Electronic Thesis and Dissertation Repository

Thesis Format



Master of Science


Epidemiology and Biostatistics


Garg, Amit X.


Regulatory agencies warn about acute kidney injury (AKI) risk following sodium-glucose cotransporter-2 (SGLT2) inhibitor use. This population-based retrospective cohort study in Ontario, Canada quantified the 90-day AKI risk in older adults who were newly dispensed either SGLT2 inhibitors or dipeptidyl peptidase-4 (DPP4) inhibitors in an outpatient setting between 2015 and 2017. Risk ratios (RR) were obtained using modified Poisson regression and risk differences using binomial regression. Relative to new use of a DPP4 inhibitor, initiation of an SGLT2 inhibitor was associated with a lower 90-day risk of a hospital encounter with AKI: 216 events in 19,611 patients (1.10%) versus 388 events in 19,483 patients (1.99%); weighted RR 0.79 (95% confidence interval 0.64–0.98). In routine care of older adults, new SGLT2 inhibitor use was associated with lower risk of AKI. Together with previous evidence, these findings suggest that regulatory warnings about AKI risk with SGLT2 inhibitors may be unwarranted.

Summary for Lay Audience

The number of drugs used to treat patients with diabetes has grown significantly. Sodium-glucose costransporter-2 (SGLT2) inhibitors are an example of a new class of diabetes medications that help lower blood sugar by promoting its loss in the urine. Despite the ability of SGLT2 inhibitors to lower blood sugar, the US Food and Drug Administration (FDA) and Health Canada have issued safety warnings of the link between SGLT2 inhibitors and kidney injury. These warnings were made based on individual case reports and case series. We used health administrative databases to examine elderly patients with diabetes who were prescribed SGLT2 inhibitors and we examined kidney injury. We found that, in the first 90 days after being prescribed an SGLT2 inhibitor, patients had lower risk of developing kidney injury, compared to a similar group of people taking different diabetes medications. We suggest that the safety warnings and concerns about SGLT2 inhibitors and the risk of kidney injury might be revisited.