Obesity, Cancer Risk & the GLP-1 Conversation: What Science Is Really Saying

Obesity has long been recognized as a major risk factor for multiple cancers. A growing body of research shows that excess adipose tissue is metabolically active, reshaping the inflammatory, hormonal, and metabolic environment in ways that can promote tumor development. Chronic inflammation, insulin resistance, and hormonal dysregulation together create conditions that favor tumorigenesis.

Understanding these mechanisms is essential as the global conversation around GLP-1 receptor agonists (GLP-1RAs) accelerates. These drugs, widely known for their weight-loss effects, are now raising important questions about their potential role in reducing cancer risks.

How Obesity Drives Cancer Biology

Obesity represents a profound metabolic disturbance. Adipose tissue (body fat) is now understood to function as an endocrine and immunologically active organ, rather than as a passive energy storage depot.

As fat depots expand with obesity, enlarged adipocytes (fat cells) become stressed or hypoxic, triggering the release of chemokines that recruit immune cells, particularly macrophages, into adipose tissue. These immune cells release pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β [1], contributing to a chronic, low-grade inflammatory state that can damage DNA, weaken immune surveillance, and activate pro-survival signaling pathways such as NF-κB in emerging tumor cells [2].

Insulin resistance, a hallmark of obesity, further amplifies this risk. Elevated insulin and insulin-like growth factor-1 (IGF-1) stimulate receptors on many tumor types, activating PI3K/Akt and MAPK signaling pathways that drive proliferation and inhibit apoptosis. This mechanism is particularly relevant in cancers strongly associated with obesity, including colorectal, breast, and endometrial cancers [3].

Hormonal imbalances further amplify risk; adipose tissue contains high levels of aromatase, an enzyme that converts androgens into estrogens. Increased estrogen exposure can fuel the development of hormone-sensitive cancers, particularly in post-menopausal women.

Adipokines, hormone-like signaling molecules released by adipose tissue, also play a role. One of the most prominent, leptin, promotes angiogenesis and metastatic signaling, while reduced adiponectin weakens anti-tumor responses and increases tissue susceptibility to carcinogenic stress [4].

This biological framework helps explain the growing interest in GLP-1RAs and their potential effects beyond weight loss.

The GLP-1 Conversation

GLP-1RAs such as semaglutide and liraglutide produce substantial weight loss — often around 15-20% of body weight while treatment is maintained [5]. They work by mimicking gut hormone GLP-1, which signals satiety to the brain, slows gastric emptying, and helps regulate glucose metabolism. Beyond their effects on weight, they also improve metabolic health by restoring insulin sensitivity and reducing systemic inflammation.

These metabolic improvements are highly relevant to cancer biology. By lowering circulating insulin and insulin-like growth factor-1 (IGF-1; a hormone that promotes cell growth and survival), GLP-1RAs can dampen proliferative signaling pathways linked to tumor growth. At the same time, reductions in adipose tissue help normalize adipokine profiles, and decrease inflammatory cytokine production.

Emerging clinical data reinforces this possibility. Large observational studies and analyses of cardiovascular outcome trials — including extensions of the SELECT study, a large clinical trial evaluating semaglutide in people with overweight or obesity and cardiovascular disease — suggest lower incidence rates of several obesity-related cancers among GLP-1RA users. Some analyses report hazard ratios in the range of 0.7-0.9, indicating a roughly 10-30% lower risk compared with non-users [6].

These observations align with what is known about the biological consequences of obesity. As adipose tissue expands, parts of it can become poorly supplied with oxygen. This activates hypoxia-inducible factor-1α (HIF-1α), a cellular oxygen-sensing protein that helps cells adapt to hypoxic conditions by shifting metabolism toward glycolysis and activating survival pathways. These adaptations can also help premalignant cells tolerate low-oxygen environments and contribute to the acidic microenvironments commonly observed in solid tumors [7].

Elevated leptin levels, which increase with fat mass, can also stimulate signaling pathways that promote tumor growth, blood vessel formation, and cellular migration. Hyperglycemia adds another layer of stress, generating reactive metabolic byproducts that amplify inflammation and tissue damage, further supporting tumor progression.

By reducing adiposity, improving glycemic control, and lowering systemic inflammation, GLP-1RAs may help interrupt several of these obesity-driven processes that can create a tumor-promoting environment [8].

