Dapagliflozin in Patients with Chronic Kidney Disease
Open accessAbstract
Trial of dapagliflozin in chronic kidney disease with or without type 2 diabetes.
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Claims the paper makes
12 of 16 cited sources checked · 11 supported · 0 flagged · accuracy not yet measured
- Premisecitation
Prior work, the CREDENCE trial, showed kidney-protective effects of SGLT2 inhibitors in patients with type 2 diabetes and chronic kidney disease.
“The kidney-protective effects of SGLT2 inhibitors have previously been shown in patients with type 2 diabetes and chronic kidney disease in the CREDENCE trial.10”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [10] 10. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380: 2295-306. source
- Interpretationcitation
The lower risk of heart-failure hospitalization or cardiovascular death with dapagliflozin is consistent with the DECLARE-TIMI 58 and DAPA-HF trials.
“The lower risk of hospitalization for heart failure or death from cardiovascular causes in the dapagliflozin group than in the placebo group is consistent with the results of two previous trials of dapagliflozin, the DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) and DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [9] 9. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular out- comes in type 2 diabetes. N Engl J Med 2019; 380: 347-57. source
- cites [18] 18. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019; 381: 1995-2008. source
- Premisecitation
In the CREDENCE trial, long-term canagliflozin protected against renal and cardiovascular events among patients with type 2 diabetes and chronic kidney disease.
“The CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial showed that long-term administration of canagliflozin conferred renal and cardiovascular protection in patients with type 2 diabetes with chronic kidney disease.10”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [10] 10. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380: 2295-306. source
- Findingcitation
As in other SGLT2 inhibitor trials, there was an initial dip in estimated GFR followed by stabilization of kidney-function decline.
“As in other trials of SGLT2 inhibitors, there was an initial dip in the estimated GFR, followed by a stabilization of kidney-function decline.7,8,10”
Quote in the paperNot a substantial claim3 of 3 sources checked- cites [7] 7. Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kid- ney disease in type 2 diabetes. N Engl J Med 2016; 375: 323-34. source
- cites [8] 8. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377: 644-57. source
The Renal Outcomes section reports fewer sustained 40% eGFR reductions with canagliflozin than with placebo, supporting a general kidney-protective effect. It does not report an initial eGFR dip followed by stabilization of the rate of decline; searches for those terms and for longitudinal eGFR changes found no such passage in our copy. Page numbers were not available for these passages. (LLM, conf=0.78)
Experimental — accuracy not yet measured - cites [10] 10. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380: 2295-306. source
- Premisecitation
Clinical trials of other SGLT2 inhibitors have shown similar results.
“Clinical trials of other SGLT2 inhibitors have shown similar results.8,10,19”
Quote in the paperNot a substantial claim3 of 3 sources checked- cites [8] 8. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377: 644-57. source
- cites [10] 10. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380: 2295-306. source
- cites [19] 19. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373: 2117-28. source
- Findingown data
Dapagliflozin lowered the risk of reaching an eGFR below 15 ml/min/1.73 m2 versus placebo (HR 0.67, 95% CI 0.51-0.88).
“Estimated GFR of <15 ml/min/1.73m 2 84/2152 (3.9) 1.9 120/2152 (5.6) 2.8 0.67 (0.51-0.88)NA”
Quote in the paperSubstantial claim - Findingown data
Dapagliflozin lowered the risk of the composite of cardiovascular death or heart-failure hospitalization versus placebo (HR 0.71, 95% CI 0.55-0.92, P=0.009).
“Composite of death from cardiovascular causes or hospitalization for heart failure 100/2152 (4.6) 2.2 138/2152 (6.4) 3.0 0.71 (0.55-0.92) 0.009”
Quote in the paperSubstantial claim - Findingown data
Dapagliflozin lowered the risk of a sustained eGFR decline of at least 50% versus placebo (HR 0.53, 95% CI 0.42-0.67).
“Decline in estimated GFR of ≥50% 112/2152 (5.2) 2.6 201/2152 (9.3) 4.8 0.53 (0.42-0.67)NA”
Quote in the paperSubstantial claim - Findingown data
The number needed to treat to avert one primary outcome event during the trial was 19 (95% CI, 15 to 27).
“The number of participants who needed to be treated during the trial period to prevent one primary outcome event was 19 (95% CI, 15 to 27).”
Quote in the paperSubstantial claim - Findingown data
Death from any cause occurred in 101 dapagliflozin recipients (4.7%) and 146 placebo recipients (6.8%), with a hazard ratio of 0.69 (95% CI, 0.53 to 0.88; P=0.004).
“Death occurred in 101 participants (4.7%) in the dapagliflozin group and 146 participants (6.8%) in the placebo group (hazard ratio, 0.69; 95% CI, 0.53 to 0.88; P = 0.004).”
Quote in the paperSubstantial claim - Findingown data
Dapagliflozin lowered the risk of the kidney composite (sustained eGFR decline of at least 50%, end-stage kidney disease, or renal death) versus placebo (HR 0.56, 95% CI 0.45-0.68, P<0.001).
“Composite of decline in estimated GFR of ≥50%, end-stage kidney disease, or death from renal causes 142/2152 (6.6) 3.3 243/2152 (11.3) 5.8 0.56 (0.45-0.68) <0.001”
- Also stated in: § Efficacy Outcomes · plain
“The hazard ratio for the kidney composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was 0.56 (95% CI, 0.45 to 0.68; P<0.001) (Table 2 and Fig. 1B).”
