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Do SGLT2 inhibitors protect against pneumonia and sepsis?

Reductions in pneumonia and sepsis, as well as death due to infection, seen with SGLT2 inhibitors versus DPP-4 inhibitors.

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.

Click here to read the study in full.


Wu MZ, Chandramouli C, Wong PF et al (2022) Risk of sepsis and pneumonia in patients initiated on SGLT2 inhibitors and DPP-4 inhibitors. Diabetes Metab 23 Jun [Epub ahead of print]. doi: 10.1016/j.diabet.2022.101367

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