Effects of dapagliflozin in stage 4 chronic kidney disease
Open accessAbstract
Significance Statement: Relatively little is known about the relative safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with advanced (stage 4) CKD. The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial enrolled patients with CKD with or without type 2 diabetes (mean eGFR 43 ± 12 ml/min per 1.73m 2 ), finding that patients receiving the drug had lower risks of major kidney and cardiovascular events and an attenuation of progressive eGFR loss compared with patients receiving placebo. In this analysis within a subgroup of patients with stage 4 CKD and albuminuria, the authors found that the benefits of the SGLT2 inhibitor dapagliflozin in patients with baseline eGFR<30 ml/min per 1.73m 2 were consistent with those observed in the DAPA-CKD trial overall, with no evidence of increased risks. Background: In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized, placebo-controlled trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin significantly reduced risk of kidney failure and prolonged survival in patients with CKD with or without type 2 diabetes. Methods: Adults with eGFR of 25–75 ml/min per 1.73 m 2 and urinary albumin-to-creatinine ratio of 200–5000 mg/g had been randomized to receive dapagliflozin 10 mg/d or placebo. Here, we conducted a prespecified analysis of dapagliflozin’s effects in patients with stage 4 CKD (eGFR,30 ml/min per 1.73 m 2 ) at baseline. The primary end point was a composite of time to ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Secondary end points were a kidney composite (same as the primary end point but without cardiovascular death), a composite of cardiovascular death or heart failure hospitalization, and all-cause death. Results: A total of 293 participants with stage 4 CKD received dapagliflozin and 331 received placebo. Patients with stage 4 CKD randomized to dapagliflozin experienced a 27% (95% confidence interval [95% CI]: −2 to 47%) reduction in the primary composite endpoint, and 29% (−2 to 51%), 17% (−53 to 55%), and 32% (−21 to 61%) reductions in the kidney, cardiovascular and mortality endpoints, respectively, relative to placebo. Interaction P-values were 0.22, 0.13, 0.63, and 0.95, respectively, comparing CKD stages 4 versus 2/3. The eGFR slope declined by 2.15 and 3.38 ml/min per 1.73 m 2 per year in the dapagliflozin and placebo groups, respectively ( P =0.005). Patients treated with dapagliflozin or placebo had similar rates of serious adverse events and adverse events of interest. Conclusions: Among patients with stage 4 CKD and albuminuria, the effects of dapagliflozin were consistent with those observed in the DAPA-CKD trial overall, with no evidence of increased risks.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
SGLT2 inhibitors are safe and effective at eGFR levels of >20 mL/min/1.73m2.
“Subgroup analyses from DAPA-CKD (117) and analyses from the EMPEROR heart failure trials suggest that SGLT2 inhibitors are safe and effective at eGFR levels of >20 mL/min/1.73m 2 .”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [117]
The Abstract and Discussion report benefits of dapagliflozin in stage 4 CKD without increased adverse-event rates. But DAPA-CKD enrolled participants with baseline eGFR of at least 25 mL/min/1.73 m², so its subgroup analysis does not itself establish safety and effectiveness throughout the claimed range above 20; the Discussion attributes enrollment down to 20 to EMPEROR-Reduced. (LLM, conf=0.85)
Experimental — accuracy not yet measuredPost hoc analyses of CREDENCE and DAPA-CKD demonstrated that participants who met eGFR eligibility at screening but subsequently had lower baseline eGFR prior to randomization experienced similar kidney benefits as those with baseline eGFR above eligibility thresholds.
“In addition, post hoc analyses of CREDENCE and DAPA-CKD demonstrated that participants who met eGFR eligibility at screening but subsequently had lower baseline eGFR prior to randomization ( < 30 ml/min per 1.73 m 2 and < 25 ml/min per 1.73 m 2 , respectively) experienced similar kidney bene fi ts as those with baseline eGFR above eligibility thresholds.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [141]
Supplemental Figure S1 says 60 DAPA-CKD participants had baseline eGFR below 25 despite meeting the screening criterion. The Results compare kidney outcomes for baseline eGFR below versus at least 30, not below versus at least 25; the Statistical Analyses section calls that stage-based comparison prespecified. The Discussion reports a CREDENCE stage 4 finding but does not establish the claimed comparison with participants above its screening threshold. (LLM, conf=0.87)
Experimental — accuracy not yet measuredSubgroup analyses from DAPA-CKD and analyses from the EMPEROR heart failure trials suggest that SGLT2 inhibitors are safe and effective at eGFR levels of >20 mL/min/1.73m2.