Quote in the paperSubstantial claim - Also stated in: § Efficacy Outcomes · plain
- Findingown data
Dapagliflozin lowered the risk of the composite of long-term dialysis or kidney transplantation versus placebo (HR 0.66, 95% CI 0.49-0.90).
“For the composite of long-term dialysis or kidney transplantation, there were 69 outcome events in the dapagliflozin group and 100 outcome events in the placebo group (hazard ratio, 0.66; 95% CI, 0.49 to 0.90).”
Quote in the paperSubstantial claim - Findingown data
During the first two weeks, dapagliflozin produced a larger reduction in estimated GFR than placebo (−3.97 vs −0.82 ml/min/1.73 m2).
“During the first 2 weeks, there was a greater reduction in the estimated GFR in the dapagliflozin group than in the placebo group (-3.97±0.15 vs. -0.82±0.15ml per minute per 1.73 m 2 ).”
Quote in the paperNot a substantial claim - Findingnone given
The known safety profile of dapagliflozin was confirmed in the trial.
“The known safety profile of dapagliflozin was confirmed.”
Quote in the paperNot a substantial claim - Findingown data
Dapagliflozin slowed the annual decline in estimated GFR versus placebo; the between-group difference in slope from baseline to 30 months was 0.93 ml/min/1.73 m2 per year (95% CI 0.61-1.25).
“The least-squares mean (±SE) estimated GFR slopes from baseline to 30 months in the dapagliflozin and placebo groups were -2.86±0.11and -3.79±0.11ml per minute per 1.73 m 2 per year, respectively, resulting in a between-group difference of 0.93 ml per minute per 1.73 m 2 per year (95% CI, 0.61 to 1.25) (Fig. 3).”
Quote in the paperSubstantial claim - Findingown data
Each secondary outcome occurred less often in the dapagliflozin group than in the placebo group.
“The incidence of each secondary outcome was lower in the dapagliflozin group than in the placebo group (Table 2).”
Quote in the paperSubstantial claim - Findingown data
In participants without type 2 diabetes, dapagliflozin lowered the risk of the primary composite outcome versus placebo (HR 0.50, 95% CI 0.35-0.72).
“pared with 0.50 (95% CI, 0.35 to 0.72) in participants without type 2 diabetes.”
Quote in the paperSubstantial claim - Findingown data
Dapagliflozin lowered the risk of long-term dialysis versus placebo (HR 0.66, 95% CI 0.48-0.90).
“Long-term dialysis † 68/2152 (3.2) 1.5 99/2152 (4.6) 2.2 0.66 (0.48-0.90)NA”
Quote in the paperSubstantial claim - Findingown data
For the cardiovascular composite (cardiovascular death or heart-failure hospitalization), the hazard ratio was 0.71 (95% CI, 0.55 to 0.92; P=0.009).
“and the hazard ratio for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI, 0.55 to 0.92; P = 0.009).”
Quote in the paperSubstantial claim - Findingown data
Dapagliflozin lowered the risk of death from any cause versus placebo (HR 0.69, 95% CI 0.53-0.88, P=0.004).
“Death from any cause 101/2152 (4.7) 2.2 146/2152 (6.8) 3.1 0.69 (0.53-0.88) 0.004”
- Also stated in: § Efficacy Outcomes · plain
“There were 101 deaths (4.7%) from any cause in the dapagliflozin group and 146 (6.8%) in the placebo group (hazard ratio, 0.69; 95% CI, 0.53 to 0.88; P = 0.004) (Table 2 and Fig. 1D).”
Quote in the paperSubstantial claim - Also stated in: § Efficacy Outcomes · plain
- Findingown data
Adverse events and serious adverse events occurred with similar overall frequency in the dapagliflozin and placebo groups.
“The incidences of adverse events and serious adverse events were similar overall in the dapagliflozin and placebo groups (Table 2).”
Quote in the paperSubstantial claim - Findingown data
There were 197 primary composite events among 2152 dapagliflozin recipients (9.2%) and 312 among 2152 placebo recipients (14.5%).
“Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001; number needed to treat to prevent one primary outcome event, 19 [95% CI, 15 to 27]).”
- Also stated in: § Efficacy Outcomes · plain
“The primary composite outcome of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes occurred in 197 participants (9.2%) in the dapagliflozin group and 312 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001) (Table 2 and Fig. 1A).”
Quote in the paperSubstantial claim - Also stated in: § Efficacy Outcomes · plain
- Findingown data
In CKD patients, dapagliflozin lowered the risk of the primary composite endpoint (a sustained eGFR drop of at least 50%, end-stage kidney disease, or renal or cardiovascular death) versus placebo (HR 0.61, 95% CI 0.51-0.72, P<0.001).
“Primary composite outcome 197/2152 (9.2) 4.6 312/2152 (14.5) 7.5 0.61 (0.51-0.72) <0.001”
- Also stated in: § Discussion · plain
“We found that participants with chronic kidney disease, with or without type 2 diabetes, who were randomly assigned to receive dapagliflozin had a lower risk of the primary composite outcome of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes than participants who were assigned to receive placebo.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
For the kidney composite (confirmed estimated GFR drop of 50% or more, end-stage kidney disease, or renal death), the hazard ratio was 0.56 (95% CI, 0.45 to 0.68; P<0.001).
