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We read with great interest the report on risk of incident diabetes mellitus among patients with non-alcoholic fatty liver disease by Mantovani et al.1 The bidirectional relationship between type 2 diabetes (T2D) and liver disease has been largely evaluated.2–4 However, optimal therapeutic options for T2D in patients with metabolic syndrome remain unclear. Several randomised trials have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2is) may have promising effects on early stages of liver disease, yet its effects on advanced liver disease are unclear and warrant further research.5–7 Although one observational study of patients with T2D and liver cirrhosis reported a 11% lower risk of hepatic decompensation events (HR 0.89, 95% CI 0.62 to 1.26) with SGLT2is versus dipeptidyl peptidase 4 inhibitors (DPP4is), it lacked statistical power by having wide CIs.8 Thus, we investigated the risk of hepatic events with SGLT2is among patients with T2D.
We conducted a large-scale, active comparator, new-user cohort study using the nationwide claims data of South Korea, which covers an entire population of >50 million.9 We included patients with T2D, newly prescribed an SGLT2i or a DPP4i between 2014 and 2020. We excluded patients aged<18 years; those with a history of end-stage renal disease or cancer; and those prescribed both SGLT2i and DPP4i on cohort entry. The primary outcome …
Contributors SB designed the overall research, collected the data, performed statistical analyses, interpreted the data and wrote the manuscript. HEJ designed the overall research, interpreted the data and contributed to the writing of the manuscript. SP contributed to the statistical analyses and writing of the manuscript. J-YS designed the study, supervised the statistical analyses and interpretation of data and critically revised the manuscript. OHYY, YC, JC, DHS and YMC critically revised the design and manuscript. J-YS as a guarantor of the study, accepts full responsibility for the result of this study, had access to the data and controlled the decision to publish.
Funding This research was supported by a grant (21183MFDS542) from the Ministry of Food and Drug Safety, South Korea, in 2021–2022.
Competing interests J-YS received grants from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation of Korea and pharmaceutical companies, including Daiichi Sankyo, GlaxoSmithKline and Pfizer, outside the submitted work.
Provenance and peer review Not commissioned; externally peer reviewed.
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