, 2025-05-07 07:53:00
SAN DIEGO — Patients with obesity and type 2 diabetes treated with glucagon-like peptide 1 (GLP-1) receptor agonists had significantly reduced rates for colorectal cancer (CRC) risk and associated mortality compared with those undergoing bariatric surgery, new research showed.
CRC risk was also lower for patients taking GLP-1s than the general population.
“Our findings show we might need to evaluate these therapies beyond their glycemic or weight loss [effects],” said first author Omar Al Ta’ani, MD, of the Allegheny Health Network, Pittsburgh.
This supports future prospective studies examining GLP-1s for CRC reduction, added Ta’ani, who presented the results at Digestive Disease Week (DDW) 2025.
Patients with type 2 diabetes and obesity are known to have a higher risk for CRC, stemming from metabolic risk factors. While prior studies suggested that GLP-1s decrease the risk for CRC compared with other antidiabetic medications, studies looking at the risk for CRC associated with bariatric surgery have had more mixed results, Ta’ani said.
For the comparison, Ta’ani and colleagues conducted a retrospective analysis of the TriNetX database, identifying patients with type 2 diabetes and obesity (a body mass index [BMI] over 30), enrolled in the database between 2005 and 2019.
Overall, the study included 94,098 GLP-1 users and 24,969 patients who underwent bariatric surgery. Those with a prior history of CRC were excluded.
Using propensity score matching, patients treated with GLP-1s were matched 1:1 with patients who had bariatric surgery based on wide-ranging factors including age, race, gender, demographics, diseases, medications, personal and family history, and A1c.
After the propensity matching, each group included 21,022 patients. About 64% in each group were women; their median age was 53 years and about 65% were White individuals.
Overall, the results showed that patients on GLP-1s had a significantly lower CRC risk compared with those who had bariatric surgery (adjusted hazard ratio [aHR], 0.29; P < .0001). The lower risk was also observed among those with high obesity (defined as BMI over 35) compared with those who had surgery (aHR, 0.39; P < .0001).
The results were consistent across genders, however, the differences between GLP-1s and bariatric surgery were not observed in the 18- to 45-year-old age group (P = .0809, BMI > 30; P = .2318, BMI > 35).
When compared with the general population, patients on GLP-1s also had a reduced risk for CRC (aHR, 0.28; P < .0001), however, the difference was not observed between the bariatric surgery group and the general population (aHR, 1.11; P = .3).
Among patients with type 2 diabetes with CRC and a BMI over 30, the 5-year mortality rate was lower in the GLP-1 group vs the bariatric surgery group (aHR, 0.42, P < .001).
Speculating on the mechanisms of GLP-1s that could result in a greater reduction in CRC risk, Ta’ani explained that the key pathways linking type 2 diabetes, obesity, and CRC include hyperinsulinemia, chronic inflammation, and impaired immune surveillance.
Studies have shown that GLP-1s may be more effective in addressing the collective pathways, he said. They “may improve insulin resistance and lower systemic inflammation.”
Furthermore, GLP1s “inhibit tumor pathways like Wnt/beta-catenin and PI3K/Akt/mTOR signaling, which promote apoptosis and reduce tumor cell proliferation,” he added.
Bariatric Surgery Findings Questioned
Meanwhile, “bariatric surgery’s impact on CRC remains mixed,” said Ta’ani.
Commenting on the study, Vance L. Albaugh, MD, an assistant professor of metabolic surgery at the Metamor Institute, Pennington Biomedical Research Center, Baton Rouge, Louisiana, noted that prior studies, including a recent meta-analysis, suggest a potential benefit of bariatric surgery in cancer prevention.
“I think the [current study] is interesting, but it’s been pretty [well-reported] that bariatric surgery does decrease cancer incidence, so I find it questionable that this study shows the opposite of what’s in the literature,” Albaugh, an obesity medicine specialist and bariatric surgeon, told Medscape Medical News.
Ta’ani acknowledged the study’s important limitations, including that with a retrospective design, causality cannot be firmly established.
And, as noted by an audience member in the session’s Q and A, the study ended in 2019, which was before GLP-1s had taken off as anti-obesity drugs and before US Food and Drug Administration approvals for weight loss.
Participants were matched based on BMI, however, Ta’ani pointed out.
Albaugh agreed that the study ending in 2019 was a notable limitation, however, the relatively long study period — extending from 2005 to 2019 — was a strength.
“It’s nice to have a very long period to capture people who are diagnosed, because it takes a long time to develop CRC,” he said. “To evaluate effects [of more recent drug regimens], you would not be able to have the follow-up they had.”
Other study limitations included the need to adjust for ranges of obesity severity, said Albaugh. “The risk of colorectal cancer is probably much different for someone with a BMI of 60 vs a BMI of 30.”
Ultimately, a key question the study results raise is whether GLP-1 drugs have protective effects above and beyond that of weight loss, he said.
“I think that’s a very exciting question and that’s what I think the researchers’ next work should really focus on.”
Ta’ani had no disclosures to report. Albaugh reported that he had consulted for Novo Nordisk.
