Weight loss medications show promise in preventing obesity-related cancers

A study of more than 229,000 obese adults without diabetes in the United States has shown that weight loss drugs are associated with a decreased risk of obesity-related cancers.

The research found that GLP-1 receptor agonists (GLP-1 RAs), such as semaglutide (brand names: Ozempic, Wegovy) and tirzepatide (brand names: Mounjaro and Zepbound), were associated with a 41% decrease in the overall risk of developing cancer among non-diabetic patients who used the drugs for weight management, compared to those who relied on diet and exercise alone.

Published today (Monday) in the leading cancer journal Annals of Oncology, the study is the first to investigate the link between GLP-1 RAs and the incidence of obesity-related cancers in people who are obese (body mass index of 30 or more) but who do not have diabetes. These patients tend to be younger than those who do have diabetes.

Thirteen cancers have been linked to obesity, known as obesity-associated cancers; they include endometrial, breast, bowel, kidney, pancreatic, thyroid, ovarian, oesophageal, gastric, liver and gallbladder cancers, and multiple myeloma and meningioma. They account for about 40% of cancers diagnosed in high-income countries, and their incidence is rising rapidly among younger adults.

Senior author of the study, Dr Aparna Kamat, director of the Division of Gynecologic Oncology at Houston Methodist Hospital, Houston, Texas, USA, said: "Our study found that over an average follow-up of two years, GLP-1 RA use was associated with a significantly lower incidence of cancers directly fuelled by excess body weight. Overall cancer risk was reduced by 41% and we saw even larger reductions in certain subgroups, including men, where the risk dropped by nearly 70%. Among gynaecologic cancers, there was a 58% reduction in the incidence of endometrial cancer, one of the malignancies most closely linked to obesity.

"The reduction in obesity-related cancer risk among white patients was about 50% but this risk reduction was not observed among black patients. This may reflect additional causes such as access to care, differing risk profiles and other biological differences.

"We also studied the different GLP-1 RA formulations and found that while all of them reduced the incidence of obesity-related cancers, the greatest reduction was seen among tirzepatide users."

GLP-1 RAs were developed initially to treat diabetes but have rapidly become the most widely used medications for weight loss. In the US, GLP-1 RAs use among obese, non-diabetic adults has increased from approximately 21,000 patients in 2019 to more than 174,000 in 2023.

Dr Kamat said: "We already had evidence suggesting these drugs might reduce cancer risk in diabetic patients, but most of the people now taking GLP-1 RAs for weight loss do not have diabetes. They are younger obese patients and represent a completely different population. We wanted to investigate whether these medications would affect the risk of obesity-associated cancers in this specific population of patients who make up the majority of GLP-1 RA users in the country – no one had studied this before.

"GLP-1 RAs are already transforming how we treat obesity. What this analysis of more than 229,000 patients tells us is that their impact may reach further and transform how we think about cancer prevention."

The researchers analysed records from 229,467 obese, non-diabetic patients drawn from a nationwide database (TriNetX) covering 113 million US patients. Between December 2014 and June 2025, 86,422 patients (38%) received prescriptions for GLP-1 RAs (semaglutide or tirzepatide) and 143,045 (62%) received advice on diet and exercise. They were followed up until a cancer was diagnosed, or they died or were lost to follow-up, or for two years following their first prescription of the drugs or diet and exercise counselling. The average age of the patients was 47 years.

After closely matching the GLP-1 RA patients with the diet and exercise patients to ensure a fair comparison between the two groups and to emulate the conditions of a randomised controlled trial, there was a total of 161,796 patients, with 80,899 patients in each group.

The second author of the study, Professor Pedro Ramirez, who is chair of the Department of Obstetrics and Gynecology at Houston Methodist Hospital, said: "Our study suggests GLP-1 RAs may have benefits that extend beyond weight management. It should be noted that while the findings do not prove that GLP-1 drugs directly prevent cancer, they provide early evidence that deserves further study in long-term clinical trials."

Dr Kamat said: "Given the significant reduction in endometrial cancer incidence among GLP-1 RA users in the study, we are now looking into mechanisms by which GLP-1 RAs may affect endometrial cancer growth and prognosis. We are studying mechanistic pathways that are modulated by these drugs – work that could open new treatment strategies for one of the most common gynaecologic malignancies."

The researchers say that their findings require further research, especially as the duration of follow-up was only two years. In the meantime, doctors and patients should consider the potential benefit of cancer prevention when discussing GLP-1 RA use.

"Our findings do not prove causation, and cancer risk reduction should not yet be a stand-alone reason to prescribe GLP-1 RAs. However, for obese, non-diabetic patients who are already candidates for these medications, our data provide an additional and potentially important reason to have that conversation," said Dr Kamat.

"For policymakers and other researchers, our study is a clear signal that GLP-1 RAs deserve serious investigation as cancer prevention agents, particularly as obesity-related cancers increasingly affect adults in their 40s and 50s."

Pedro Ramirez, Professor, Department of Obstetrics and Gynecology, Houston Methodist HospitalThis study highlights the potential for a major shift in how we think about obesity treatment and cancer prevention. As the use of GLP-1 RA medications continues to grow worldwide, understanding their broader health impact is critically important. At Houston Methodist Hospital, we are committed to leading innovative, data-driven research that has the potential to improve patient outcomes far beyond traditional boundaries of care."

Source:

European Society for Medical Oncology

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