Porto Alegre, Brazil—For years, reports of higher risks of breast and bladder cancer with the use of SGLT2i have raised concerns.

A recent study in Diabetes Research and Clinical Practice pointed out that the issue has remained controversial and the drug classes’ effect on cancer mortality continued to be unknown.

In response, a Brazilian study with involvement from U.S. researchers sought to evaluate the association between SGLT2i and the risk of cancer outcomes.

To do that, the study team searched PubMed, Embase, and CENTRAL up to June 20, 2022, for randomized, controlled trials of SGLT2i in adults with a minimum follow-up of 48 weeks. It performed meta-analyses summarizing the relative risks (RRs) of cancer outcomes.

Included were 76 trials encompassing 116,375 participants, with the researchers advising that the overall risk of bias was low.

The results indicated that SGLT2i did not reduce/increase the overall risk of cancer (RR 1.03; 95% CI, 0.96-1.10) and cancer mortality (RR 0.99; 95% CI, 0.85-1.16). “SGLT2 inhibitors likely result in little to no difference in the risk of breast (RR 1.01; 95% CI, 0.77-1.32) and bladder cancers (RR 0.93; 95% CI, 0.71-1.21). The trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results,” the authors explained.

The study concluded that SGLT2i are not associated with an increased risk of cancer outcomes, providing reassuring data regarding previous safety concerns.

Further bolstering the information was a Taiwanese study in the Journal of Diabetes Complications. The study looked at patients with diabetes with and without SGLT2i use, comparing with cancer incidence.

“The burden of diabetes mellitus is growing dramatically, mainly through its atherosclerotic cardiovascular impact. On the contrast, diabetes is also associated with cancer development and the mechanism underlying this phenomenon is complicated,” the authors wrote.

The researchers added that “to identify the role of pharmacologic intervention in incident cancer among diabetic individuals is truly novel and interesting and clearly of importance for health care delivery and quality control efforts. Therefore, this study was conducted for evaluation of the relation between SGLT2 inhibitors and risk of incident cancer among patients with diabetes with large size of the database examined, and the clinical importance of the question examined.”

The researchers identified a non-SGLT2i cohort of 325,989 patients and an SGLT2i cohort of 325,990 patients. They found that patients receiving SGLT2i (adjusted hazard ratio 0.79, 95% CI, 0.76-0.83) had a significantly lower risk of developing cancer than patients without receiving SGLT2i.

“The results demonstrated that patients with diabetes receiving SGLT2 inhibitors had a significantly lower risk of cancer,” the authors reported.

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