The impacts of SGLT2 inhibitors on the mortality of patients with tuberculosis

Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) have been utilized since 2013 as a treatment for type 2 diabetes mellitus (DM), lowering blood glucose by promoting urinary glucose excretion. Beyond glycemic control, research has shown that SGLT2-i can reduce inflammatory markers such as CRP and TNF-α, and also lower all-cause and cardiovascular mortality. Evidence also suggests a possible cardioprotective role in diabetic cardiomyopathy and ischemic heart disease. While SGLT2-i are associated with an increased risk of genital infections, they may reduce respiratory infections and pneumonia-related deaths. Considering the high tuberculosis (TB) mortality in diabetic patients, the potential for SGLT2-i to reduce TB mortality warrants investigation, though no previous studies have addressed this directly.

To explore this, a large-scale retrospective cohort study was conducted using Taiwan’s National Health Insurance Research Database (NHIRD), covering over 99% of the population. The study identified new-onset TB patients from 2017 to 2020, defining TB cases by ICD-10-CM codes and anti-TB drug prescriptions. Patients using SGLT2-i were compared with matched controls who did not use these drugs, applying a 1:4 propensity score matching based on age, sex, and comorbidities. Those under 20, with pre-existing SGLT2-i use before TB diagnosis, or with incomplete data were excluded.

Out of 34,820 TB patients, 345 were SGLT2-i users. After matching, 1,380 non-users were selected for comparison. Demographically, SGLT2-i users had higher rates of DM, hyperlipidemia, and hypertension, whereas non-users had more COPD. Notably, one-year mortality was significantly lower in SGLT2-i users (8.1%) compared to non-users (17.5%), with a longer average time to death and follow-up duration observed in the SGLT2-i group. These trends remained consistent even after matching for baseline characteristics.

Further analyses showed that SGLT2-i use was associated with significantly reduced one-year mortality, with adjusted hazard ratios around 0.42 both before and after matching. Dose-dependent effects were observed: high-dose SGLT2-i users had markedly lower mortality compared to non-users, with adjusted HRs as low as 0.08. In contrast, low-dose users showed a non-significant trend toward reduced mortality. These findings were robust even when stratified by individual drugs, with dapagliflozin and empagliflozin both showing significant protective effects, while canagliflozin did not.

In summary, this study provides the first large-scale evidence that SGLT2-i use in TB patients with diabetes may significantly reduce one-year mortality, particularly at higher cumulative doses. The data suggest that certain SGLT2 inhibitors, notably dapagliflozin and empagliflozin, are especially effective. These findings highlight the potential of SGLT2-i not only for glycemic control and cardiovascular benefits but also for improving TB-related outcomes, paving the way for further clinical investigations and potential therapeutic strategies. 

Source: Lee, C.S., Ho, C.H., Liao, K.M., Wu, Y.C. and Shu, C.C., 2025. The impacts of SGLT2 inhibitors on the mortality of patients with tuberculosis. Journal of Infection and Public Health, p.102686.