A study of over 172,000 diabetes patients found GLP-1 drugs don't increase or decrease colorectal cancer risk, but users had slightly more colonic polyps detected than DPP-4 inhibitor users.
OR = 0.99No difference in colorectal cancer risk between GLP-1 drug users and DPP-4 inhibitor users across 86,083 matched pairs
What the researchers found
In a propensity-score-matched study of 86,083 pairs of diabetes patients, GLP-1 receptor agonist users had no increased or decreased risk of colorectal cancer compared to DPP-4 inhibitor users (OR=0.99, 95% CI: 0.84–1.17). However, GLP-1RA users had a modestly higher incidence of colonic polyps (5.9% vs. 5.3%; OR=1.12, 95% CI: 1.08–1.17).
The polyp finding persisted even when patients with pre-existing polyps were excluded from the analysis, strengthening the signal. However, the absolute difference was small (0.6 percentage points), and colonic polyps are very common and usually benign.
Why it matters
With millions of people now taking GLP-1 drugs, understanding their long-term cancer risk is critical. Some earlier research suggested GLP-1 drugs might protect against colorectal cancer, while other studies raised concerns about tumor promotion. This large, well-designed study settles part of the debate — no cancer link — but raises a new question about colonic polyps that warrants monitoring.
The numbers in context
86,083 matched pairs · GLP-1RA vs DPP-4i · CRC: OR=0.99 (no difference) · Polyps: 5.9% vs 5.3% · OR=1.12 for polyps · 61 PS-matching variables · 2006–2021
How the study worked
Retrospective propensity-score-matched cohort study using a new-user, active comparator design (GLP-1RA vs DPP-4 inhibitors). Researchers matched 86,083 pairs using 61 variables to eliminate confounders. A secondary analysis excluded patients with baseline polyps. Data covered 2006–2021. Primary outcomes were incident colorectal cancer and colonic polyps.
Who was studied
172,166 adults with diabetes (86,083 matched pairs) who initiated either GLP-1 receptor agonists or DPP-4 inhibitors between 2006 and 2021
What this study cannot tell us
Retrospective observational design cannot prove causation. The higher polyp detection in GLP-1RA users could reflect detection bias — if GLP-1RA users had more colonoscopies (perhaps related to GI symptoms from the drug), more polyps would be found. The study compared GLP-1RA to DPP-4i, not to placebo or non-diabetic patients, so findings are relative to another active drug. Follow-up may be too short to capture slower-developing cancers.
How to read the evidence
This is a large, well-designed propensity-score-matched cohort study using an active comparator and 61 matching variables, providing strong observational evidence. However, as a retrospective study, it cannot establish causation.
When this study was published
Published in 2026 using data from 2006–2021. This is among the most current large-scale safety analyses of GLP-1 drugs and colorectal outcomes.
The bigger picture
This study joins a growing body of evidence examining GLP-1 drug safety as these medications become some of the most widely prescribed drugs in the world. The 'no cancer signal' finding is reassuring, but the modest polyp increase — while likely clinically insignificant — adds to the list of things that need long-term monitoring. As GLP-1 drug use expands to non-diabetic populations for weight loss, cardiovascular protection, and other off-label uses, cancer safety data becomes even more important.
Questions still open
- Is the higher polyp detection in GLP-1RA users a real biological effect or simply detection bias from more frequent colonoscopies?
- Would longer follow-up reveal a delayed cancer risk that this study's timeframe couldn't capture?
- Do different GLP-1 agonists (semaglutide vs. liraglutide vs. tirzepatide) have different effects on polyp formation?
Common questions
Do GLP-1 drugs cause colon cancer?
Should I be worried about the polyp finding?
Read the original research
GLP-1 receptor agonist initiation and risk of colorectal cancer and colonic polyps.
The American journal of the medical sciences
Citation
Moh'd Mari, Anwar Alshaakh; Alamin, Faris; Le, Minh Anh; Rizvi, Ali; Mansi, Ishak A. (2026). GLP-1 receptor agonist initiation and risk of colorectal cancer and colonic polyps.. The American journal of the medical sciences. https://doi.org/10.1016/j.amjms.2026.02.002