“The hazard ratio for the composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was 0.56 (95% CI, 0.45 to 0.68; P<0.001)”
Quote in the paperSubstantial claim - Findingown data
Dapagliflozin lowered the risk of end-stage kidney disease versus placebo (HR 0.64, 95% CI 0.50-0.82).
“End-stage kidney disease 109/2152 (5.1) 2.5 161/2152 (7.5) 3.8 0.64 (0.50-0.82)NA”
Quote in the paperSubstantial claim - Findingown data
In adults with chronic kidney disease and an estimated glomerular filtration rate between 25 and 75 ml per minute per 1.73 m2 and a urinary albumin-to-creatinine ratio of 200 to 5000, dapagliflozin 10 mg once daily, compared with placebo, lowered the risk of the primary composite endpoint (confirmed drop in estimated GFR by 50% or more, end-stage kidney disease, or death from renal or心血管 causes) (
“Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001; number needed to treat to prevent one primary outcome event, 19 [95% CI, 15 to 27]).”
- Also stated in: § Efficacy Outcomes · plain
“The primary composite outcome of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes occurred in 197 participants (9.2%) in the dapagliflozin group and 312 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001) (Table 2 and Fig. 1A).”
- Also stated in: § Abstract · plain
“Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo.”
Quote in the paperSubstantial claim - Also stated in: § Efficacy Outcomes · plain
- Findingown data
For every component of the primary composite, event rates were lower with dapagliflozin.
“The event rates for all components of the composite outcome favored dapagliflozin (Table 2).”
Quote in the paperNot a substantial claim - Study design and conductreasoning
Type I error was controlled at a two-sided 0.05 level using a closed testing procedure with a prespecified hierarchy of primary and secondary outcomes.
“A closed testing procedure that included a prespecified hierarchical order of the primary and secondary outcomes was used to ensure control of type I error at a two-sided 0.05 level.”
Quote in the paperSubstantial claim - Interpretationreasoning
The same hemodynamic action might protect kidney function in patients whose kidney disease has causes other than type 2 diabetes.
“This favorable hemodynamic effect may also preserve kidney function in persons with kidney diseases due to causes other than type 2 diabetes.”
Quote in the paperSubstantial claim - Study design and conductown data
The two groups were balanced at baseline with respect to characteristics and medications for type 2 diabetes and kidney disease.
“The baseline characteristics, including medications for type 2 diabetes and kidney disease, were balanced between the dapagliflozin and placebo groups (Table 1).”
Quote in the paperSubstantial claim - Study design and conductown data
Hazard ratios and 95% confidence intervals came from a Cox proportional-hazards model that was stratified by the randomization factors and adjusted for baseline estimated GFR.
“A Cox proportional-hazards regression model that was stratified according to the factors used at randomization (type 2 diabetes and urinary albumin-to-creatinine ratio) and that was adjusted for the baseline estimated GFR was used to estimate the hazard ratio and 95% confidence intervals for dapagliflozin as compared with placebo for the primary and secondary outcomes.”
Quote in the paperSubstantial claim - Interpretationown data
Dapagliflozin had an acceptable safety profile in this population, which included participants with estimated GFR as low as 25 ml/min/1.73 m2.
“Dapagliflozin had an acceptable safety profile in this population, which included participants with an estimated GFR as low as 25 ml per minute per 1.73 m 2 .”
Quote in the paperSubstantial claim- Rests on an assumption: The early fall in estimated GFR is due to beneficial hemodynamic effects in the glomerulus.
- Study design and conductnone given
The trial was stopped on the recommendation of the independent data monitoring committee.
“First, the trial was stopped on the basis of a recommendation from the independent data monitoring committee.”
Quote in the paperNot a substantial claim - Interpretationown data
The present trial confirmed the beneficial safety profile of dapagliflozin.
“Overall, the present trial confirmed the beneficial safety profile of dapagliflozin.”
Quote in the paperSubstantial claim- Rests on an assumption: The early fall in estimated GFR is due to beneficial hemodynamic effects in the glomerulus.
- Interpretationreasoning
The strong internal and external validity of the treatment effect suggests that early stopping is unlikely to have had a major influence on the findings.
“However, the strong internal and external validity of the treatment effect suggests that this limitation is unlikely to have had a major influence on the findings.”
Quote in the paperSubstantial claim - Study design and conductreasoning
Early stopping may have reduced the power of some secondary outcomes.
“This may have reduced the power of some secondary outcomes.”
Quote in the paperNot a substantial claim - Interpretationown data
The present trial showed that CKD patients receiving dapagliflozin had a significantly lower risk of the composite outcome than those receiving placebo, independent of type 2 diabetes status.
“The present trial showed that persons with chronic kidney disease who received dapagliflozin had a significantly lower risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes than those who received placebo, independent of the presence or absence of type 2 diabetes.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 15
- May combine two claims. 16
- The quote only partly states this claim. 1
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn the CREDENCE trial and most earlier cardiovascular outcome trials of SGLT2 inhibitors, the lower inclusion cutoff for estimated GFR was 30 ml/min/1.73 m2.
“In that trial, as in most previous cardiovascular outcome trials of SGLT2 inhibitors, the lower estimated GFR cutoff for inclusion was 30 ml per minute per 1.73 m 2 .16”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [16] 16. Neuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 dia- betes: a systematic review and meta-analy- sis. Lancet Diabetes Endocrinol 2019; 7: 845-54. source
May combine two claims.
