Patients with a history of GLP-1 receptor agonist treatment had a significantly lower risk of developing colorectal cancer (CRC) as compared with those who took aspirin, according to a retrospective study reported here.
A history of GLP-1 receptor agonist treatment was associated with a 36% reduction in the odds of developing CRC versus aspirin, and this increased to 42% among high-risk individuals. A clear trend in favor of GLP-1 agonists persisted across all prespecified subgroups, including by age, body mass index (BMI), atherosclerosis and diabetes status, and different types of GLP-1 agonists.
Furthermore, GLP-1 drugs had a favorable safety profile versus aspirin, particularly with respect to bleeding events, said Colton Frisco Jones, MD, of the University of Texas at San Antonio, during a press briefing prior to the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.
"The large population size [more than 280,000 patients] of this study and the favorable safety profile of GLP-1 receptor agonists versus aspirin could underscore a potential public health impact," said Jones. "These findings warrant prospective validation in randomized clinical trials."
The study is thought provoking, given the longstanding interest in aspirin and nonsteroidal anti-inflammatory drugs for CRC prevention and the recognition of aspirin's side effects, creating a challenge for use in a broad patient population, said ASCO discussant Joel Saltzman, MD, of the Cleveland Clinic.
"It will certainly be interesting over the upcoming years to see how these drugs fit in [CRC prevention] and what we can learn from the development of cancer and how it really ties into obesity as perhaps a cause of cancer," said Saltzman.
During a discussion that followed, Jones hinted at the possibility of additional data suggesting that the potential cancer-reducing benefits of GLP-1 agonists may extend across multiple types of cancer. Noting that he has submitted abstracts for presentation at the ASCO annual meeting later this year, Jones said he did not want to reveal too much about the research at this point.
"It could be widespread," Jones said of GLP-1 agonists' impact on cancer prevention.
Jones also responded to a recent meta-analysis of randomized trials of GLP-1 agonists, which showed "little or no effect" of the drugs on the risk of obesity-related cancers.
"Most of those randomized controlled trials were not actually designed to evaluate cancer as a primary outcome," he said. "That's one of the limitations of the meta-analysis. In addition, most of the studies had relatively short follow-up, only 1 or 2 years. I don't think that is long enough to detect long-latency effects, including both cancer prevention and cancer risk."
Aspirin for CRC prevention has been investigated extensively, but modest efficacy and bleeding risks have limited widespread use. Interest in GLP-1 agonists' CRC prevention potential has increased with evidence that the drugs regulate the PI3K/AKT/mTOR signaling pathway, but the issue has remained largely unexplored, said Jones.
To compare CRC prevention with GLP-1 agonists or aspirin, the investigators queried the TriNetX database, which encompasses 150 million patients in 106 health organizations. They identified 149,115 patients with a history of exposure to GLP-1 agonists and 3,011,724 with a history of aspirin use. After propensity matching, the analysis involved two groups with 140,828 patients each. The primary endpoint was CRC incidence.
The study population had a median age of 58, two-thirds of patients were white, and two-thirds were women. Median follow-up was about 6 years in the GLP-1 group and 5 years for the aspirin users.
The results showed that GLP-1 agonist use was associated with a CRC hazard of 0.643 versus the aspirin group (95% CI 0.531-0.778). Among high-risk patients -- those with mutations associated with CRC, family history, or high-risk comorbidities -- the hazard ratio decreased to 0.579 in the GLP-1 agonist group.
Subgroup analysis consistently favored GLP-1 agonists, including for all age groups (lowest hazard in the youngest patients, 0.583), normal or high BMI, history of atherosclerosis, and history of diabetes (lower hazard in non-diabetic patients, 0.588). Across four types of GLP-1 agonists, the CRC hazard ranged from 0.436 with liraglutide (Victoza, Saxenda) to 0.711 with tirzepatide (Mounjaro, Zepbound) and achieved statistical significance for all except tirzepatide.
GLP-1 agonists were associated with fewer episodes of gastrointestinal bleeding (2.0% vs 2.1%, HR 0.852, P=0.018), gastric ulcers (0.5% vs 0.55%, HR 0.815, P=0.038), and acute kidney injury (1.15% vs 2.8%, HR 0.369). Patients treated with GLP-1 agonists had higher rates of diarrhea (6.8% vs 5.4%, HR 1.131, P=0.0001) and abdominal pain (19.0% vs 16.3%, HR 1.055, P=0.0001). Rates of nausea and vomiting were similar with GLP-1 agonists (10.5%) and aspirin (9.7%, HR 0.98).
Disclosures
Jones reported no relevant financial disclosures.
Saltzman has disclosed relationships with Pfizer and Seagen.
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