SGLT2 inhibitor use in patients with sarcoidosis was associated with a statistically significant reduction in all-cause mortality compared to propensity-matched non-users.
Cohort
Yes
Does SGLT2 inhibitor use reduce all-cause mortality and morbidity in adults with sarcoidosis?
In a real-world cohort of patients with sarcoidosis, SGLT2 inhibitor use was associated with reduced all-cause mortality and several morbidities, though with an increased risk of acute heart failure.
Abstract Introduction Recent evidence suggests that modulation of angiotensin type 1 (AT1) and type 2 (AT2) receptor activity, which is located in various organ systems but also expressed in alveolar epithelial cells, may contribute to anti-inflammatory and anti-fibrotic mechanisms that improve outcomes in advanced fibrotic lung diseases. SGLT2 inhibitors have been shown to influence these receptors through their effects on the renin-angiotensin-aldosterone system. Methods This retrospective cohort study used the TriNetX database to identify adults (≥18 years) diagnosed with sarcoidosis between January 1, 2015, and December 31, 2024. Patients were grouped based on SGLT2 inhibitor use initiated after diagnosis. Those with prior SGLT2 exposure, other granulomatous diseases, autoimmune conditions, or concurrent GLP-1 agonist therapy were excluded. One-to-one propensity score matching was performed for demographics, comorbidities, and concomitant medications, including ARBs and immunosuppressive agents. The primary outcome was all-cause mortality; secondary outcomes included sepsis, respiratory failure, cardiac arrest, acute myocardial infarction, acute heart failure, and acute kidney injury. Cox proportional hazards models were used to estimate hazard ratios, and the proportionality assumption was tested to ensure for model validity. Results SGLT2 inhibitor use was associated with a lower rate of all-cause mortality compared with patients not receiving these agents (Table 1). The SGLT2 group also showed reduced risks of sepsis, acute kidney injury, respiratory failure, and cardiac arrest. No significant difference was found for acute myocardial infarction, while an increase in acute heart failure was observed among SGLT2 users. Conclusion Our study showed a statistically significant improvement in mortality and several morbidity outcomes among patients receiving SGLT2 inhibitors. This builds on a finding from a prior study where SGLT2 inhibitors used with ARBs were linked to better outcomes compared to those only on ARB therapy. In our analysis, both groups were propensity-matched for ARB use, highlighting the independent benefit of SGLT2 inhibitors beyond their previously observed synergistic effect when combined with ARBs. These results call for further prospective studies and trials, including those exploring drugs that can modify angiotensin type 1 and type 2 receptor activity in a similar way, to assess whether this pathway can be a valid therapeutic target in advanced fibrotic lung diseases, including sarcoidosis. This abstract is funded by: None
Shama et al. (Fri,) conducted a cohort in Sarcoidosis. SGLT2 inhibitors vs. No SGLT2 inhibitors was evaluated on All-cause mortality. SGLT2 inhibitor use in patients with sarcoidosis was associated with a statistically significant reduction in all-cause mortality compared to propensity-matched non-users.
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