GLP-1s tied to lower risk for 10 types of cancer compared with insulin in type 2 diabetes
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Key takeaways:
- People with type 2 diabetes using a GLP-1 medication have a lower risk for most obesity-associated cancers than insulin users.
- The risk for most types of cancer was similar between GLP-1 and metformin users.
People with type 2 diabetes who use a GLP-1 receptor agonist have a lower risk for 10 types of obesity-associated cancer compared with those who use insulin, according to data published in JAMA Network Open.
“This study adds to the growing body of evidence supporting the pleiotropic effects of GLP-1 receptor agonists on cancer prevention,” Lindsey Wang, an undergraduate student in the pre-professional scholars program at Case Western Reserve University, told Healio. “For patients with type 2 diabetes, particularly those with obesity, GLP-1 receptor agonists may offer protective benefits against specific cancers. Clinicians might consider preferring GLP-1 receptor agonists over other diabetes treatments, such as insulin, for patients at high risk of obesity-associated cancers.”
Wang and colleagues conducted a retrospective cohort study of deidentified electronic health records on the TriNetX platform. People with type 2 diabetes who were prescribed a GLP-1 receptor agonist, insulin or metformin and had no history of an obesity-associated cancer from March 2005 to November 2018 were included (mean age, 59.8 years; 50.1% men). Researchers collected diagnoses of 13 types of obesity-associated cancer. Two analyses were conducted using propensity-score matching for baseline covariates. People using a GLP-1 and no insulin were matched, 1:1, with those using insulin and no GLP-1 in the first analysis. The second analysis matched people using a GLP-1 and no metformin, 1:1, with those using metformin and no GLP-1.
Compared with those using insulin, people using a GLP-1 receptor agonist had a lower risk for developing gallbladder cancer (HR = 0.35; 95% CI, 0.15-0.83), meningioma (HR = 0.37; 95% CI, 0.18-0.74), pancreatic cancer (HR = 0.41; 95% CI, 0.33-0.5), hepatocellular carcinoma (HR = 0.47; 95% CI, 0.36-0.61), ovarian cancer (HR = 0.52; 95% CI, 0.03-0.74), colorectal cancer (HR = 0.54; 95% CI, 0.46-0.64), multiple myeloma (HR = 0.59; 95% CI, 0.44-0.77), esophageal cancer (HR = 0.6; 95% CI, 0.42-0.86), endometrial cancer (HR = 0.74; 95% CI, 0.6-0.91) and kidney cancer (HR = 0.76; 95% CI, 0.64-0.91). No difference in stomach cancer, postmenopausal breast cancer or thyroid cancer risk was seen between the two groups.
“One particularly noteworthy association that stood out is the significant risk reduction across multiple gastrointestinal cancers, including colorectal, esophageal, stomach, gallbladder, liver and pancreatic cancers,” Wang said. “This is especially important given the often poor prognosis of these cancers. Surprisingly, no associations were found between GLP-1 receptor agonists and breast cancer risk.”
People prescribed GLP-1s had a higher risk for kidney cancer compared with those receiving metformin (HR = 1.54; 95% CI, 1.27-1.87). No difference in risk between the two groups was observed for any other obesity-associated cancer.
Wang said several types of studies are needed to further explore the link between GLP-1s and obesity-associated cancers.
“Prospective randomized clinical trials are essential to confirm these associations and establish causality,” Wang said. “Preclinical studies are needed to elucidate the underlying mechanisms. Additionally, research to examine the newer and more potent weight-loss GLP-1 receptor agonists, semaglutide (Ozempic/Wegovy, Novo Nordisk) and tirzepatide (Mounjaro/Zepbound, Eli Lilly), would be particularly important.”
Perspective
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With the rapid increase in use of GLP-1 receptor agonists, the question of the impact of this class of medications on cancer risk frequently arises. Pre-clinical studies found increased risks for certain cancers. On the other hand, as obesity is a known risk factor for certain cancers, given the profound weight loss that occurs with semaglutide and tirzepatide, it is often hypothesized that these medications could reduce cancer risk.
In this study, the authors reported that individuals with type 2 diabetes treated with GLP-1 receptor agonists had a significantly lower risk for developing a number of obesity-associated cancers, compared with individuals taking insulin between 2005 and 2018, before the era of semaglutide and tirzepatide. As the authors state, it is a retrospective, observational study and in no way should the results be interpreted as causal.
The associations should also be interpreted with caution. While the authors performed propensity score matching, they matched for cancer risk factors, but not for diabetes-related factors that are known to impact cancer risk, such as years of diabetes and diabetes control. Looking at the data on colorectal cancer in the study as one example, it is surprising that the cancer incidence between the GLP-1 receptor agonist and insulin groups separated immediately in the follow-up period. Colorectal cancer has well-described premalignant stages, so it is difficult to explain how the incidence could separate so quickly if exposure to insulin or GLP-1 receptor agonist were the factors affecting the cancer incidence.
Overall, this is an interesting and topical study, but we should be careful not to overinterpret the results.
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