BackgroundSodium glucose co-transporter-2 (SGLT2) inhibitors improve long-term cardiovascular and renal outcomes in individuals with type 2 diabetes. However, the safety of SGLT2 inhibitors in ICU patients with type 2 diabetes is uncertain. We aimed to perform a pilot study to assess the relationship between empagliflozin therapy and biochemical, and clinical outcomes in such patients.MethodsWe included 18 ICU patients with type 2 diabetes receiving empagliflozin (10 mg daily) and insulin to target glucose range of 10–14 mmol/l according to our liberal glucose control protocol for patients with diabetes (treatment group). Treatment group patients were matched on age, glycated hemoglobin A1c, and ICU duration with 72 ICU patients with type 2 diabetes exposed to the same target glucose range but who did not receive empagliflozin (control group). We compared changes in electrolyte and acid–base parameters, hypoglycemia, ketoacidosis, worsening kidney function, urine culture findings, and hospital mortality between the groups.ResultsMedian (IQR) maximum increase in sodium and chloride levels were 3 (1–10) mmol/l and 3 (2–8) mmol/l in the control group and 9 (3–12) mmol/l and 8 (3–10) mmol/l in the treatment group (P= 0.045 for sodium,P= 0.059 for chloride). We observed no differences in strong ion difference, pH or base excess. Overall, 6% developed hypoglycemia in each group. No patient in the treatment group and one patient in the control group developed ketoacidosis. Worsening kidney function occurred in 18% and 29% of treatment and control group patients, respectively (P= 0.54). Urine cultures were positive in 22% of treatment group patients and 13% of control group patients (P= 0.28). Overall, 17% of treatment group patients and 19% of control group patients died in hospital (P= 0.79).ConclusionsIn our pilot study of ICU patients with type 2 diabetes, empagliflozin therapy was associated with increases in sodium and chloride levels but was not significantly associated with acid–base changes, hypoglycemia, ketoacidosis, worsening kidney function, bacteriuria, or mortality.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13054-023-04481-y.