As well as improving metabolic outcomes, SGLT2 inhibitors may confer a protective effect against severe infections that require hospitalisation, including sepsis, pneumonia and gastrointestinal infections.
A Victorian study, published in Diabetes, Obesity and Metabolism [link here], compared infection outcomes in adults with type 2 diabetes initiated on SGLT2 inhibitors or DPP4 inhibitors following discharge from a public or private hospital between July 2013 and June 2018.
DPP4 inhibitors were used as the comparator as another class of second-line glucose-lowering medications for type 2 diabetes with no established association with infection-related outcomes.
The study identified 15,717 new users of SGLT2 inhibitors and 27,006 new users of DPP4 inhibitors and focussed on infections which have been shown to be more frequent and severe in people with diabetes.
It found new users of SGLT2 inhibitors had lower overall rates of infection-related hospitalisations than new users of DPP4 inhibitors (weighted incidence rate ratio (wIRR) 0.74).
Similarly, new users of SGLT2 inhibitors had lower rates of hospitalisations for sepsis (wIRR 0.60), pneumonia (wIRR 0.61), gastrointestinal infections (wIRR 0.77), UTI (wIRR 0.38), respiratory tract infections (wIRR 0.45), influenza (wIRR 0.63) and kidney infections (wIRR 0.49).
However new users of SGLT2 inhibitors had higher rates of hospitalisations for osteomyelitis (wIRR 1.14), foot infections (wIRR 1.25), and genital mycotic infections (wIRR 1.48) and no significant differences were observed in the rates of hospitalisations for cellulitis (wIRR).
“These findings have important implications because infections are a major burden among individuals with type 2 diabetes,” the study said. “Our results provide real-world evidence that can inform prescribing decisions around different infection risks.”
The investigators, from the Centre for Medicine Use and Safety at Monash University, said the observed association between SGLT2 inhibitor initiation and reduced risk of infection-related hospitalisations may be partially explained by effects on inflammation.
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“SGLT2 inhibitors have been shown to exert anti-inflammatory effects, possibly by addressing obesity and the release of pro-inflammatory mediators directly or through the oxidative balance pathway,” they said.
“Moreover, these benefits may also be mediated through improvements in glycaemic control and reductions in body weight, both of which may contribute to lower infection risk.”
They said their findings add to the growing body of evidence on the infection-related safety profile of SGLT2 inhibitors and provide important real-world insights for clinical decision-making.
However, they noted their cohort comprised individuals discharged from hospital and may therefore be sicker than the general type 2 diabetes population, potentially limiting extrapolation to community-based populations.
“Nevertheless, medications are often initiated at the point of hospital discharge and our findings relate to a high-risk group of individuals with type 2 diabetes.”
“Future studies may seek to evaluate temporal risk dynamics, such as the timing of infections after SGLT2 inhibitor initiation, to better understand temporal variations in risk and the clinical course of infection onset.”