T2DM: SGLT2 inhibitors associated with lower rates of ICU admission and all-cause mortality

A retrospective observational study of nearly 28,000 patients with type 2 diabetes mellitus (T2DM) in Hong Kong finds that use of sodium-glucose cotransporter 2 (SGLT2) inhibitors is independently associated with lower rates of ICU admission and all-cause mortality across various disease categories.

“SGLT2 inhibitors’ benefits with respect to reducing the rates of adverse cardiac and renal outcomes in patients with T2DM have been well described in randomized trials,” wrote the researchers. [N Engl J Med 2015;373:2117-2128; N Engl J Med 2017;377:644-657; N Engl J Med 2019;380:347-357] “The objective of the present study was to determine whether SGLT2 inhibitors had any impact on the overall burden of critical illness.”

After 1:2 propensity score matching, the researchers compared the risks and causes of ICU admission, severity of illness, and mortality associated with incidental use of SGLT2 inhibitors (n=10,308) and dipeptidyl peptidase-4 (DPP-4) inhibitors (n=10,308) among T2DM patients whose data were available on Hong Kong’s Clinical Data Analysis and Reporting System. The mean age of the cohort was 59 ± 11 years, and 62.3 percent of patients were male. Apart from certain oral antidiabetic agents, all variables were well balanced between groups with standardized difference <0.1. The median follow-up period was 2.9 years. [Crit Care Med 2023;doi:10.1097/CCM.0000000000005869]

Critical illness requiring ICU admission occurred in 2.8 percent vs 3.7 percent of patients in the SGLT2 inhibitor vs DPP-4 inhibitor group. “The risk of ICU admission was lower in SGLT2 inhibitor vs DPP-4 inhibitor users [hazard ratio (HR), 0.79; 95 percent confidence interval (CI), 0.69–0.91; p=0.001], translating to a number needed to treat [NNT] of 114,” reported the researchers.

The severity of illness upon ICU admission was lower in SGLT2 inhibitor vs DPP-4 inhibitor users (median predicted risk of death, 0.08 [95 percent CI, 0.03–0.25] vs 0.14 [95 percent CI, 0.05–0.36]; p<0.001). While the risk of emergency ICU admission was lower among SGLT2 inhibitor vs DPP-4 inhibitor users (2.0 percent vs 2.8 percent; HR, 0.75; 95 percent CI, 0.64–0.89; p=0.001), as was the risk of nonoperative ICU admission (1.5 percent vs 2.4 percent; HR, 0.66; 95 percent CI, 0.54–0.79; p<0.001), the length of ICU stay was similar between the two groups.

Admissions for sepsis were fewer in SGLT2 inhibitor vs DPP-4 inhibitor users (0.4 percent vs 0.8 percent; HR, 0.61; 95 percent CI, 0.43–0.85; p=0.004). “The 40 percent reduction in ICU admission due to sepsis is striking. If this finding is confirmed in follow-up prospective trials, it could have significant implications, as sepsis accounts for up to 6 percent of infection-related hospitalizations and 12 percent of infection-related deaths in the diabetic population,” commented the researchers. [Diabetes Care 2018;41:513-521]

All-cause mortality occurred in 3.1 percent vs 7.5 percent of patients in the SGLT2 inhibitor vs DPP-4 inhibitor group. The risk of death was lower in SGLT2 inhibitor vs DPP-4 inhibitor users (HR, 0.44; 95 percent CI, 0.38–0.49; p<0.001), translating to a NNT of 22. The risks of mortality due to infectious (0.6 percent vs 2.3 percent; HR, 0.26; 95 percent CI, 0.20–0.34; p<0.001), cardiovascular (1.0 percent vs 1.9 percent; HR, 0.58; 95 percent CI, 0.46–0.72; p<0.001) or renal (0.03 percent vs 0.14 percent; HR, 0.22; 95 percent CI, 0.07–0.73; p=0.014) causes were lower in SGLT2 inhibitor vs DPP-4 inhibitor users.