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

Sep 24, 2026

Systematic review and meta-analysis searched MEDLINE, Embase, Web of Science, and Cochrane CENTRAL from 2011 to March 2021 to evaluate links between diabetes medications and breast, lung, colorectal, prostate, liver, and pancreatic cancer risk. Ninety-two studies (3 randomized trials, 64 cohorts, 25 case-control) involving 171 million participants were included, and 226 medication-class and cancer-site associations were analyzed. Biguanides and thiazolidinediones showed inverse or lower risks for several cancers, while insulin secretagogues and insulins were associated with increased pancreatic cancer risk.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Literature search and study selection

Study characteristics

Findings by medication class and cancer site

Biguanides

Thiazolidinediones

Insulins and insulin secretagogues

Overall conclusions

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Diabetes medications and cancer risk associations: a systematic review and meta‑analysis of evidence over the past 10 years Yixian Chen1*, Fidela Mushashi2, Surim Son3, Parveen Bhatti1,4, Trevor Dummer1 & Rachel A. Murphy1,4 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. Abbreviations AGIs Cochrane CENTRAL EMBASE HR MEDLINE NOS OR PRISMA PROSPERO RCT RR 95% CI Alpha-glucosidase inhibitors Cochrane Central Register of Controlled Trials Excerpta Medica DataBase Hazard ratio Medical Literature Analysis and Retrieval System Online Newcastle–Ottawa scale Odds ratio Preferred Reporting Items for Systematic Reviews and Meta-Analyses Prospective Register of Systematic Reviews Randomized controlled trial Relative risk 95% Confidence interval The prevalence of type II diabetes, herein referred to as diabetes, continues to grow and, globally, will affect 7.7%(439 million) of adults aged 20 to 79 years old by 20301. Epidemiological evidence suggests that diabetes is associated with a higher risk for many cancers, from 20 to 30% elevated breast or colorectal cancer to 97% elevated risk of intrahepatic cholangiocarcinoma or endometrial cancer2,3. These associations likely reflect shared etiology. For instance, tobacco use, physical inactivity, overweight, and poor diet are closely linked to cancer risk and progression4 and risk of diabetes5–7. Several biological mechanisms have been proposed to explain why diabetes 1School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada. 2BC Cancer, Vancouver, British Columbia, Canada. 3Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. 4Cancer Control Research, BC Cancer, Vancouver, British Columbia, Canada.*[email: ychen153@student.ubc.ca](email: ychen153@student.ubc.ca) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) may be associated with cancer, including inflammation, hyperglycemia, and hyperinsulinemia8,9. Furthermore, medications for diabetes may modify the association. Multiple epidemiologic studies have evaluated the association of diabetes medications with the risk of site-specific cancers in patients with diabetes10, 11. Previous systematic reviews either synthesized the effect of a single medication class on multiple cancer sites12–14 or the effects of multiple medication classes on overall cance

FAQs

Which databases and years were searched for the evidence in this review?

MEDLINE, Embase, Web of Science, and Cochrane CENTRAL were searched from 2011 to March 2021 for studies evaluating diabetes medications and cancer risk.

How many studies and participants were included in the systematic review?

A total of 92 studies were included: 3 randomized controlled trials, 64 cohort studies, and 25 case-control studies, involving 171 million participants.

What cancer-risk patterns were observed for biguanides and thiazolidinediones?

Biguanide use showed inverse relationships with colorectal and liver cancers, while thiazolidinediones were associated with lower risks of breast, lung, and liver cancers.

Sep 24, 2026

Uploaded by Maya Linwood