GLP-1 Drugs and Cancer in Older Diabetics: No Overall Risk, But Kidney and Endometrial Signals | Research

The takeaway

In a Medicare study of over 42,000 matched patients, GLP-1 drugs showed no increased overall cancer risk versus other diabetes drugs, but flagged possible elevated risks for kidney cancer (43% higher) and endometrial cancer (55% higher).

Overall cancer risk: neutral
GLP-1 drugs showed no increased overall cancer risk versus two other diabetes drug classes — but kidney (HR 1.43) and endometrial (HR 1.55) cancer signals warrant further investigation

What the researchers found

In the GLP-1 RA versus SGLT2i matched cohort (21,362 pairs), overall cancer risk was not significantly different (HR 1.03; 95% CI: 0.95-1.12). However, GLP-1 RA users had significantly increased kidney cancer risk (HR 1.43; 95% CI: 1.06-1.92).

In the GLP-1 RA versus DPP4i matched cohort (20,962 pairs), overall cancer risk was again not different (HR 0.96; 95% CI: 0.89-1.04). However, endometrial cancer risk was significantly elevated (HR 1.55; 95% CI: 1.01-2.37). The nine cancers analyzed were thyroid, pancreatic, bladder, colorectal, lung, kidney, breast, endometrial, and prostate — all considered obesity-associated cancers.

Why it matters

With tens of millions of older adults taking GLP-1 drugs, even small increases in specific cancer risks could affect many people. This well-designed Medicare study provides reassurance that overall cancer risk is not elevated, which is important for both patients and prescribers. The kidney and endometrial cancer signals, while requiring confirmation, offer specific targets for enhanced surveillance — a much more useful finding than a vague overall cancer concern.

How the study worked

Retrospective cohort study using 2013-2020 national Medicare claims data. Researchers identified cancer-naïve patients with type 2 diabetes who initiated GLP-1 RAs, SGLT2 inhibitors, or DPP4 inhibitors. Propensity score matching (1:1) was used to create balanced comparison groups, adjusting for confounders. Cox proportional hazards models estimated hazard ratios for nine obesity-associated cancers individually and overall.

What this study cannot tell us

This is a retrospective observational study based on Medicare claims, which may have coding inaccuracies and cannot capture all confounders. The kidney and endometrial cancer signals each came from only one of the two comparisons, raising the possibility of chance findings given multiple comparisons. Medicare patients are older, so findings may not apply to younger GLP-1 drug users. The follow-up period (2013-2020) may not be long enough to capture slow-growing cancers. Specific GLP-1 drug types within the class were not analyzed separately.

How to read the evidence

This is a large retrospective cohort study using national Medicare data with propensity score matching — a strong observational design. The large sample sizes and active comparator design provide robust evidence for overall cancer safety. The site-specific signals (kidney, endometrial) are statistically significant but need independent replication.

When this study was published

Published in 2025 using 2013-2020 Medicare data, this is a very current safety analysis reflecting real-world use of GLP-1 drugs in the older diabetic population during the period of rapid adoption.

The bigger picture

This study adds nuance to the GLP-1 cancer risk debate. While other studies have flagged colorectal or thyroid cancer concerns, this large Medicare analysis found no signal for either. The kidney and endometrial cancer signals are novel and biologically plausible — both cancers are influenced by metabolic and hormonal pathways that GLP-1 drugs may modulate. The use of active comparators (SGLT2i, DPP4i) rather than non-users makes confounding by disease less likely, strengthening the cancer-specific signals even though overall risk is neutral.

Questions still open

Is the kidney cancer signal related to GLP-1 receptor expression in the kidneys, or could it reflect detection bias from increased medical monitoring?
Does the endometrial cancer risk differ by specific GLP-1 drug, dose, or duration of use?
Would these cancer signals persist in younger populations or in patients using GLP-1 drugs for obesity rather than diabetes?

Common questions

Should I worry about cancer if I'm taking a GLP-1 drug?

This large Medicare study found no increase in overall cancer risk — which is reassuring. Two specific cancers (kidney and endometrial) showed modest increases that need further study before drawing conclusions. The most practical takeaway: stay current on recommended cancer screenings, and if you have risk factors for kidney or endometrial cancer, discuss monitoring with your doctor.

Why might GLP-1 drugs affect kidney or endometrial cancer risk specifically?

Both the kidneys and uterus have GLP-1 receptors and are sensitive to metabolic and hormonal changes. GLP-1 drugs cause significant shifts in insulin, glucose, and other metabolic signals that could theoretically influence cell growth in these organs. However, it's also possible that these signals reflect detection bias (more medical monitoring catches more cancers) or residual confounding rather than a true drug effect. More research is needed to understand whether there's a causal connection.

Read the original research

Association of Glucagon-Like Peptide-1 Receptor Agonists With Cancer Risk in Older Adults With Type 2 Diabetes.

Obesity (Silver Spring, Md.)

View on PubMed ↗Publisher’s paper ↗

Citation

Lu, Ying; Dai, Hao; Tang, Huilin; Donahoo, William T; George, Thomas J; Sun, Ramon C; Jiang, Sizun; Tan, Aik Choon; Guo, Yi; Licht, Jonathan D; Allen, John M; Lee, Kelvin P; Guo, Jingchuan; Bian, Jiang. (2025). Association of Glucagon-Like Peptide-1 Receptor Agonists With Cancer Risk in Older Adults With Type 2 Diabetes.. Obesity (Silver Spring, Md.). https://doi.org/10.1002/oby.24366