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Major Trial to Test Drugs Like Ozempic for Cancer Prevention

cancer

A groundbreaking initiative in the UK aims to offer weight-loss injections, such as Ozempic, Wegovy, and Mounjaro, to tens of thousands of patients as a preventive measure against cancer. This follows compelling research indicating that these drugs, known as glucagon-like peptide-1 receptor agonists (GLP-1RAs), may significantly reduce the risk of obesity-related cancers and potentially other cancer types. A large-scale clinical trial, led by the University of Manchester and funded by Cancer Research UK, is set to explore whether these medications can serve as a transformative tool in combating rising cancer rates, potentially mirroring the preventive use of statins for heart disease.

Background on GLP-1 Drugs

GLP-1 receptor agonists, originally developed for type 2 diabetes management, mimic the GLP-1 hormone, which regulates blood sugar, slows gastric emptying, and suppresses appetite. This mechanism leads to significant weight loss, with drugs like tirzepatide (Mounjaro/Zepbound) achieving up to 20.2% body weight reduction compared to 13.7% for semaglutide (Wegovy) in clinical trials. Approved for obesity treatment since 2021 (semaglutide) and 2022 (tirzepatide), these medications have gained popularity for their efficacy in weight management and additional health benefits, including reduced cardiovascular and kidney disease risks.

Research on Cancer Risk Reduction

Recent studies have highlighted the potential of GLP-1 drugs to lower the risk of obesity-related cancers, which include 13 types such as breast, colorectal, endometrial, pancreatic, and liver cancers. A pivotal study presented at the European Congress on Obesity in Malaga, Spain, and published in eClinicalMedicine, analyzed 6,356 adults with obesity and type 2 diabetes over a median of 7.5 years. It compared cancer incidence in patients treated with first-generation GLP-1RAs (e.g., liraglutide, exenatide) versus those who underwent bariatric surgery, a known intervention for reducing cancer risk by 30–42%.

The study found similar rates of obesity-related cancers (148 cases in 3,178 GLP-1 patients vs. 150 in 3,178 surgery patients), despite bariatric surgery’s greater weight loss (approximately double that of GLP-1 drugs). After adjusting for weight loss differences, GLP-1RAs were associated with a 41% lower relative risk of obesity-related cancers compared to surgery. Researchers, including Dr. Yael Wolff Sagy from Clalit Health Services, Israel, attributed this to mechanisms beyond weight loss, such as reduced systemic inflammation, a known cancer risk factor.

Additional retrospective studies support these findings. A 2024 analysis of over 1.65 million type 2 diabetes patients in the TriNetX database showed that GLP-1RAs reduced the risk of 10 out of 13 obesity-associated cancers compared to insulin, with significant reductions in gastrointestinal cancers (e.g., 44% lower colorectal cancer risk). Another study in JAMA Oncology found GLP-1RAs linked to lower colorectal cancer risk in diabetes patients, particularly those with obesity, suggesting both weight-dependent and independent protective effects.

However, not all cancers showed reduced risk. GLP-1RAs did not significantly lower breast, thyroid, or stomach cancer risks compared to insulin or metformin, and one study noted a higher kidney cancer risk. Concerns about thyroid cancer risk have also emerged, with a 2025 study from the University of Maryland reporting a “significantly higher” risk within the first year of GLP-1 use, though differentiation between thyroid cancer types was not possible. Other studies, including one in The BMJ, found no clear correlation, emphasizing the need for further research.

The UK Clinical Trial

The University of Manchester, in collaboration with the Manchester Cancer Research Centre and funded by Cancer Research UK, is designing a large-scale clinical trial to rigorously test GLP-1RAs for cancer prevention. Dr. Matthew Harris, a lead researcher, announced plans to enroll tens of thousands of patients within three to five years. The trial aims to determine whether these drugs can be prescribed prophylactically to high-risk individuals, such as those with obesity, before cancer symptoms appear, akin to statins for cardiovascular prevention.

Dr. Harris emphasized the public health implications, noting, “Rates of obesity have been rising substantially across the world for the past 30 years… There’s going to be this massive increase in obesity-related cancers.” With obesity being the second leading cause of cancer in the UK, contributing to over one in 20 cases, the trial seeks to address this growing burden. The study will likely focus on newer, more potent GLP-1RAs like semaglutide and tirzepatide, which offer greater weight loss efficacy than first-generation drugs.