Study design and conductown dataThe trial did not collect estimated GFR values after completion and cannot determine whether the initial dip in estimated GFR is reversible after dapagliflozin discontinuation.
“We did not collect estimated GFR values after the completion of the trial and are unable to ascertain whether the initial dip in the estimated GFR is reversible after the discontinuation of dapagliflozin, as observed in other dapagliflozin studies.20”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [20] 20. Pollock C, Stefánsson B, Reyner D, et al. Albuminuria-lowering effect of dapa- gliflozin alone and in combination with saxagliptin and effect of dapagliflozin and saxagliptin on glycaemic control in patients with type 2 diabetes and chronic kidney disease (DELIGHT): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 2019; 7: 429- 41. source
The quote only partly states this claim.
Findingown dataDapagliflozin's effect on the primary endpoint was broadly consistent across prespecified subgroups, including among those with and without type 2 diabetes.
“The effects of dapagliflozin were similar in participants with type 2 diabetes and in those without type 2 diabetes.”
- Also stated in: § Efficacy Outcomes · hedged
“The effect of dapagliflozin on the primary outcome was generally consistent across prespecified subgroups (Fig. 2).”
Quote in the paperSubstantial claim- Also stated in: § Efficacy Outcomes · hedged
May combine two claims.
Findingown dataDiabetic ketoacidosis occurred in no dapagliflozin recipients and in two placebo recipients.
“Diabetic ketoacidosis was not reported in any participants who received dapagliflozin and in two participants who received placebo.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn participants without type 2 diabetes, neither diabetic ketoacidosis nor severe hypoglycemia was observed.
“Neither diabetic ketoacidosis nor severe hypoglycemia was observed in participants without type 2 diabetes.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataFollow-up lasted a median of 2.4 years (interquartile range, 2.0 to 2.7).
“At the conclusion of the trial, the median follow-up was 2.4 years (interquartile range, 2.0 to 2.7).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataOne confirmed case of Fournier's gangrene occurred in the placebo group and none in the dapagliflozin group.
“There was one confirmed case of Fournier's gangrene in the placebo group and none in the dapagliflozin group.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
Findingown dataCiting clear efficacy and 408 primary outcome events, the independent data monitoring committee advised that the trial be stopped.
“After a regular review meeting on March 26, 2020, the independent data monitoring committee recommended to the two coprincipal investigators (the first and last authors) that the trial be discontinued because of clear efficacy, on the basis of 408 primary outcome events.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe present trial studied an SGLT2 inhibitor in CKD patients, 32.5% of whom did not have type 2 diabetes and 14.5% of whom had estimated GFR below 30 ml/min/1.73 m2.
“In contrast to the CREDENCE trial, the present trial examined the effects of an SGLT2 inhibitor in patients with chronic kidney disease of whom 32.5% did not have type 2 diabetes and 14.5% had an estimated GFR below 30 ml per minute per 1.73 m 2 .”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAfter the first two weeks, the annual change in mean estimated GFR was smaller with dapagliflozin than placebo (−1.67 vs −3.59 ml/min/1.73 m2), with a between-group difference of 1.92 ml/min/1.73 m2 per year (95% CI 1.61-2.24).
“Thereafter, the annual change in the mean estimated GFR was smaller with dapagliflozin than with placebo (-1.67±0.11and -3.59±0.11ml per minute per 1.73 m 2 , respectively), for a between-group difference of 1.92 ml per minute per 1.73 m 2 per year (95% CI, 1.61 to 2.24).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataDapagliflozin recipients also had a lower risk of cardiovascular death or heart-failure hospitalization and longer survival.
“In addition, those who received dapagliflozin had a lower risk of death from cardiovascular causes or hospitalization for heart failure and had longer survival.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductown dataPower calculations indicated that 681 primary events were required to detect a 22% relative risk reduction (hazard ratio 0.78) with 90% power at a two-sided alpha of 0.05, assuming a 7.5% yearly placebo event rate.
“We estimated that 681 primary outcome events would be needed to detect a 22% lower relative risk in the dapagliflozin group than in the placebo group (hazard ratio of 0.78), with 90% power using a two-sided alpha level of 0.05 and assuming an annual event rate for the primary outcome of 7.5% in the placebo group.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationBefore this trial, only ACE inhibitors and angiotensin-receptor blockers had been shown to slow kidney function decline, but most supporting evidence came from patients with type 2 diabetes.
“Until recently, the only classes of medication that have been shown to slow a decline in kidney function were angiotensin-convertingenzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs); however, most of the evidence was generated in patients with type 2 diabetes.[3][4][5][6]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3][4][5][6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenThe first and last authors attest to the data's completeness and accuracy and to the trial's adherence to its protocol.
“The first and last authors vouch for the completeness and accuracy of the data and for the fidelity of the trial to the protocol.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Interpretationown dataThe present trial's findings confirm the high mortality among patients with impaired kidney function.
“The findings from the present trial confirm the high mortality among patients with impaired kidney function.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataAll participants and trial staff, apart from the independent data monitoring committee, remained blinded to group assignments.
“Participants and all trial personnel (except the members of the independent data monitoring committee) were unaware of the trial-group assignments.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationIn large trials of patients with type 2 diabetes, SGLT2 inhibitors reduced glycated hemoglobin and improved kidney and cardiovascular outcomes.
“Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease glycated hemoglobin levels and have shown favorable effects on kidney and cardiovascular outcomes in large clinical trials involving patients with type 2 diabetes.[7][8][9]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7][8][9]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Study design and conductown dataBy the end, 4289 participants (99.7%) had completed the trial; 11 (0.3%) withdrew consent, and vital status was missing for only 5 (0.1%).
“In all, 4289 participants (99.7%) completed the trial (i.e., were alive with follow-up data available at the trial completion visit or had died during follow-up).A total of 11 participants (0.3%) withdrew consent, and vital status was ascertained for all but 5 participants (0.1%).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataAn independent data monitoring committee monitored participant safety.
“The safety of the participants was overseen by an independent data monitoring committee.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenPrimary efficacy was analyzed in the intention-to-treat population.
“The primary efficacy analysis was based on the intention-to-treat population”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataTrial-group assignments were determined through an interactive voice-response or Web-response system.
“Investigators used an interactive voice-response or Web-response system to determine trial-group assignments.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataA blinded independent committee adjudicated all primary and secondary outcomes, except some estimated GFR outcomes obtained from central laboratory measurements.
“An independent committee whose members were unaware of the trial-group assignments adjudicated all primary and secondary outcomes, except for a sustained decline in the estimated GFR of at least 50% and a sustained estimated GFR of less than 15 ml per minute per 1.73 m 2 , which were ascertained from central laboratory measurements.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataStratification factors at randomization were type 2 diabetes status and urinary albumin-to-creatinine ratio (≤1000 or >1000).
“Randomization was stratified according to the diagnosis of type 2 diabetes (yes or no) and the urinary albumin-to-creatinine ratio (≤1000 or >1000).”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataThe kidney-protective effects of SGLT2 inhibitors extend to the broader CKD population without type 2 diabetes, for whom ACE inhibitors are the only pharmacologic treatments shown to prevent kidney failure.
“Our trial confirms that the kidneyprotective effects of SGLT2 inhibitors extend to the broader population of persons with chronic kidney disease without type 2 diabetes, for whom ACE inhibitors are the only pharmacologic treatments that have been shown to prevent kidney failure.3,4”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [3] 3. Ruggenenti P, Perna A, Gherardi G, et al. Renoprotective properties of ACE-inhi- bition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet 1999; 354: 359-64. source
- cites [4] 4. Hou FF, Zhang X, Zhang GH, et al. Efficacy and safety of benazepril for ad- vanced chronic renal insufficiency. N Engl J Med 2006; 354: 131-40. source
May combine two claims.
Study design and conductown dataThe trial was randomized, double-blind, placebo-controlled, and multicenter.
“Our trial was a randomized, double-blind, placebo-controlled, multicenter clinical trial; details regarding the trial design and baseline characteristics of the participants have been published previously.14,15”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAn independent academic group at the University Medical Center Groningen repeated the sponsor's analyses.
“The analyses that were conducted by the sponsor were replicated by an independent academic group at the University Medical Center Groningen.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductnone givenThe dapagliflozin and placebo tablets had identical packaging, appearance, labeling, and administration schedules.
“Dapagliflozin and placebo were packaged identically, with uniform tablet appearance, labeling, and administration schedules.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataNon-death discontinuation occurred in 274 dapagliflozin recipients and 309 placebo recipients (12.7% and 14.4%, respectively).
“Dapagliflozin was discontinued for reasons other than death in 274 participants, and placebo was discontinued in 309 participants (12.7% and 14.4%, respectively).”
Quote in the paperNot a substantial claim
The paper relies on this without support.
At the time of the study, it was unknown how dapagliflozin would affect people with chronic kidney disease, whether or not they had type 2 diabetes.
“The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known.”
The paper relies on this without support.
The early fall in estimated GFR is due to beneficial hemodynamic effects in the glomerulus.
“This dip in the estimated GFR reflects favorable hemodynamic changes in the glomerulus.”
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?
In the DAPA-CKD trial, among 4304 participants with chronic kidney disease, dapagliflozin reduced the primary composite outcome of a sustained decline in eGFR of at least 50%, end-stage kidney disease, or death from renal or CV causes by 44% (HR, 0.56 [95% CI 0.45-0.68]; P < 0.001).
“Among 4304 participants, with or without type 2 diabetes, with an eGFR between 25 and 75 mL/min/1.73 m2 and proteinuria (a urinary albumin-to-creatinine ratio of 22.6-565.6 mg/mmol) who were randomly assigned to dapagliflozin 10 mg daily or placebo, the primary composite outcome of a sustained decline in eGFR of at least 50%, end-stage kidney disease, or death from renal or CV causes was reduced”
From CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction (2021) · cites this paper as [50]
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe DAPA-CKD trial of dapagliflozin required participants to have a urinary ACR of 200 mg/g and an eGFR of 25 to 75 ml per minute per 1.73 m2, and included 1398 participants without diabetes and 624 participants with an eGFR below 30 ml per minute per 1.73 m2.
“The DAPA-CKD trial of dapagliflozin required participants to have a urinary ACR of 200 mg/g and an eGFR of 25 to 75 ml per minute per 1.73 m2. It included 1398 participants without diabetes and 624 participants with an eGFR below 30 ml per minute per 1.73 m2.7”
From Empagliflozin in Patients with Chronic Kidney Disease (2023) · cites this paper as [7]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIn DAPA-CKD, all-cause mortality was decreased in the dapagliflozin group compared with the placebo group (P < 0.004).
