOR pathway, making metformin ideal for this type of cancer. Previous observational studies have found metformin to be associated with a decreased risk of other cancers, including cancers of the breast, colon, liver, lung, pancreas, and prostate, though certain biases may have resulted in an exaggeration of these associations. As bladder cancer occurs more commonly in patients with T2DM and there is limited data regarding the relationship between metformin and bladder cancer, a study by Mamtani, R. et al. was developed to examine the risk of bladder cancer in new users of metformin and sulfonylureas among a cohort of patients with T2DM not previously using these medications.
This study was conducted using data from The Health Improvement Network (THIN), an electronic medical records database used in the UK. The database contains information for >10 million patients, making it ideal for rarer outcomes such as bladder cancer. This retrospective cohort study looked at patients that began using either metformin or a sulfonylurea between July 1, 2000 and August 31, 2010. Sulfonylureas were chosen as the comparator drugs in this study as they are used for first-line treatment of T2DM and prior studies have not shown them to have an association with bladder cancer or any other cancers. Inclusion criteria required that the patients be at least 40 years of age as diagnosis of bladder cancer before that age is likely due to another mechanism. The primary outcome for this study was an incident diagnosis of bladder cancer.
The final cohort included 87,600 patients, 71,742 initiating treatment with metformin and 16,128 initiating treatment with sulfonylureas. The results showed no difference in the incidence of bladder cancer in new users of metformin vs. new users of SU’s. There was also no observed association between the risk of bladder cancer and duration of metformin use relative to SU use. These findings differ from those found in previous studies that found a dramatic reduction in cancer risk with metformin use. The median follow-up time of this study was 2 years, and the data that was collected cannot exclude a protective effect of metformin in longer-term therapy. Also, though metformin was not found to have a preventative effect against bladder cancer in this study, future studies looking at the use of metformin as therapy in those with known bladder cancer may be beneficial, as inhibition of mTOR has been seen to have antitumor activity in patients with advanced bladder cancer.
- The results of this study do not show metformin to be associated with a decreased risk of bladder cancer in patients with T2DM.
- Further studies looking at metformin use in patients with advanced bladder cancer may be beneficial as inhibition of mTOR has been shown to have antitumor activity in this type of cancer.
Mamtani, R. et al. "Incidence of Bladder Cancer in Patients With Type 2 Diabetes Treated With Metformin or Sulfonylureas" Diabetes Care. 2014; 37(2):1-8.