Background: Expansion of sodium-glucose cotransporter-2 inhibitor (SGLT2i) use in chronic kidney disease (CKD) prompted a pragmatic study of their safety and effectiveness in patients with type 2 diabetes mellitus (T2DM) and late-stage CKD. Objective: The primary clinical endpoint was change in HbA1c. Secondary clinical endpoints included change in body weight and blood pressure. Safety endpoints included kidney function indices, mycotic or urinary tract infection, acute kidney injury, dehydration, and ketoacidosis. Methods: Adult patients with T2DM and late-stage CKD prescribed an SGLT2i between June 1, 2018 and June 1, 2023 were included in this retrospective cohort study. Late-stage CKD was defined as CKD stage G3b, G4, or G5, including requiring dialysis or kidney transplantation. Endpoints were compared between patients who continued an SGLT2i versus those who discontinued. Results: Fifty-nine patients were included. Short-term follow-up over 4.2 ± 1.7 months revealed no difference in HbA1c between groups. Extended follow-up in a truncated sample over 10.4 ± 2.6 months showed modest, yet significantly lower HbA1c with continuation (median: –0.3 vs 0.1%; P = 0.04). Weight loss was greater when treatment continued (median: –1.8 vs 0.2 kg; P = 0.01), whereas blood pressure did not differ. No differences in safety endpoints were observed. Kidney function mildly, but significantly worsened with continuation (median estimated glomerular filtration rate [eGFR]: –2.7 vs 0 mL/min/1.73 m2; P = 0.03). Conclusions: Patients with T2DM and late-stage CKD had similar glucose control and safety profiles irrespective of SGLT2i continuation or discontinuation. This may favor clinical decision-making toward benefits of SGLT2i reduction in weight, cardiovascular events, CKD progression, and hospitalizations over potential safety concerns in these patients.