Benefits and Limitations

The potential advantages of GLP-1RAs in cancer risk reduction stem from their ability to address multiple drivers of tumorigenesis simultaneously. Recent studies consistently show 20-40% lower incidence of obesity-linked cancers (e.g., colorectal, endometrial) in GLP-1RA users versus controls, with emerging data from trials reinforcing preventive potential in high-risk groups [9].

Weight loss reduces adipose-driven inflammation and hormonal imbalance. Improved insulin sensitivity lowers hyperinsulinemia, removing a key proliferative signal for many cancers [8]. Some experimental studies also suggest that GLP-1 signaling may directly suppress inflammatory pathways such as NF-κB, further reducing pro-tumorigenic signaling.

Yet these drugs are not a universal solution. Not all cancers respond equally to metabolic changes, and long-term outcomes remain under investigation. Practical barriers also remain. Responses to GLP-1RAs vary between individuals, weight loss typically plateaus over time, and the metabolic benefits of GLP-1RAs are also closely tied to continued treatment, as discontinuation is frequently associated with partial weight regain and attenuation of metabolic improvements. Pharmacological intervention alone cannot address the broader drivers of metabolic disease, including diet quality, physical inactivity, and long-standing metabolic dysfunction.

A Broader Perspective on Cancer Prevention

The growing interest in GLP-1RAs reflects a broader shift in how we think about cancer risk. Metabolic health is increasingly recognized as a central component of cancer prevention, and GLP-1RAs may help address several of the biological drivers that link obesity to tumor development [10].

Weight management, whether achieved through lifestyle changes, pharmacological interventions, or a combination of both, can meaningfully reduce many of the conditions that support tumor development. Yet it represents only one component of a broader prevention strategy.

Smoking cessation, regular physical activity, fiber-rich diets, and early screening remain essential pillars of cancer risk reduction. Even after substantial weight loss, the inflammatory and metabolic imprint of long-standing obesity may persist for years.

GLP-1RAs therefore represent powerful tools, but not silver bullets. Their true value may lie in complementing broader efforts to improve metabolic health and reshape the biological environments in which cancer emerges.

References:

1. da Cruz Nascimento, S. S., Carvalho de Queiroz, J. L., Fernandes de Medeiros, A., de Franca Nunes, A. C., Piuvezam, G., Lima Maciel, B. L., … & Morais, A. H. D. A. (2022). Anti-inflammatory agents as modulators of the inflammation in adipose tissue: A systematic review. PLoS One , 17 (9), e0273942. doi: https://doi.org/10.1371/journal.pone.0273942

2. Zhao, Y., Ye, X., Xiong, Z., Ihsan, A., Ares, I., Martínez, M., … & Martínez, M. A. (2023). Cancer metabolism: the role of ROS in DNA damage and induction of apoptosis in cancer cells. Metabolites , 13 (7), 796. doi: https://doi.org/10.3390/metabo13070796

3. Bizimana Rukundo, T. Insulin/IGF Signaling Pathways as Shared Drivers in Obesity, Type 2 Diabetes, and Tumorigenesis. doi: https://doi.org/10.59298/NIJSES/2025/63.143150

4. Bocian-Jastrzębska, A., Malczewska-Herman, A., & Kos-Kudła, B. (2023). Role of leptin and adiponectin in carcinogenesis. Cancers , 15 (17), 4250. doi: https://doi.org/10.3390/cancers15174250

5. Reiss, A. B., Gulkarov, S., Lau, R., Klek, S. P., Srivastava, A., Renna, H. A., & De Leon, J. (2025). Weight Reduction with GLP-1 Agonists and Paths for Discontinuation While Maintaining Weight Loss. Biomolecules , 15 (3), 408. doi: https://doi.org/10.3390/biom15030408

6. Im, C., Qin, N., Wang, Z., Qiu, W., Howell, C. R., Sapkota, Y., … & Yasui, Y. (2020). Generalizability of “GWAS Hits” in clinical populations: lessons from childhood cancer survivors. The American Journal of Human Genetics , 107 (4), 636-653.

