Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with CKD and Type 2 Diabetes: Population-Based US Cohort Study

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Safety of sodium-glucose transporter 2 (SGLT-2) inhibitors in patients with type 2 diabetes: a meta-analysis of cohort studies

“…5.42 per 1,000 person-years), SGLT-2i was not associated with an increased risk of LLA (HR: 1.21, 95% CI: 0.96–1.52, p = 0.22, I 2 = 75.8%; Supplementary Appendix S5.5 ). The prevalence of PVD in these six studies ranged from 12.7% to 23.8% ( Ryan et al, 2018 ; Udell et al, 2018 ; Fralick et al, 2020 ; Lee et al, 2020 ; Udell et al, 2020 ; Patorno et al, 2021 ; Fu et al, 2023 ).…”

“…A total of 4,819 studies were retrieved, and 40 (n = 9,911,454) were included in the analysis ( Birkeland et al, 2017 ; Nyström et al, 2017 ; Tang et al, 2017 ; Wang et al, 2017 ; Persson et al, 2018 ; Ryan et al, 2018 ; Toulis et al, 2018 ; Udell et al, 2018 ; Yuan et al, 2018 ; Kim et al, 2018 ; Dave et al, 2019a ; Dawwas et al, 2019 ; Wang et al, 2019 ; Yang et al, 2019 ; Dave et al, 2019b ; Norhammar et al, 2019 ; Douros et al, 2020 ; Fralick et al, 2020 ; Lee et al, 2020 ; Udell et al, 2020 ; Laursen et al, 2021 ; Yu et al, 2020 ; Han et al, 2021 ; Patorno et al, 2021 ; Han et al, 2021 ; Fralick et al, 2021b ; Fralick et al, 2021b ; Laursen et al, 2021 ; Ryan et al, 2018 ; Caparrotta et al, 2021 ; Bhosle et al, 2022 ; Laursen et al, 2021 ; Fralick et al, 2020 ; Schneeweiss et al, 2021, Al-et al 2022, Ha et al, 2022 ; van Dalem et al, 2022 ; D'Andrea et al, 2023 ; Fu et al, 2023 ; Htoo et al, 2023 ). Figure 1 shows the literature selection flowchart.…”

“…Fourteen studies compared the safety of the SGLT-2i class and oGLD in terms of DKA among the 40 trials that met the inclusion criteria ( Kim et al, 2018 ; Han et al, 2021 ; Fralick et al, 2021a ; Douros et al, 2020 ; Patorno et al, 2021 ; Tang et al, 2017 ; Laursen et al, 2021 ; Fralick et al, 2021b ; Toulis et al, 2018 ; Patorno et al, 2021 ; Laursen et al, 2021 ; Bhosle et al, 2022 ; D'Andrea et al, 2023 ; Fu et al, 2023 ). A total of 2,665 DKA cases were reported among 1,233,569 patients treated with SGLT-2i (mean incidence rate 2.86 per 1,000 person-years).…”

“…Eighteen studies were included in the assessment of the safety of SGLT-2i versus oGLD in terms of LLA ( Fralick et al, 2021b ; Fralick et al, 2019 ; Yang et al, 2019 ; Ueda et al, 2018 ; Udell et al, 2018 ; Ryan et al, 2018 ; Dawwas et al, 2019 ; Chang et al, 2018 ; Caparrotta et al, 2021 ; Wang et al, 2019 ; Persson et al, 2018 ; Udell et al, 2020 ; Wang et al, 2019 ; Dawwas et al, 2019 ; Dave et al, 2019a ; Dave et al, 2019b ; D'Andrea et al, 2023 ; Fu et al, 2023 ). Among these studies, 2,025 LLA cases were reported in the SGLT-2i group (mean incidence rate 2.30 per 1,000 person-years).…”

Relative and Absolute Risks of Adverse Events with Real-World Use of SGLT2 Inhibitors in CKD

“…Real-world studies are important to inform the safety profile of these agents and guide the use of these medications outside of a clinical trial. In this issue of CJASN , Fu et al 7 have conducted an important pharmacoepidemiology study examining the comparative safety of SGLT2is as compared with glucagon-like peptide-1 receptor agonists (GLP1RAs) in people with type 2 diabetes and CKD stages 3–4, diagnosed on the basis of International Classification of Diseases codes. The authors demonstrate that SGLT2is were associated with a three-fold relative risk increase in genital infections (absolute risk increase [ARI], 41 per 1000 py), a 65% increased risk in lower limb amputations (ARI, 2.5 per 1000 py), and a 30% increase in nonvertebral fractures (ARI, 2.1 per 1000 py) as compared with GLP1RAs.…”