Diabetes medications and cancer risk associations: a systematic review and meta-analysis of evidence over the past 10 years

Diabetes medications may modify the risk of certain cancers. We systematically searched MEDLINE, Embase, Web of Science, and Cochrane CENTRAL from 2011 to March 2021 for studies evaluating associations between diabetes medications and the risk of breast, lung, colorectal, prostate, liver, and pancreatic cancers. A total of 92 studies (3 randomized controlled trials, 64 cohort studies, and 25 case-control studies) were identified in the systematic review, involving 171 million participants. Inverse relationships with colorectal (n=18; RR=0.85; 95% CI=0.78-0.92) and liver cancers (n=10; RR=0.55; 95% CI=0.46-0.66) were observed in biguanide users. Thiazolidinediones were associated with lower risks of breast (n=6; RR=0.87; 95% CI=0.80-0.95), lung (n=6; RR=0.77; 95% CI=0.61-0.96) and liver (n=8; RR=0.83; 95% CI=0.72-0.95) cancers. Insulins were negatively associated with breast (n=15; RR=0.90; 95% CI=0.82-0.98) and prostate cancer risks (n=7; RR=0.74; 95% CI=0.56-0.98). Positive associations were found between insulin secretagogues and pancreatic cancer (n=5; RR=1.26; 95% CI=1.01-1.57), and between insulins and liver (n=7; RR=1.74; 95% CI=1.08-2.80) and pancreatic cancers (n=8; RR=2.41; 95% CI=1.08-5.36). Overall, biguanide and thiazolidinedione use carried no risk, or potentially lower risk of some cancers, while insulin secretagogue and insulin use were associated with increased pancreatic cancer risk.