“Finally, all-cause mortality was decreased in the dapagliflozin group compared with the placebo group (P < 0.004).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [114]
The Efficacy Outcomes section reports fewer deaths from any cause with dapagliflozin than with placebo (101 versus 146), supporting the mortality comparison. It reports P = 0.004, however, not P < 0.004 as claimed. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSGLT2 inhibitors and finerenone reduce albuminuria in clinical trials of advanced diabetic kidney disease.
“SGLT2 inhibitors and finerenone, a nonsteroidal mineralocorticoid receptor antagonist, also reduce albuminuria in clinical trials of advanced diabetic kidney disease (471-473).”
From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [472]
The Participants and Discussion sections describe a clinical trial of dapagliflozin, an SGLT2 inhibitor, in people with chronic kidney disease, including those with type 2 diabetes. The reported benefit concerns kidney and cardiovascular outcomes; the paper does not report that dapagliflozin reduced albuminuria, and it does not address finerenone. (LLM, conf=0.81)
Experimental — accuracy not yet measuredIn the CREDENCE and DAPA-CKD trials, kidney outcomes were the primary outcome evaluated.
“Of note, in the CREDENCE and DAPA-CKD trials, kidney outcomes were the primary outcome evaluated.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [94]
The Efficacy Outcomes section identifies DAPA-CKD’s primary outcome as a composite of kidney outcomes and death from renal or cardiovascular causes. The Discussion says CREDENCE showed kidney-protective effects, but does not state that kidney outcomes were its primary outcome. Thus, the cited paper supports the DAPA-CKD portion but not the specific claim about CREDENCE’s primary outcome. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Direct evidence for safety and benefit of SGLT2i in eGFR 20-29 is provided by the DAPA-CKD, SCORED, EMPEROR-Reduced, and EMPEROR-Preserved trials, which enrolled such participants by design.
“Direct evidence is provided by the DAPA-CKD, SCORED, EMPEROR-Reduced, and EMPEROR-Preserved trials, which enrolled such participants by design.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [94]
The Methods report that DAPA-CKD enrolled participants with eGFR 25–75, and the Discussion says 14.5% had eGFR below 30; it also reports an overall benefit and acceptable safety profile. Thus this paper provides evidence for enrolled patients in the 25–29 range, but it does not establish benefit and safety specifically across the full 20–29 range, because patients with eGFR 20–24 were not enrolled. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSGLT2i have been studied among patients without T2D who have CKD in the DAPA-CKD trial (and the soon-to-be-published EMPA-KIDNEY trial) or who have heart failure (in the DAPA-HF, EMPEROR-Reduced, and EMPEROR-Preserved trials) and did not confer any increased risk of severe hypoglycemia or diabetic ketoacidosis among individuals without T2D.
“However, notably, SGLT2i have been studied among patients without T2D who have CKD in the DAPA-CKD trial (and the soonto-be-published EMPA-KIDNEY trial) or who have heart failure (in the DAPA-HF, EMPEROR-Reduced, and EMPEROR-Preserved trials) and did not confer any increased risk of severe hypoglycemia or diabetic ketoacidosis among individuals without T2D.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [94]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredProtocols of multiple RCTs, including CREDENCE and DAPA-CKD, specified continuation of study drug (active or placebo) even when observed eGFR dropped below the eligibility threshold specified for initiation.
“Protocols of multiple RCTs, including CREDENCE and DAPA-CKD, speci fi ed continuation of study drug (active or placebo) even when observed eGFR dropped below the eligibility threshold speci fi ed for initiation.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [94]
The Participants section (page unavailable) gives DAPA-CKD’s lower eligibility threshold as an eGFR of 25, and Trial Procedures (page unavailable) says dapagliflozin or placebo was to be discontinued for pregnancy or diabetic ketoacidosis. Our copy does not say that the protocol specified continued treatment after eGFR fell below 25, or establish that CREDENCE specified the same practice. (LLM, conf=0.76)
Experimental — accuracy not yet measuredPrevious studies assessing SGLT-2 inhibitors in patients with CKD and type 2 diabetes, such as CREDENCE or DAPA-CKD, included patient populations representing a substantially smaller part of the CKD spectrum than the FIDELITY analysis.
“Previous studies assessing SGLT-2 inhibitors in patients with CKD and type 2 diabetes, such as CREDENCE or DAPA-CKD, included patient populations representing a substantially smaller part of the CKD spectrum than the FIDELITY analysis.”
From Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis (2022) · cites this paper as [27]
The Participants section describes DAPA-CKD as an SGLT2-inhibitor trial with defined kidney-function and albuminuria eligibility ranges; the Discussion also identifies CREDENCE as a trial in patients with type 2 diabetes and CKD. The paper does not compare either trial’s coverage of the CKD spectrum with the FIDELITY analysis, so it does not establish the claimed substantially smaller coverage. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn DAPA-CKD, all-cause mortality was decreased in the dapagliflozin group compared with placebo (P < 0.004).
“Finally, allcause mortality was decreased in the dapagliflozin group compared with the placebo group (P < 0.004).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [127]
The Efficacy Outcomes section reports fewer deaths from any cause with dapagliflozin than with placebo (101 versus 146). It gives P = 0.004, not P < 0.004; the claimed strict inequality is not supported. (LLM, conf=0.92)
Experimental — accuracy not yet measuredClinical studies have demonstrated the cardiovascular and kidney benefits of SGLT2i and GLP-1RA, especially the CREDENCE and DAPA-CKD trials, which were specially designed to focus on patients with CKD.