“Subgroup analyses from DAPA-CKD (133) and analyses from the EMPEROR heart failure trials suggest that SGLT2 inhibitors are safe and effective at eGFR levels of >20 mL/min/ 1.73 m 2 .”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [133]
The paper’s stage 4 DAPA-CKD analysis reports benefits without increased adverse-event risks, supporting safety and effectiveness in that subgroup. But the Abstract states that DAPA-CKD enrolled participants with baseline eGFR of 25–75 mL/min/1.73 m²; its subgroup analysis does not establish those findings across the full range above 20. The Discussion attributes enrollment down to 20 to EMPEROR-Reduced, not DAPA-CKD. (LLM, conf=0.85)
Experimental — accuracy not yet measuredA post hoc analysis of the DAPA-CKD trial demonstrated that in individuals with stage G4 CKD and albuminuria, the effects of dapagliflozin were consistent with those observed in the trial overall, with no evidence of increased risks.
“A post hoc analysis of the DAPA-CKD trial demonstrated that in individuals with stage G4 CKD and albuminuria, the effects of dapagliflozin were consistent with those observed in the trial overall, with no evidence of increased risks (133).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [133]
The Abstract and concluding passage report that, among patients with stage 4 CKD and albuminuria, dapagliflozin's effects were consistent with the overall DAPA-CKD trial, with no evidence of increased risks. However, the Abstract calls this stage 4 analysis prespecified; the Post Hoc Exploratory Sub-Subgroup Analyses section applies “post hoc” to further analyses within that subgroup, not to the analysis described in the claim. (LLM, conf=0.90)
Experimental — accuracy not yet measuredSubgroup analyses of participants in CREDENCE and DAPA-CKD with baseline eGFR <30 mL/min/1.73 m2 provide additional support for SGLT2 inhibitor use.
“Additional support comes from subgroup analyses of participants in the CREDENCE and DAPA-CKD trials with baseline eGFR <30 mL/min/1.73 m2 (59,60).”
Subgroup analyses of individual trials and meta-analyses have consistently demonstrated kidney and cardiovascular benefits of SGLT2i across eGFR categories, including participants with eGFR <30 ml/min per 1.73 m2 and participants without albuminuria.
“Subgroup analyses of individual trials and meta-analyses have consistently demonstrated kidney and cardiovascular benefits across eGFR categories, including participants with eGFR <30 ml/min per 1.73 m 2 and participants without albuminuria.16,17”
Efficacy and safety data from EMPA-KIDNEY and DAPA-CKD combined include information on nearly 3000 patients with an eGFR of 20-30 mL/min per 1·73 m2.
“efficacy and safety data from EMPA-KIDNEY and DAPA-CKD combined include information on nearly 3000 patients with an eGFR of 20–30 mL/min per 1·73 m2.”
A total of 489 kidney disease progression outcomes accrued in those with an eGFR less than 30 mL/min per 1·73 m2 in EMPA-KIDNEY and DAPA-CKD.
“A total of 489 kidney disease progression outcomes accrued in those with an eGFR less than 30 mL/min per 1·73 m2 in those two trials.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 28 · Cited by 201
- Authors
- Chertow, G. M., Vart, P., Jongs, N., Toto, R. D., Gorriz, J. L., Hou, F. F., McMurray, J. J. V., Correa-Rotter, R., Rossing, P., Sjöström, C. D., Stefánsson, B. V., Langkilde, A. M., Wheeler, D. C., Heerspink, H. J. L., & DAPA-CKD Trial Committees and Investigators
- Affiliations
- Stanford Medicine (US)
- University Medical Center Groningen (NL)
- The University of Texas Southwestern Medical Center (US)
- Universitat de València (ES)
- Nanfang Hospital (CN)
- University of Glasgow (GB)
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (MX)
- University of Copenhagen (DK)
- AstraZeneca (Sweden) (SE)
- The George Institute for Global Health (AU)
- Venue
- Journal of the American Society of Nephrology
- Published
- 2021-09
- Volume
- 32
- Issue
- 9
- Pages
- 2352-2361
- ISSN
- 1046-6673 (ISSN-L)
- 1533-3450
- PMC
- PMC8729835
- OpenAlex
- W3179094902
- Semantic Scholar
- b439ebf6043333f308ff8af236ea19b26629265c
- Cited by
- 201
- References
- 28
- Citations by year
- 2026: 19 · 2025: 40 · 2024: 51 · 2023: 44 · 2022: 38 · 2021: 9
- FWCI
- 24.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Repository of Digital Objects for Teaching Research and Culture (University of Valencia) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- AstraZeneca
- Steno Diabetes Center Copenhagen (SDCC 3.A Complications)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- dapagliflozin, SGLT2 inhibitors, chronic kidney disease stage 4, albuminuria, end-stage renal disease, cardiovascular events, heart failure hospitalization, all-cause mortality, estimated glomerular filtration rate decline, DAPA-CKD trial, type 2 diabetes, renal protection, cardioprotection
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Aged, Benzhydryl Compounds, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Female, Glomerular Filtration Rate, Glucosides, Humans, Male, Middle Aged, Renal Insufficiency, Chronic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