7. Zhang, H., Li, S., Wang, D., Liu, S., Xiao, T., Gu, W., … & Chen, P. (2024). Metabolic reprogramming and immune evasion: the interplay in the tumor microenvironment. Biomarker research , 12 (1), 96. doi: https://doi.org/10.1186/s40364-024-00646-1

8. Chimera, B. (2025). Health Effects of Dietary Diversity: Exploration through Cancer Risk, Metabolomic Signatures and Microbiome Diversity (Doctoral dissertation, Université Claude Bernard-Lyon I).

9. Xu, Y. X. Z., & Mishra, S. (2018). Obesity-linked cancers: current knowledge, challenges and limitations in mechanistic studies and rodent models. Cancers , 10 (12), 523. doi: https://doi.org/10.3390/cancers10120523

10. Miousse, I. R. (2025). GLP-1 receptor agonists in the context of cancer: the road ahead. American Journal of Physiology-Cell Physiology , 328 (6), C1822-C1828.

Jacek Antas

Chief Executive Officer

Jacek Antas is a shareholder of the Company, has spent more than 25 years in the financial services industry holding various positions in sales and consulting.

Mr. Antas obtained a master’s degree from the Warsaw School of Economics and has served as a board member of various
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Mr. Murphy is a certified public accountant with over thirty years of experience in finance and operations management. He is currently a consultant with Danforth Advisors LLC (“Danforth”), a leading provider of outsourced strategic and operational specialists across functions in the life sciences industry. While at Danforth, Mr. Murphy has served over fifteen private and publicly held life sciences companies as CFO and CFO Advisor, helping them secure over USD 0.5 billion in financing and successfully execute pivotal asset transactions. Mr. Murphy functions as a consultant to Helix pursuant to a consulting agreement between the Company and Danforth.

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Thomas Mehrling

Medical Adviser

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Brenda is the Clinical Operations Director at Helix Biopharma Corp. A clinical research operations professional with 25 years of experience managing clinical trials, ranging from early Phase I to late Phase IIIb/IV studies, she brings experience in clinical study protocol writing and development, trial start-up and vendor management, and a proven track record in planning and managing clinical trials to quality standards, timelines and budget. Brenda joined Helix Biopharma Corp. in 2018, working to advance the clinical program of L-DOS47. She holds B.Sc and M.Sc. degrees from the University of Toronto, specializing in Nutritional Sciences and Human Biology.

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Chairman of the Board

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Mr. Antas obtained a master’s degree from the Warsaw School of Economics and has served as a board member of various
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Jonathan Davis

Advisor, ADC Discovery

Jonathan Davis received his Ph.D. from University of California, San Francisco, where he studied protein structure and function using NMR. After a post-doc at Harvard Medical School exploring RNA selection and structure in the labs of Jack Szostak and Gerhard Wagner, he went to work at EMD Serono, where his work involved improving antibody-based therapeutics, inventing a platform technology for generating heterodimeric Fcs as a basis for multifunctional molecules, and developing a novel scaffold based on an artificially-designed protein from David Baker’s lab. In 2008 he took a job at Bristol-Myers Squibb in Waltham/Cambridge MA, working on antibody discovery and platform development in a wide range of therapeutic areas, with a particular focus on multispecific therapeutics. He moved to Madison, WI in 2019 to take on the role of VP of Innovation and Strategy at Invenra, a biotech focused on bispecific antibodies, and where he is currently head of the Scientific Advisory Board. In early 2024 he left the corporate world to found Creative Antibodies, a consulting firm that helps guide companies to successful antibody discovery and development projects, from mAbs to multispecifics, ADCs, and other formats. Outside of science, Jonathan is a conservatory trained cellist, plays numerous other instruments, and founded the UCSF Orchestra (now Symphony Parnassus) in San Francisco, where he was Music Director for six years.

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Davide graduated as a pharmacist and received his PhD in Pharmaceutical Technology and Biotechnology from the University of Vienna. He has over 20 years of experience in the pharmaceutical industry, principally in the field of oncology. At the beginning of his career, Davide led oncology business units and commercial departments at Mundipharma and Gilead across Austria and Eastern Europe. Since over 10 years he has been working as a CMC expert, covering operational and regulatory CMC functions on behalf of over 20 different small- and medium-sized biotech companies across the world. He has served as CMC Director and CSO/CTO for several years, developing both small molecules and biologics (mABs, Fab, ADCs and Radio-immuno-conjugates) from early discovery to NDA/BLA in the US, EU and Canada, with a focus on First-in-Human and Phase I/II studies in oncology indications.

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