“Clinical studies have demonstrated the cardiovascular and kidney benefits of SGLT2i and GLP-1RA, especially the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) and the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trials, which were specially designed to focus on patients with CKD.6,8”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [6]
The Abstract (p. 1437) identifies DAPA-CKD as a trial designed for patients with chronic kidney disease and reports kidney and cardiovascular benefits of the SGLT2 inhibitor dapagliflozin. The Discussion also reports kidney-protective effects from CREDENCE. This paper does not address GLP-1 receptor agonist benefits, so it does not support that part of the sentence. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCREDENCE and DAPA-CKD demonstrated significant benefit for composite outcomes including substantial eGFR decline, kidney failure, and mortality.
“To date, two clinical trials with primary kidney disease outcomes using canagliflozin and dapagliflozin (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation [CREDENCE] and Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease [DAPA-CKD]) demonstrated significant benefit for composite outcomes including end points of substantial eGFR decl”
From Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) (2022) · cites this paper as [54]
The Efficacy Outcomes section reports a significant DAPA-CKD benefit for a composite of substantial eGFR decline, end-stage kidney disease, and renal or cardiovascular death (hazard ratio 0.61; P<0.001). The Discussion says CREDENCE showed kidney-protective effects, but this copy does not specify CREDENCE’s composite endpoints or their statistical significance. (LLM, conf=0.84)
Experimental — accuracy not yet measuredDAPA-CKD provided clear evidence of efficacy and safety for dapagliflozin in patients with eGFR ≥25 mL/min/1.73 m2 and ACR ≥200 mg/g.
“including the DAPA-CKD trial (which provided clear evidence of efficacy and safety for dapagliflozin in patients with eGFR ≥25 mL/min/1.73 m2 and ACR ≥200 mg/g)”
From Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) (2022) · cites this paper as [54]
The Abstract (p. 1437) reports that DAPA-CKD enrolled patients with eGFR of 25–75 mL/min/1.73 m² and urinary albumin-to-creatinine ratio of 200–5000 mg/g, and found a lower primary-outcome risk with dapagliflozin. The Discussion reports an acceptable safety profile. The citing sentence omits both upper eligibility limits, so its efficacy-and-safety claim reaches patients outside the studied ranges. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn DAPA-CKD, all-cause mortality was significantly reduced (HR, 0.69; [95% CI 0.53-0.88]; P = 0.004) and the safety profile of dapagliflozin was confirmed.
“All-cause mortality was also significantly reduced (HR, 0.69; [95% CI 0.53-0.88]; P = 0.004) and the safety profile of dapagliflozin was confirmed in this group.”
From CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction (2021) · cites this paper as [50]
In DAPA-CKD, the hazard ratio for the composite of death from CV causes or HHF was 0.71 ([95% CI 0.55-0.92]; P = 0.009).
“The hazard ratio for the composite of death from CV causes or HHF was 0.71 ([95% CI 0.55-0.92]; P = 0.009).”
From CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction (2021) · cites this paper as [50]
In patients with diabetic kidney disease and increased albuminuria, large placebo-controlled trials have shown that RAS inhibitors, SGLT2 inhibitors, and finerenone each reduced the risk of progression to kidney failure.
“In patients with diabetic kidney disease with increased levels of albuminuria, large placebo-controlled trials have shown that renin-angiotensin system (RAS) inhibitors,3–5 sodium-glucose cotransporter 2 (SGLT2) inhibitors,6,7 and the non-steroidal mineralocorticoid receptor antagonist finerenone8,9 all reduced the risk of progression to kidney failure.”
From Empagliflozin in Patients with Chronic Kidney Disease (2023) · cites this paper as [7]
A prespecified subgroup analysis from a trial of dapagliflozin in patients with chronic kidney disease and urinary ACR of at least 200 mg/g found that kidney benefits extended to patients without diabetes.
“A prespecified subgroup analysis from a trial of the SGLT2 inhibitor dapagliflozin in patients with CKD and a urinary ACR of at least 200 mg/g, found that kidney benefits extended to patients without diabetes”
From Empagliflozin in Patients with Chronic Kidney Disease (2023) · cites this paper as [7]
There was limited information from patients with an estimated GFR below 30 ml per minute per 1.73 m2 or on how kidney benefits might vary among the wider range of patients with chronic kidney disease.
“but there was limited information from patients with an estimated GFR (eGFR) below 30 ml per minute per 1.73 m2 or on how these benefits might vary among the wider range of patients with CKD.7,12,13”
From Empagliflozin in Patients with Chronic Kidney Disease (2023) · cites this paper as [7]
The effect of SGLT2 inhibition on kidney disease progression or cardiovascular death in EMPA-KIDNEY is quantitatively similar to that seen in two other large placebo-controlled trials in CKD populations.
“The effect of SGLT2 inhibition on kidney disease progression or cardiovascular death seen in the present trial is quantitatively similar to that seen in two other large placebo-controlled trials in CKD populations.6,7”
From Empagliflozin in Patients with Chronic Kidney Disease (2023) · cites this paper as [7]
In DAPA-CKD, the HR for the kidney composite of a sustained decline in eGFR of ≥50%, ESKD, or death from renal causes was 0.56 (95% CI 0.45-0.68; P < 0.001).
