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. 2025 Mar 18:zwaf156.
doi: 10.1093/eurjpc/zwaf156. Online ahead of print.

Effect of SGLT2i on kidney outcomes of individuals with type2 diabetes according to blood pressure levels

Takahiro Jimba  1 , Hidehiro Kaneko  1   2 , Yuta Suzuki  1 , Akira Okada  3 , Tatsuhiko Azegami  4 , Toshiyuki Ko  1 , Katsuhito Fujiu  1   2 , Hiroyuki Morita  1 , Norifumi Takeda  1 , Kaori Hayashi  4 , Takashi Yokoo  5 , Koichi Node  6 , Issei Komuro  1   7   8 , Hideo Yasunaga  9 , Masaomi Nangaku  10 , Norihiko Takeda  1
Affiliations

Effect of SGLT2i on kidney outcomes of individuals with type2 diabetes according to blood pressure levels

Takahiro Jimba et al. Eur J Prev Cardiol. .

Abstract

Aims: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have proven kidney protective effects. Given that the SGLT2 inhibitors lower blood pressure (BP), the magnitude of their kidney benefits may vary depending on an individual's BP. Therefore, we investigated whether baseline BP modifies the effect of SGLT2 inhibitors on kidney function.

Methods: This study included individuals with SGLT2 inhibitors or dipeptidyl peptidase-4 (DPP4) inhibitors newly prescribed for type 2 diabetes using a nationwide epidemiological cohort and performed propensity score matching (1:2). The primary outcome was the annual eGFR decline. We further investigated the interaction effect of systolic BP (sBP) at the time of prescription using a 3-knot restricted cubic spline model.

Results: We analyzed 2,148 individuals with SGLT2 inhibitor prescriptions and 4,296 matched individuals with DPP4 inhibitor prescriptions. Overall, the annual eGFR decline was less pronounced in the SGLT2 inhibitor group than in the DPP4 inhibitor group (-1.32 ml/min/1.73 m2 vs -1.50 ml/min/1.73 m2). The treatment effect of SGLT2 inhibitors over DPP4 inhibitors was augmented with higher sBP (p for interaction = 0.0199). Further, after adjusting the definition of outcomes to a 30% or 40% reduction in eGFR, the advantages of SGLT2 inhibitors persisted, with a trend of augmented effect with higher sBP. Notably, annual eGFR decline was exacerbated for females presented with lower sBP when treated with SGLT2 inhibitors compared to DPP4 inhibitors.

Conclusions: This nationwide cohort analysis demonstrated that the kidney protective effect of SGLT2 inhibitors could be modified by baseline sBP, highlighting the importance of patient selection by assessing their BP.

Keywords: Blood pressure; Diabetes; Estimated glomerular filtration rate decline; SGLT2 inhibitor.

Plain language summary

In the Japanese nationwide epidemiological cohort, the present study demonstrated that the SGLT2 inhibitors reduced the decrease in annual eGFR for individuals with diabetes, and these effects were augmented in individuals with higher systolic BP. SGLT2 inhibitors reduced the decrease in annual eGFR for individuals with diabetes compared to DPP4 inhibitors, across a wide spectrum of baseline BP in real-world settings.We first demonstrated that this kidney protective effect of SGLT2 inhibitors was augmented in individuals with higher baseline systolic BP.

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