Acute kidney injury in patients on SGLT2 inhibitors: a propensity-matched analysis
Open accessAbstract
OBJECTIVE: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are new medications that improve cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). However, the Food and Drug Administration has issued alerts regarding increased acute kidney injury (AKI) risk with canagliflozin and dapagliflozin. We aimed to assess the real-world risk of AKI in new SGLT2 inhibitor users in two large health care utilization cohorts of patients with T2D. RESEARCH DESIGN AND METHODS: We used longitudinal data from the Mount Sinai chronic kidney disease registry and the Geisinger Health System cohort. We selected SGLT inhibitor users and nonusers (patients with T2D without SGLT2 inhibitor prescription). We determined AKI by the KDIGO (Kidney Disease: Improving Global Outcomes) definition (AKIKDIGO). We performed 1:1 nearest-neighbor propensity matching and calculated unadjusted hazard ratios (HRs) and adjusted HRs (aHRs; accounting for covariates poorly balanced) for AKI in primary and sensitivity analyses. RESULTS: We identified 377 SGLT2 inhibitor users and 377 nonusers in the Mount Sinai cohort, of whom 3.8 and 9.7%, respectively, had an AKIKDIGO event over a median follow-up time of 14 months. The unadjusted hazards of AKIKDIGO were 60% lower in users (HR 0.4 [95% CI 0.2–0.7]; P = 0.01), which was unchanged (aHR 0.4 [95% CI 0.2–0.7]; P = 0.004) postadjustment. Similarly, we identified 1,207 SGLT2 inhibitor users and 1,207 nonusers in the Geisinger cohort, of whom 2.2 and 4.6% had an AKIKDIGO event. AKIKDIGO unadjusted hazards were lower in users (HR 0.5 [95% CI 0.3–0.8]; P < 0.01) with modest attenuation postadjustment for covariates (aHR 0.6 [95% CI 0.4–1.1]; P = 0.09). These estimates did not qualitatively change across several sensitivity analyses. CONCLUSIONS: Our findings do not suggest an increased risk of AKI associated with SGLT2 inhibitor use in patients with T2D in two large health systems.
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SGLT2 inhibitors have not been found to promote AKI in randomized controlled trials of advanced kidney disease or high cardiovascular risk with normal kidney function.
“There was concern that sodium-glucose cotransporter 2 (SGLT2) inhibitors may promote AKI through volume depletion, particularly when combined with diuretics or other medications that reduce glomerular filtration; however, this has not been found to be true in randomized controlled trials of advanced kidney disease (29) or high CVD risk with normal kidney function (30)(31)(32).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [30]
The Conclusions (page not provided) report that EMPA-REG OUTCOME found no increased AKI risk among participants with baseline eGFR >60, and that canagliflozin trials found no significant difference in renal-related adverse events versus placebo. But this source is itself a propensity-matched observational study, not a randomized trial; it reports those trial findings rather than generating them. (LLM, conf=0.85)
Experimental — accuracy not yet measuredConcern that SGLT2 inhibitors may promote AKI through volume depletion has not been found to be true in randomized controlled trials of advanced kidney disease or high CVD risk with normal kidney function.
“There was concern that sodium-glucose cotransporter 2 (SGLT2) inhibitors may promote AKI through volume depletion, particularly when combined with diuretics or other medications that reduce glomerular filtration; however, this has not been found to be true in randomized controlled trials of advanced kidney disease (29) or high CVD risk with normal kidney function (30)(31)(32).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [30]
The Conclusions describe volume depletion as a possible AKI mechanism and report that EMPA-REG OUTCOME and other randomized trials did not show increased AKI risk. But this paper’s own analysis is observational, and it describes trials focused on chronic kidney disease as ongoing; it does not establish the claim about completed randomized trials in advanced kidney disease. (LLM, conf=0.88)
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- Authors
- Nadkarni, G. N., Ferrandino, R., Chang, A., Surapaneni, A., Chauhan, K., Poojary, P., Saha, A., Ferket, B., Grams, M. E., & Coca, S. G.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Division of Nephrology, Geisinger Medical Center, Danville, PA
- Johns Hopkins University (US)
- Corresponding author
- Nadkarni, Girish N.
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2017-08-21
- Volume
- 40
- Issue
- 11
- Pages
- 1479-1485
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC5652593
- OpenAlex
- W2749798950
- Semantic Scholar
- de92a99751bdad17b45d0ca2e8845addc558afe6
- Cited by
- 188
- References
- 19
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 18 · 2023: 23 · 2022: 21 · 2021: 21 · 2020: 32 · 2019: 27 · 2018: 17 · 2017: 3 · 2015: 1
- FWCI
- 19.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Care (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (K23-DK-107908, K23-DK-1065501, R01-DK-096549, U01-DK-106962)
- Topics
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- acute kidney injury, SGLT2 inhibitors, type 2 diabetes, canagliflozin, dapagliflozin, drug safety, chronic kidney disease, adverse drug reactions, KDIGO criteria, renal outcomes, cardiovascular outcomes, health care utilization, health care costs
- MeSH terms
- Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Aged, Benzhydryl Compounds, Blood Pressure, Cholesterol, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Glucosides, Hemoglobins, Humans, Hypoglycemic Agents, Kidney, Longitudinal Studies, Male, Middle Aged, Retrospective Studies, Sensitivity and Specificity, Body Mass Index, Incidence, Sodium-Glucose Transporter 2, Acute Kidney Injury
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