Journal
DIABETES OBESITY & METABOLISM
Volume 25, Issue 8, Pages 2151-2162Publisher
WILEY
DOI: 10.1111/dom.15091
Keywords
clinical trial; canagliflozin; SGLT2 inhibitor; type 2 diabetes; randomized trial; diabetes complications
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The aim of this study was to assess the risk of non-genital skin and soft tissue infections (SSTIs) associated with the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin. A post hoc analysis of two trials was conducted, and the results showed that canagliflozin did not significantly affect the risk of non-genital SSTIs or non-genital fungal SSTIs compared with placebo. This suggests that the changes in skin microenvironment mediated by SGLT2 inhibitors may not have meaningful clinical consequences.
Aims: To assess whether the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin affects risk of non-genital skin and soft tissue infections (SSTIs). Materials and methods: We performed a post hoc pooled individual participant analysis of the CANVAS Program and CREDENCE trials that randomized people with type 2 diabetes at high cardiovascular risk and/or with chronic kidney disease to either canagliflozin or placebo. Investigator-reported adverse events were assessed by two blinded authors following predetermined criteria for non-genital SSTIs. Risks of non-genital SSTIs, overall and within prespecified subgroups, and risk of non-genital fungal SSTIs, were analysed using Cox regression models. Factors associated with non-genital SSTIs were assessed using multivariable Cox regression models. Results: Overall, 903 of 14 531 participants (6%) experienced non-genital SSTIs over a median follow-up of 26 months. No difference was observed in non-genital SSTI rates between canagliflozin and placebo (24.0 events/1000 person-years vs. 23.9 events/1000 person-years, respectively; hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.85-1.11; P = 0.70), with consistent results across subgroups (all P interaction > 0.05). The risk of recurrent events and non-genital fungal infection also did not differ significantly between canagliflozin and placebo (HR 1.06, 95% CI 0.94-1.19 [P = 0.32] and HR 1.18, 95% CI 0.88-1.60 [P = 0.27], respectively). Baseline factors independently associated with non-genital SSTIs were younger age, male sex, higher body mass index, higher glycated haemoglobin, lower estimated glomerular filtration rate (eGFR), established peripheral vascular disease, and history of neuropathy. Conclusions: Canagliflozin did not affect risk of non-genital SSTIs or non-genital fungal SSTIs compared with placebo. These findings suggest that any SGLT2 inhibitormediated change in skin microenvironment is unlikely to have meaningful clinical consequences.
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