Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes
- Design
- Retrospective cohort · 1651452 participants · Hard outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationType 2 diabetes; insulin comparator introduces confounding by diabetes severity; metformin comparison largely null.
- Could weight loss explain it?
- LikelyObesity-associated cancers; weight and glycaemic effects are plausible mediators; not analysed.
- Study tier
- Study tier 4Hypothesis-generating EHR cohort with a problematic comparator.
- Assessment
- Version 4 · Checked against the source by AI · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
In 1.65 million US patients with type 2 diabetes, GLP-1 users had lower rates of 10 of 13 obesity-related cancers than insulin users; there was no reduction for postmenopausal breast or thyroid cancer. Compared with metformin, GLP-1 drugs were linked to no lower risk of any cancer and to a higher risk of kidney cancer (HR 1.54, 95% CI 1.27-1.87). Observational; the insulin comparison may be confounded by diabetes severity (editorial note), and the authors call the findings preliminary.
01Findings
What the study reported
- Drugs
- Class unspecified
- Comparator
- insulin; metformin
- Primary outcome
- Incident diagnosis of 13 obesity-associated cancers over 15 years
- Effect
- vs insulin: HRs 0.35 (gallbladder) to 0.76 (kidney) for 10 of 13 cancers; no reduction for postmenopausal breast or thyroid cancer; vs metformin: no cancer reduced, kidney cancer increased (HR 1.54, 95% CI 1.27-1.87) (abstract)
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Not extracted
Who was studied
- Mean age
- 59.8
- Diabetes status
- type 2 diabetes required
- Sample size
- 1651452
Study quality details
- Study design
- Retrospective cohort
- Sample size
- 1651452
- Randomization
- no
- Blinding
- not stated
- Comparator
- insulin; metformin
- Follow up duration
- not stated
- Outcome type
- hard
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- large cohort
- Risk of bias
- confounding by indication (insulin users sicker); coded outcomes
- Funding conflicts
- no
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- NIH (NIA, NCI, NICHD)
- Industry funded
- No
- Manufacturer
- None identified
- Sponsor role
- no manufacturer funding identified
- Author conflicts
- Not available in metadata.
- Independent replication
- no
Funding is shown on every study and never used to score it.
03Claims
Claims this study bears on
- GLP-1 receptor agonists reduce the incidence of obesity-associated cancers.Mixed
In 1,651,452 US adults with type 2 diabetes, GLP-1 RAs versus insulin were associated with lower risk of 10 of 13 obesity-associated cancers (HRs 0.35 to 0.76) but not postmenopausal breast or thyroid cancer. Versus metformin, no cancer risk was significantly reduced and kidney cancer risk was higher (HR 1.54; 95% CI 1.27-1.87).
04Source
The source, as retrieved
Abstract
[IMPORTANCE] Thirteen human malignant neoplasms have been identified as obesity-associated cancers (OACs), ie, the presence of excess body fat is associated with increased risk of developing cancer and worse prognosis in patients with these specific tumors. The glucagon-like peptide receptor agonist (GLP-1RA) class of pharmaceuticals are effective agents for the treatment of type 2 diabetes (T2D) and for achieving weight loss, but the association of GLP-1RAs with the incident risk of 13 OACs is unclear. [OBJECTIVE] To compare the incident risk of each of the 13 OACs in patients with T2D who were prescribed GLP-1RAs vs insulins or metformin. [DESIGN, SETTING, AND PARTICIPANTS] This retrospective cohort study was based on a nationwide multicenter database of electronic health records (EHRs) of 113 million US patients. The study population included 1 651 452 patients with T2D who had no prior diagnosis of OACs and were prescribed GLP-1RAs, insulins, or metformin during March 2005 to November 2018. Data analysis was conducted on April 26, 2024. [EXPOSURES] Prescription of GLP-1RAs, insulins, or metformin. [MAIN OUTCOMES AND MEASURES] Incident (first-time) diagnosis of each of the 13 OACs occurring during a 15-year follow-up after the exposure was examined using Cox proportional hazard and Kaplan-Meier survival analyses with censoring applied. Hazard ratios (HRs), cumulative incidences, and 95% CIs were calculated. All models were adjusted for confounders at baseline by propensity-score matching baseline covariates. [RESULTS] In the study population of 1 651 452 patients with T2D (mean [SD] age, 59.8 [15.1] years; 827 873 [50.1%] male and 775 687 [47.0%] female participants; 5780 [0.4%] American Indian or Alaska Native, 65 893 [4.0%] Asian, 281 242 [17.0%] Black, 13 707 [0.8%] Native Hawaiian or Other Pacific Islander, and 1 000 780 [60.6%] White participants), GLP-1RAs compared with insulin were associated with a significant risk reduction in 10 of 13 OACs, including in gallbladder cancer (HR, 0.35; 95% CI, 0.15-0.83), meningioma (HR, 0.37; 95% CI, 0.18-0.74), pancreatic cancer (HR, 0.41; 95% CI, 0.33-0.50), hepatocellular carcinoma (HR, 0.47; 95% CI, 0.36-0.61), ovarian cancer (HR, 0.52; 95% CI, 0.03-0.74), colorectal cancer (HR, 0.54; 95% CI, 0.46-0.64), multiple myeloma (HR, 0.59; 95% CI, 0.44-0.77), esophageal cancer (HR, 0.60; 95% CI, 0.42-0.86), endometrial cancer (HR, 0.74; 95% CI, 0.60-0.91), and kidney cancer (HR, 0.76; 95% CI, 0.64-0.91). Although not statistically significant, the HR for stomach cancer was less than 1 among patients who took GLP-1RAs compared with those who took insulin (HR, 0.73; 95% CI, 0.51-1.03). GLP-1RAs were not associated with a reduced risk of postmenopausal breast cancer or thyroid cancer. Of those cancers that showed a decreased risk among patients taking GLP-1RAs compared with those taking insulin, HRs for patients taking GLP-1RAs vs those taking metformin for colorectal and gallbladder cancer were less than 1, but the risk reduction was not statistically significant. Compared with metformin, GLP-1RAs were not associated with a decreased risk of any cancers, but were associated with an increased risk of kidney cancer (HR, 1.54; 95% CI, 1.27-1.87). [CONCLUSIONS AND RELEVANCE] In this study, GLP-1RAs were associated with lower risks of specific types of OACs compared with insulins or metformin in patients with T2D. These findings provide preliminary evidence of the potential benefit of GLP-1RAs for cancer prevention in high-risk populations and support further preclinical and clinical studies for the prevention of certain OACs.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 38967919 first ingestion |