A consensus statement from 54 international experts across 12 countries, including 25 from the UK, issued at the European Congress on Obesity, underscored the urgency of trialing GLP-1RAs for cancer prevention. Experts like Professor Mark Lawler from Queen’s University Belfast described the findings as “transformational,” suggesting that GLP-1RAs could reduce obesity-related cancer risk by nearly 50%, surpassing bariatric surgery’s impact.

Mechanisms Beyond Weight Loss

The anti-cancer effects of GLP-1RAs are believed to stem from multiple mechanisms. Weight loss reduces obesity-driven inflammation, a key contributor to cancer development. However, studies indicate additional benefits, including:

  • Anti-inflammatory Properties: GLP-1RAs reduce systemic inflammation, potentially lowering cancer risk independently of weight loss.
  • Improved Glycemic Control: Better blood sugar regulation may mitigate cancer-promoting metabolic dysfunction.
  • Immune System Enhancement: Small studies suggest GLP-1RAs boost natural killer cell function, which targets cancer cells.
  • Other Metabolic Effects: GLP-1RAs improve liver health, reducing risks of liver cancer and nonalcoholic fatty liver disease.

Professor Dror Dicker from Hasharon Hospital, Israel, noted, “The protective effects of GLP-1RAs against obesity-related cancers likely arise from multiple mechanisms, including reducing inflammation.” These multifaceted benefits position GLP-1RAs as potential “wonder drugs,” though experts caution that long-term safety and efficacy require further study.

Safety and Considerations

While promising, GLP-1RAs are not without risks. Common side effects include gastrointestinal issues like nausea, vomiting, and diarrhea, which are usually manageable. More serious concerns include:

  • Thyroid Cancer Risk: Mixed findings on thyroid cancer necessitate caution, particularly for patients with a family history of medullary thyroid cancer.
  • Pancreatic Safety: A 2024 study in JAMA found no increased pancreatic cancer risk with GLP-1RAs compared to insulin, alleviating earlier concerns about pancreatitis.
  • Mental Health: Some European studies suggested a link to suicidal thoughts, though evidence is inconclusive.
  • Access and Cost: High costs and supply shortages pose barriers to equitable access, potentially complicating trial logistics.

Experts like Dr. Sasan Fazeli from City of Hope Cancer Center recommend that patients consult specialists, particularly those with thyroid cancer risk factors, before starting GLP-1RAs.

Expert Perspectives

The scientific community is cautiously optimistic. Dr. Neil Iyengar from Memorial Sloan Kettering Cancer Center foresees GLP-1RAs revolutionizing obesity-related cancer prevention if access improves. Professor Jason Halford, former president of the European Association for the Study of Obesity, suggested that oncologists might increasingly prescribe these drugs to reduce oncology service burdens. However, researchers like Dr. Megha Poddar from LMC Endocrinology in Toronto stress the need for randomized clinical trials to confirm observational findings, noting that insulin-treated patients in studies were often sicker, potentially skewing comparisons.

Public Sentiment and Media Coverage

Posts on X reflect excitement about the potential of GLP-1RAs, with some claiming up to 50% cancer risk reduction, though others, including @grok, corrected exaggerated claims, citing a 19% reduction for colorectal cancer. Media outlets like The Guardian, The Times, and Business Standard have hailed the findings as a potential “new era” in preventive cancer medicine, emphasizing the trial’s significance.

Future Directions

The Manchester trial will be a critical step in validating GLP-1RAs for cancer prevention. Researchers aim to explore whether these drugs can benefit non-obese individuals with other cancer risk factors, such as genetic predispositions or chronic inflammation. Future studies will also assess newer GLP-1RAs and dual agonists like tirzepatide, which may offer even greater efficacy. Long-term safety, particularly regarding non-obesity-related cancers, remains a priority.

The planned UK trial represents a bold step toward leveraging GLP-1 drugs like Ozempic, Wegovy, and Mounjaro as a preventive strategy against obesity-related cancers. Backed by promising research, these medications could redefine cancer prevention, offering a scalable intervention for a growing public health crisis. However, rigorous clinical trials are essential to confirm efficacy, clarify mechanisms, and ensure safety. As Dr. Harris noted, “Prevention is really important in cancer, especially now we have a weapon to potentially reduce one of the major risk factors, in obesity.” With global obesity rates climbing, the success of this initiative could herald a transformative era in cancer care.