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

Abstract

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, and 25 case-control studies) were identified, involving 171 million participants. Inverse relationships with colorectal (RR = 0.85; 95% CI = 0.78–0.92) and liver cancers (RR = 0.55; 95% CI = 0.46–0.66) were observed in biguanide users. Thiazolidinediones were associated with lower risks of breast (RR = 0.87; 95% CI = 0.80–0.95), lung (RR = 0.77; 95% CI = 0.61–0.96) and liver (RR = 0.83; 95% CI = 0.72–0.95) cancers. Insulins were negatively associated with breast (RR = 0.90; 95% CI = 0.82–0.98) and prostate cancer risks (RR = 0.74; 95% CI = 0.56–0.98). Positive associations were found between insulin secretagogues and pancreatic cancer (RR = 1.26; 95% CI = 1.01–1.57), and between insulins and liver (RR = 1.74; 95% CI = 1.08–2.80) and pancreatic cancers (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.

Complications and comorbidities associated with antineoplastic chemotherapy: Rethinking drug design and delivery for anticancer therapy

“…By contrast, the effects of anti-diabetic therapies on cancer are controversial. According to a recent meta-analysis involving 171 million participants with diabetes, biguanide use is inversely related to colorectal and liver cancers, thiazolidinediones with lower risks of breast, lung, and liver cancers, and insulins with lower risks of breast and prostate cancer 159 . On the other hand, insulin secretagogues are positively associated with a higher risk of pancreatic cancer, and insulins with higher risks of liver and pancreatic cancers as well 159 .…”

“…According to a recent meta-analysis involving 171 million participants with diabetes, biguanide use is inversely related to colorectal and liver cancers, thiazolidinediones with lower risks of breast, lung, and liver cancers, and insulins with lower risks of breast and prostate cancer 159 . On the other hand, insulin secretagogues are positively associated with a higher risk of pancreatic cancer, and insulins with higher risks of liver and pancreatic cancers as well 159 . Besides, the effect of metformin on cancer is also contentious, with some research showing protective and anticancer effects against several cancers in addition to its anti-diabetic efficacy, others demonstrating no significant difference 160 , 161 , 162 .…”

Drug repositioning in thyroid cancer treatment: the intriguing case of anti-diabetic drugs

“…According to data from several meta-analyses, an overall increased cancer risk was reported in patient using sulfonylureas compared with those treated with metformin or other diabetes medications (Wu et al, 2015;Sacks et al, 2018;Mekuria et al, 2019;Chen Y. et al, 2023b). A meta-analysis of 8 studies (3 cohort studies, 3 case-control studies and 2 clinical trials) failed to demonstrate any association between glinides and risk of cancer (Wu et al, 2015).…”

The interplay between antidiabetic medications and cancer risk

“…Diabetes and cancer share common risk factors such as tobacco use, physical inactivity, obesity, and poor diet. 3 These factors intertwine to heighten the risk of various cancers. A higher prevalence of type II diabetes coupled with its shared etiology with cancer underlines the importance of understanding the impact of ADMs on cancer risk.…”