This retrospective, observational study used registry data from Hong Kong to compare the incidence and outcomes of pneumonia and sepsis in new users of SGLT2 inhibitors versus DPP-4 inhibitors. Adults with type 2 diabetes who initiated either drug class between January 2015 and December 2019 were followed up until 31 January 2021. SGLT2i users were propensity score-matched with DPP-4i users in a 1:2 ratio.
The propensity score-matched cohort comprised 10,706 and 18,281 users of SGLT2is and DPP-4is, respectively (mean age, 60 years; 61% male). Over a median follow-up of 2.3 years, the incidence rate of pneumonia was significantly lower in SGLT2i users (11.4 vs 20.5 per 1000 person-years; adjusted hazard ratio [HR], 0.63), regardless of diabetes duration. Similarly, the incidence rate of sepsis was lower with SGLT2is (6.0 vs 12.9 per 1000 person-years; HR=0.52).
Outcomes also favoured the SGLT2i class, with lower risks of death related to pneumonia (HR, 0.41), sepsis (HR, 0.39) and infectious diseases (HR, 0.43). Perhaps surprisingly, SGLT2i users also had a lower risk of urinary tract infections (HR, 0.59) and a similar risk of urogenital infections compared with DPP-4i users.
Subgroup analysis showed consistent effects when stratifying users by age (≤60 vs >60 years); sex; cardiovascular disease status; eGFR (≥60 vs <60 mL/min/1.73 m2); HbA1c (<53 vs ≥53 mmol/mol); type of SGLT2i; and concomitant use of other diabetes therapies, statins and aspirin.
The authors conclude that SGLT2 inhibitors are associated with a substantially lower risk of pneumonia, sepsis and deaths due to these conditions. Proposed mechanisms to explain this include anti-inflammatory effects as well as indirect effects of the cardiorenal protection afforded by SGLT2is.
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