Could a diabetes drug slash your cancer risk? New research shows GLP-1 receptor agonists may protect patients with type 2 diabetes from deadly blood cancers—beyond just managing blood sugar.
Glucagon-like peptide 1 (GLP-1, 7-36) molecule — a potent antihyperglycemic hormone, neuropeptide, and incretin. Research letter: Hematologic Cancers Among Patients With Type 2 Diabetes Prescribed GLP-1 Receptor Agonists. Image Credit: ALIOUI MA / Shutterstock
In a recent study published in the journal JAMA Network Open, researchers compared the risk of hematologic cancers in type 2 diabetes (T2D) patients treated with glucagon-like peptide 1 receptor agonists (GLP-1RAs).
Obesity and T2D have been recognized as independent risk factors for multiple cancers, including hematologic cancers. GLP-1RAs have emerged as a promising treatment, offering weight reduction, immune modulation, and glycemic control. Moreover, GLP-1RAs are associated with a lower risk of cancer, especially solid tumors. Nevertheless, the association between GLP-1RAs and hematologic cancers remains unexplored.
About the study
In the present study, researchers examined the risk of hematologic cancers in T2D patients receiving GLP-1RAs compared to those receiving insulin or metformin. The team identified T2D patients prescribed insulin, metformin, or GLP-1RAs from April 30, 2005, to October 31, 2023, using TriNetX, a repository of health records of approximately one-fourth of the United States population.
Individuals with hematologic cancers and those prescribed antidiabetic medicines before T2D diagnosis were excluded. Recipients of GLP-1RAs (exenatide, lixisenatide, tirzepatide, liraglutide, albiglutide, semaglutide, or dulaglutide) constituted the experimental group. The primary outcome of the study was the first hematologic cancer diagnosis. One analysis compared GLP-1RA recipients to metformin recipients, and another compared the former to those taking insulin.
Study groups were propensity-matched for weight status, demographics, diabetic complications, body mass index (BMI), glycated hemoglobin (HbA1c), cancer screenings, genetic susceptibility, radiation, intensive care unit (ICU) admissions, antidiabetic agents, adverse social determinants, and cytotoxic agents. Kaplan-Meier survival and Cox proportional hazard analyses were performed to estimate cumulative incidences and hazard ratios with 95% confidence intervals.
Findings
In total, the researchers identified more than 1.6 million T2D patients. Of these, 51,617 received GLP-1RAs, 938,602 received insulin, and 611,115 received metformin. The average prescription duration of GLP-1RAs was 485 days. After propensity matching, 50,590 and 47,716 patients were included in the GLP-1RA–metformin and GLP-1RA–insulin analyses, respectively.
The researchers found that the use of GLP-1RAs was associated with a significantly reduced risk of myelodysplastic syndromes (MDSs) and myeloproliferative neoplasms (MPNs) compared to metformin use. The researchers noted that metformin itself may have cancer-protective properties, which could explain why GLP-1RAs showed limited additional benefit against other cancers in this comparison. Nonetheless, there were no significant differences in the overall risk of other hematologic cancers. Importantly, the combined risk of all hematologic cancers was not significantly different between GLP-1RA and metformin users.
Further, compared to insulin use, GLP-1RA use was associated with a significantly reduced risk of lymphoid leukemia, myeloid leukemia, MPN, MDS, amyloidosis, non-Hodgkin lymphoma, monoclonal gammopathy, and multiple myeloma. Across all hematologic cancers, GLP-1RA use was associated with a 54% lower risk compared to insulin.
Conclusions
The findings illustrate that GLP-1RAs are associated with a lower risk of various hematologic cancers, especially MDS and MPN, in T2D patients. These protective effects were more pronounced when GLP-1RAs were compared to insulin than to metformin, likely due to metformin’s own potential cancer-protective effects. The immunomodulatory features of GLP-1RAs and weight loss may mediate this decline in risk. Moreover, these associations were independent of glycemic control, potentially through the decrease in pro-inflammatory cytokines implicated in the dysregulation of hematopoiesis and the development of MPN and MDS.
The study’s limitations include residual confounding, unexplored dose-response relationships, lack of age stratification, and limited adjustment for multiple testing. Because this was a retrospective analysis relying on diagnostic codes and electronic health records, potential inaccuracies in coding and unmeasured confounding cannot be ruled out. When interpreting results, the authors emphasized that metformin, the comparator, may itself reduce cancer risk, which could partly explain the narrower benefits seen in that arm. Overall, GLP-1RAs could be a promising strategy to reduce the risk of cancer. However, additional studies are required to investigate the pathways of GLP-1RAs implicated in cancer prevention and to confirm these observational findings.