Another large study has found that people who use GLP-1 receptor agonist medications to manage obesity were less likely to be diagnosed with cancer. The risk reduction was particularly notable for endometrial and ovarian cancers and meningioma, a type of brain tumor, according to results published in JAMA Oncology.
“Given that more than 137 million individuals in the U.S. are currently eligible for GLP-1 therapies, even modest changes in cancer risk could have substantial public health implications,” the study authors wrote.
GLP-1 (glucagon-like peptide-1) receptor agonists and related medications mimic natural hormones that suppress appetite, regulate insulin and blood sugar and slow emptying of the stomach; they also appear to have anti-inflammatory effects. Originally developed to treat type 2 diabetes, liraglutide (Victoza), semaglutide (Ozempic) and tirzepatide (Mounjaro) were later approved for obesity treatment (rebranded as Saxenda, Wegovy and Zepbound, respectively).
Medications in this class have been shown to lower the risk of cardiovascular disease and kidney disease and improve fatty liver disease, sleep apnea and arthritis pain. A growing body of evidence indicates that they also protect against cancer. For example, a study published last year found that people with diabetes who used GLP-1 agonists had a significantly lower risk of 10 obesity related malignancies. A study presented at the American Society of Clinical Oncology annual meeting in June found that diabetic people who used the meds had a modestly lower risk of obesity-related malignancies, especially colon and rectal cancer, than those who took another type of diabetes drug.
Now, a new analysis shows that GLP-1 agonists are also associated with lower cancer risk for people using the meds to manage obesity, whether or not they had diabetes.
Hao Dai, PhD, of Indiana University School of Medicine, and colleagues conducted a retrospective cohort study using electronic health records from OneFlorida+, multicenter health research network that collects real-world clinical data from diverse health care settings. Participants were eligible for GLP-1 meds because they either had obesity or were overweight with at least one weight-related comorbidity. The analysis included 43,317 adults with no prior history of cancer who used liraglutide, semaglutide or tirzepatide and 43,315 matched nonusers. Nearly 70% were women, the average age was 52 years and the population was racially diverse. About half had type 2 diabetes.
The researchers looked at 13 types of cancer associated with obesity plus lung cancer. Over 10 years of follow-up, people taking GLP-1 receptor agonists had a significant 17% lower risk of cancer overall. The cancer diagnosis rate was 13.6 cases per 1,000 people per year among those who used the meds compared with 16.4 cases among nonusers.
Looking at specific malignancies, most showed a trend toward modestly lower risk. Of note, this was the case for thyroid cancer, which was linked to GLP-1 agonists in some early research, though recent larger studies have not seen this association.
The risk reduction was greatest for ovarian cancer (47%), endometrial cancer (25%) and meningioma (31%), all of which were statistically significant. However, GLP-1 medication users had an 38% increased risk for kidney cancer, which did not reach the threshold for statistical significance. This was most notable among those under age 65 and those who were overweight rather than obese.
“These findings suggest taking GLP-1 receptor agonists may influence cancer risk, highlighting the need for long-term follow-up to understand underlying mechanisms,” the study authors concluded.
The patterns seen in this study raise the hypothesis that GLP-1 receptor agonists “may be associated with a lower risk of hormone-sensitive malignant neoplasms,” they suggested in their discussion. Preclinical studies, they noted, have shown that drugs in this class inhibit the growth of endometrial and ovarian cancer cells in the lab. Regarding meningioma, an analysis found that about a third of meningioma tumors express GLP-1 receptors, so receptor agonist drugs may have a more direct effect.
As a limitation of the study, the database did not include body mass index measurements over time, so “the study could not disentangle whether the observed cancer risk reduction was due to GLP-1 receptor agonists themselves or drug-induced weight loss,” the authors acknowledged.
“Given the relatively recent approval and widespread uptake of GLP-1 receptor agonists, the study’s follow-up duration may not have been sufficient to fully capture their long-term effects on cancer risk,” they wrote. “This limitation, rooted in the underlying biology of cancer development, highlights the need for extended longitudinal follow-up in future research.”
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