In adults with diabetes, the risk of developing a wide range of cancers appears to be lower among those treated with sodium glucose cotransporter-2 (SGLT2) inhibitors than among those not receiving the medications, report investigators from Taiwan.
The findings, based on data from nearly 326 000 adults taking SGLT-2 inhibitors and a group of the same size matched for age and sex not taking the agents, also suggest that risk for cancers may decrease in a linear fashion with duration of SGLT2 inhibitor use.
The exception to the results was an increased risk for pancreatic cancer among SGLT2 inhibitor-treated participants with diabetes vs those not treated, according to the study.
Writing in the Journal of Diabetes and its Complications, Wei-Syun Hu, MD, PhD, assistant professor of medicine at China Medical University and attending physician of cardiovascular medicine at China Medical University Hospital in Taiwan, and colleagues, cited the “pluripotent” effects that have accrued to the class of SGLT2 inhibitors over years of clinical research and noted that exploring a potential role for the drugs as a “pharmacologic intervention in incident cancer” among individuals with diabetes would be “novel and interesting and clearly of importance for health care delivery and quality control efforts.”
Tapping the National Health Insurance database in Taiwan, Hu and colleagues collected background on 325 990 adults with diabetes being treated with an SGLT2 inhibitor between 2016 and 2019. This cohort (57.8% men; mean age 58.8 years) was age- and sex-matched with a second group of adults with diabetes who were not treated with an agent in the class. Baseline data were collected on comorbidities as well as other medications used.
The primary outcome of interest was the difference in risk of incident cancer between those treated and not treated with SGLT2 inhibitors with secondary outcomes including the association between SGLT2 inhibitor use and specific types of cancer.
Overall, the investigators found that the risk of developing any cancer was lower among adults with diabetes who received SGLT2 inhibitors than among those who did not (adjusted HR [aHR], 0.79; 95% CI, 0.76-0.83). Among specific subgroups, Hu et al report that the risk for incident cancer was higher among men vs women (aHR, 1.35; 95% CI, 1.3-1.41) and higher among adults aged ≤49 years than among those aged 50 to 64 years (aHR, 2.47; 95% CI, 2.3-2.66) and those aged ≥65 years (aHR, 4.31; 95% CI, 3.99-4.65).
When they analyzed the risk of specific cancer types between those who used and did not use SGLT2 inhibitors the researchers found SGLT2 inhibitor use was associated with reduced risk for cancer of the:
The investigators did observe, however, a greater risk for pancreatic cancer among those with diabetes treated with SGLT2 inhibitors than those who were not (aHR, 1.51; 95% CI, 1.22-1.87), a finding the authors considered might be “reasonable,” given the elevated risk of pancreatitis seen in some clinical trials with the class and noted on class labeling.
Of further interest to the research team was the differential impact of duration of SGLT2 inhibitor treatment on incident cancer. Their analysis found that adults who used SGLT2 inhibitors for fewer than 60 days or for 60 to 140 days were more likely to develop cancer than those who did not use the drugs. The risk was lower, however, in adults who had taken an agent in the class for 140 to 280 days (aHR, 0.73; 95% CI, 0.68-0.78) and for >280 days (aHR = 0.26; 95% CI, 0.23-0.28).
In conclusion the authors note that while the findings are suggestive of an important mitigating effect of SGLT2 inhibitor use on cancer risk in persons with diabetes, particularly when treatment is sustained, the observational nature of the study makes it difficult to address “the detailed mechanism underlying the observation.
“Nonetheless,” they add, “the trend is clear and based upon a well validated nationwide dataset. Further prospective mechanism exploring research is necessary.”
Reference: Hu W-S, Lin C-L. Patients with diabetes with and without sodium-glucose cotransporter-2 inhibitors use with incident cancer risk. J Diabetes Complications. 2023;37. doi:10.1016/j.jdiacomp.2023.108468