Only last week, we reported on one of the few negative stories about semaglutide, a member of the class of drugs known as glucagon-like peptide 1 receptor agonists (GLP-1s or GLP-1RAs) that are used to treat diabetes and/or weight loss.
It appears that the negative news cycle was short-lived. A new study led by the Case Western Reserve University (CWRU) School of Medicine has added yet another effect to the growing list of positive things that GLP-1RAs can do: reduce the risk of obesity-associated cancers.
Thirteen types of cancer have been identified as obesity-associated cancers (OAC): gallbladder, meningioma, pancreatic, liver (hepatocellular carcinoma), ovarian, colorectal, multiple myeloma, esophageal, endometrial, stomach, breast, thyroid, and kidney. Obesity and type 2 diabetes also go hand-in-hand, and patients are prescribed GLP-1RA medications to treat either or both conditions. Commonly prescribed GLP-1RAs include semaglutide (Ozempic, Wegovy), liraglutide (Saxenda, Victoza) and dulaglutide (Trulicity).
The researchers examined the deidentified electronic health records of more than 1.6 million US patients diagnosed with type 2 diabetes and prescribed GLP-1RAs or another diabetes medication (insulin or metformin) who had medical encounters with healthcare organizations between March 2005 and November 2018. None had a history of any of the 13 OACs. Study participants were 47% female and included people identifying as American Indian or Alaskan Native, Asian, Black, Native Hawaiian or other Pacific Islander. The study population was divided according to each participant’s prescribed medication for comparison (e.g., prescribed GLP-1RAs but not prescribed insulin vs insulin prescribed but not GLP-1RAs).
Compared with insulin, GLP-1RAs were associated with a significantly lower risk for 10 of the 13 OACs: gallbladder cancer risk was reduced by 65%, meningioma by 63%, pancreatic cancer by 59%, hepatocellular carcinoma by 53%, ovarian cancer by 48%, colorectal cancer by 46%, multiple myeloma by 41%, esophageal cancer by 40%, endometrial cancer by 26%, and kidney cancer by 24%. There was no association between GLP-1RAs and postmenopausal breast cancer or thyroid cancer. There was a reduction in risk in relation to stomach cancer (27%), but it was not statistically significant.
Compared with metformin, GLP-1RAs were associated with a decreased risk of colorectal cancer, gallbladder cancer and meningiomas, but it was not statistically significant. However, the researchers found an increased risk of kidney cancer in the GLP-1RA group compared with metformin.
“In this study of patients with T2D [type 2 diabetes] who were cancer-free at baseline, taking GLP-1RAs compared with insulin was associated with a lower risk of 10 of 13 OACs,” said the researchers. “The potential cancer-preventative effects of OACs by GLP-1RAs warrant further long-term studies as well as studies of individual newer and possibly more effective antidiabetic and weight loss agents … Studies are also warranted to evaluate the preventive effects of these agents on non-OACs.”
The researchers don’t offer a mechanism by which GLP-1RAs exert their cancer-inhibiting effects but say that their findings regarding kidney and breast cancer require further study. To their knowledge, there have been no prior reports of kidney cancers with the use of GLP-1RAs, but they urge continued monitoring of patients taking this class of drugs. The lack of effect of GLP-1RAs on breast cancer needs to be investigated to determine the impact of longer-term treatment and to better understand the relationship between GLP-1RAs and estrogen metabolism.
The researchers note the study’s limitations. As a retrospective observational study of patient health records, it has inherent limitations, including over-, under-, and misdiagnosis and biases. Although an extensive list of variables was controlled for, these limitations and biases couldn’t be eliminated fully. Also, because of the lack of information regarding patients’ adherence to medication, the researchers used an ‘intention-to-treat’ (that is, medication prescriptions) for comparison, whether or not individuals adhered to their prescribed medication regime.
The study was published in the journal JAMA Network.
Source: CWRU School of Medicine via Scimex
