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Sodium glucose co-transporter-2 inhibitors in intensive care unit patients with type 2 diabetes: a pilot case control
Johan Mårtensson1,2, Salvatore Lucio Cutuli3,4, Eduardo A Osawa5
1Department of Physiology and Pharmacology, Section of Anaesthesia and Intensive Care, Karolinska Institutet, Stockholm, Sweden. johan.martensson@regionstockholm.se.
Background:
Sodium 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.
Methods:
We 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.
Results:
Median (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).
Conclusions:
In 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.
Insights
This pilot study found that empagliflozin in ICU patients with type 2 diabetes increased sodium and chloride levels. However, it did not significantly affect acid-base balance, hypoglycemia, ketoacidosis, kidney function, or mortality.
Area of Science:
- Intensive Care Medicine
- Endocrinology
- Nephrology
Background:
- Sodium glucose co-transporter-2 (SGLT2) inhibitors are known to improve cardiovascular and renal outcomes in type 2 diabetes.
- The safety and efficacy of SGLT2 inhibitors in critically ill patients with type 2 diabetes admitted to the Intensive Care Unit (ICU) remain uncertain.
- This pilot study investigates the use of empagliflozin in this specific patient population.
Purpose of the Study:
- To assess the safety and biochemical effects of empagliflozin in ICU patients with type 2 diabetes.
- To evaluate the relationship between empagliflozin therapy and clinical outcomes, including electrolyte and acid-base parameters, hypoglycemia, ketoacidosis, kidney function, and mortality.
- To provide preliminary data for future larger-scale studies.
Main Methods:
- A pilot study comparing 18 ICU patients with type 2 diabetes receiving empagliflozin (10 mg daily) and insulin (treatment group) to 72 matched controls not receiving empagliflozin.
- Both groups were managed under a liberal glucose control protocol targeting 10-14 mmol/l.
- Key outcomes assessed included changes in electrolytes, acid-base status, incidence of hypoglycemia, ketoacidosis, worsening kidney function, positive urine cultures, and hospital mortality.
Main Results:
- Empagliflozin therapy was associated with a statistically significant increase in maximum sodium levels (P=0.045) and a trend towards increased chloride levels (P=0.059).
- No significant differences were observed in acid-base parameters, hypoglycemia, ketoacidosis, worsening kidney function, bacteriuria, or hospital mortality between the empagliflozin and control groups.
- Specifically, 6% of patients in each group experienced hypoglycemia, one control patient developed ketoacidosis, and hospital mortality was 17% in the treatment group versus 19% in the control group.
Conclusions:
- In this pilot study, empagliflozin therapy in ICU patients with type 2 diabetes was associated with increased sodium and chloride levels.
- Empagliflozin did not appear to be significantly associated with adverse acid-base changes, hypoglycemia, ketoacidosis, worsening kidney function, or increased mortality in this cohort.
- Further research is warranted to confirm these findings in a larger patient population.
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