Scholarlink

Background <p>Sodium–glucose cotransporter-2 inhibitors (SGLT2is) reduce the risk of acute kidney injury (AKI) in diverse populations; however, their effects on drug-induced AKI remain unclear. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a major cause of nephrotoxicity, and combining them with renin–angiotensin–aldosterone system inhibitors and diuretics increases the risk. Given the natriuretic action of SGLT2is, their impact on NSAID-related AKI requires evaluation.</p> Methods <p>We performed this retrospective cohort study using the nationwide Japanese claims database (2015–2023). Adults with type 2 diabetes initiated on NSAIDs while receiving either SGLT2is or dipeptidyl peptidase-4 inhibitors (DPP4is) were included. Inverse probability of treatment weighting balanced 60 covariates. The primary outcome was 90-day AKI, identified by International Classification of Diseases 10th edition codes, and the secondary outcomes were 30-day risk and on-treatment incidence during NSAID use.</p> Results <p>We identified 39,251 SGLT2i and 256,298 DPP4i users. After weighting, the covariates were well balanced. The occurrence rates of 90-day AKI were 0.17% and 0.24% in SGLT2i and DPP4i users, respectively (risk ratio 0.70, 95% confidence interval: 0.62–0.79). Consistent protection was observed at 30 days and during on-treatment exposure. Subgroup analyses showed greater benefit in younger patients and those with chronic kidney disease, higher BMIs, and shorter exposure. None of the subgroups demonstrated excess risk.</p> Conclusions <p>SGLT2i therapy was associated with a significantly lower risk of NSAID-induced AKI than DPP4is. These findings indicate an observed association between SGLT2i therapy and a lower incidence of drug-induced nephrotoxicity, which may inform safer NSAID prescribing in patients with type 2 diabetes.</p> Clinical trial number <p>Not applicable.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Effects of SGLT2 inhibitors on NSAID-associated acute kidney injury in type 2 diabetes: a claims-based cohort study

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月16日

查看全文
  • Yuki Kunitsu,
  • Hiroyoshi Koide,
  • Keiko Ikuta,
  • Daiki Hira,
  • Shunsaku Nakagawa,
  • Masahiro Tsuda,
  • Shin-Ya Morita,
  • Tomohiro Terada

摘要

Background

Sodium–glucose cotransporter-2 inhibitors (SGLT2is) reduce the risk of acute kidney injury (AKI) in diverse populations; however, their effects on drug-induced AKI remain unclear. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a major cause of nephrotoxicity, and combining them with renin–angiotensin–aldosterone system inhibitors and diuretics increases the risk. Given the natriuretic action of SGLT2is, their impact on NSAID-related AKI requires evaluation.

Methods

We performed this retrospective cohort study using the nationwide Japanese claims database (2015–2023). Adults with type 2 diabetes initiated on NSAIDs while receiving either SGLT2is or dipeptidyl peptidase-4 inhibitors (DPP4is) were included. Inverse probability of treatment weighting balanced 60 covariates. The primary outcome was 90-day AKI, identified by International Classification of Diseases 10th edition codes, and the secondary outcomes were 30-day risk and on-treatment incidence during NSAID use.

Results

We identified 39,251 SGLT2i and 256,298 DPP4i users. After weighting, the covariates were well balanced. The occurrence rates of 90-day AKI were 0.17% and 0.24% in SGLT2i and DPP4i users, respectively (risk ratio 0.70, 95% confidence interval: 0.62–0.79). Consistent protection was observed at 30 days and during on-treatment exposure. Subgroup analyses showed greater benefit in younger patients and those with chronic kidney disease, higher BMIs, and shorter exposure. None of the subgroups demonstrated excess risk.

Conclusions

SGLT2i therapy was associated with a significantly lower risk of NSAID-induced AKI than DPP4is. These findings indicate an observed association between SGLT2i therapy and a lower incidence of drug-induced nephrotoxicity, which may inform safer NSAID prescribing in patients with type 2 diabetes.

Clinical trial number

Not applicable.