GLP-1s: Weight Loss Drugs—or Cancer Fighters?
With GLP-1s dominating so much airtime these days, it made sense for me to attend the ‘GLP-1 RA and Cancer’ session during my time at SGO 2026. This introductory talk provided a crucial refresher on the mechanism of GLP-1s, emphasising their systemic effects.
The key takeaway was that these drugs have profound anti-inflammatory and immune-modulating properties that occur independently of weight loss or glucose control.
They act on receptors found on immune cells (monocytes, T-cells, etc.), decreasing inflammatory cytokines (TNF-alpha, NF-kappa-beta) and promoting an anti-inflammatory cellular environment. This provides a strong biological rationale for their use in cancer, a disease driven by inflammation.
Two notable preclinical studies from the University of North Carolina provided strong evidence of direct anti-tumour effects in mouse models of obesity-driven endometrial cancer:
- Retatrutide (Triple Agonist): significantly reduced tumour weight by over 80% in obese mice. Crucially, it also reduced tumour weight by over 50% in lean mice, demonstrating a powerful anti-tumour effect that is not solely dependent on weight loss. The mechanism was linked to decreased cell proliferation (Ki67) and inhibition of the mTOR pathway1.
- Tirzepatide (Dual Agonist) vs. Intermittent Energy Restriction (IER): the study found that while IER was more effective for weight loss, both IER and Tirzepatide were equally effective at reducing tumour size (~70% reduction). This again reinforces the concept that the anti-cancer effect is not just a by-product of weight reduction. The study also showed that Tirzepatide significantly remodelled the gut microbiome, promoting beneficial bacteria associated with better glucose control and lower inflammation2.
There was also discussion about the role of GLP-1s as preventative agents.
The TriNetX Database Study was a retrospective study using the large TriNetX EHR database, which provided the first major cohort of real-world evidence for the clinical benefit of GLP-1s in endometrial cancer management3.
In young patients (<45yrs) with endometrial intraepithelial neoplasia (EIN) or endometrial cancer undergoing fertility-sparing management with progestins, the addition of a GLP-1 was associated with a 66% reduction in the risk of progressing to hysterectomy at six months.
This provides strong, hypothesis-generating evidence that GLP-1s can act as a powerful adjunctive therapy, potentially improving the efficacy of standard hormonal treatments and helping more patients preserve their fertility.
GLP-1s were framed as a potential new pillar of endometrial cancer therapy, particularly as an adjunctive or preventative strategy.
What next?
The session concluded by highlighting the two biggest challenges:
- Engaging pharma: How to make gynaecological cancer a priority for the pharmaceutical companies developing these GLP-1 blockbuster drugs?
- Payer access: How to get insurance companies to cover these expensive drugs for cancer-related indications?
The consensus was that generating more robust data—both from prospective clinical trials and large-scale real-world evidence studies—is the only way to overcome these hurdles.
To find out more about Ipsos’ real-world data in the Oncology and GLP-1 space, contact [email protected]
References
1. Singleton, M. et al. (2026) ‘The triple agonist incretin mimetic retatrutide as a novel treatment strategy for obesity-driven endometrial cancer’, SGO 2026 Annual Meeting on Women’s Cancer, San Juan, Puerto Rico, April 10-13th 2026
2. Diggs, A. et al. (2026) ‘Tirzepatide and Intermittent Energy Restriction have anti-obesity and anti-tumorigenic effects in a pre-clinical mouse model of obesity-driven endometrial cancer’, SGO 2026 Annual Meeting on Women’s Cancer, San Juan, Puerto Rico, April 10-13th 2026
3. Hsieh, T.Y.J et al. (2026) ‘Impact of GLP-1 RA plus Progestin Therapy on Conservative Management of Endometrial Cancer and Endometrial Intraepithelial Neoplasia’, SGO 2026 Annual Meeting on Women’s Cancer, San Juan, Puerto Rico, April 10-13th 2026