“The HR for the kidney composite of a sustained decline in eGFR of $50%, ESKD, or death from renal causes was 0.56 (95% CI 0.45-0.68;P < 0.001).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [114]
In DAPA-CKD, the HR for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI 0.55-0.92; P = 0.009).
“The HR for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI 0.55-0.92;P = 0.009).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [114]
In DAPA-CKD, there was a significant benefit by dapagliflozin for the primary end point (HR 0.61 [95% CI 0.51-0.72]; P < 0.001).
“There was a significant benefit by dapagliflozin for the primary end point (hazard ratio [HR] 0.61 [95% CI 0.51-0.72];P < 0.001) (114).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [114]
SGLT-2 inhibitors have benefits in patients with heart failure and chronic kidney disease, regardless of the presence of diabetes.
“Clinical trials, such as EMPEROR-REDUCED (empagliflozin) and DAPA-CKD (dapagliflozin), have shown that SGLT-2 inhibitors have benefits in patients with heart failure and chronic kidney disease, regardless of the presence of diabetes.38,39”
From Tirzepatide: Clinical review of the twincretin injectable (2023) · cites this paper as [38]
The DAPA-CKD and SCORED trials enrolled CKD patients with an eGFR down to as low as 25 ml/min per 1.73 m2.
“The DAPA-CKD 94 and SCORED 96 trials enrolled CKD patients with an eGFR down to as low as 25 ml/min per 1.73 m 2 .”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [94]
In DAPA-CKD, dapagliflozin reduced the risk of the secondary cardiovascular outcome of death from cardiovascular cause or hospitalization for heart failure by 29% (HR 0.71; 95% CI 0.55-0.92).
“dapagli fl ozin reduced the risk of the secondary cardiovascular outcome of death from cardiovascular cause or hospitalization for heart failure by 29% (HR: 0.71; 95% CI: 0.55 -0.92).”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [94]
In DAPA-CKD, findings were similar among patients with and without T2D.
“Findings were similar among patients with and without T2D.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [94]
In DAPA-CKD, over a median of 2.4 years, dapagliflozin reduced the primary kidney outcome by 39% (HR 0.61; 95% CI 0.51-0.72).
“Over a median of 2.4 years, dapagli fl ozin reduced the primary kidney outcome by 39% (HR: 0.61; 95% CI: 0.51 -0.72).”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [94]
The evidence is particularly strong for the population corresponding to the CREDENCE and DAPA-CKD studies (ACR >200-300 mg/g and eGFR >25-30 and <75-90 ml/min per 1.73 m2).
“Thus, the evidence is particularly strong for the population corresponding to the CREDENCE and DAPACKD studies (ACR > 200 -300 mg/g [ > 20 -30 mg/mmol] and eGFR > 25 -30 and < 75 -90 ml/min per 1.73 m 2 .”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [94]
In DAPA-CKD, dapagliflozin significantly reduced the primary end point (HR 0.61 [95% CI 0.51-0.72]; P < 0.001).
“There was a significant benefit by dapagliflozin for the primary end point (HR 0.61 [95% CI 0.51-0.72];P < 0.001) (127).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [127]
In DAPA-CKD, the HR for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI 0.55-0.92; P = 0.009).
“The HR for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI 0.55-0.92;P = 0.009).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [127]
In DAPA-CKD, the HR for the kidney composite of a sustained decline in eGFR of ≥50%, kidney failure, or death from kidney causes was 0.56 (95% CI 0.45-0.68; P < 0.001).
“The HR for the kidney composite of a sustained decline in eGFR of ≥50%, kidney failure, or death from kidney causes was 0.56 (95% CI 0.45-0.68;P < 0.001).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [127]
Further studies have shown renoprotective effects of dapagliflozin.
“Further studies have shown renoprotective effects of dapagliflozin (259).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [259]
Large clinical trials have shown benefits of newer glucose-lowering medications on cardiovascular and kidney outcomes in patients with CKD with type 2 diabetes.
“Large clinical trials have shown benefits of newer glucose-lowering medications on cardiovascular and kidney outcomes in patients with CKD with type 2 diabetes.5, 6, 7, 8, 9, 10, 11, 12, 13, 14”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [6]
Five large randomized clinical trials demonstrated cardiovascular benefits and kidney protective benefits of SGLT2i.
“Five large randomized clinical trials (the EMPA-REG OUTCOME, the Canagliflozin Cardiovascular Assessment Study [CANVAS], the Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58 [DECLARE–TIMI 58], CREDENCE, and DAPA-CKD) demonstrated cardiovascular benefits, and kidney protective benefits of SGLT2i.5, 6, 7, 8,11,12,34”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [6]
Significant benefits of SGLT2i were shown among the subgroup patients (aged ≥65 years) in the study of EMPAREG, CANVAS, DECLARE, and DAPA-CKD.
“However, significant benefits of SGLT2i were shown among the subgroup patients (aged greater than or equal to 65 years) in the study of EMPAREG, CANVAS, DECLARE, and DAPA-CKD.6, 7, 8,11,12,34”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [6]
The 2 clinical trials, CREDENCE and DAPA-CKD, showed that risk of UTIs with SGLT2i was similar to that with placebo.
“The 2 clinical trials, CREDENCE and DAPA-CKD, which specifically focused on patients with CKD, showed that risk of UTIs with SGLT2i was similar to that with placebo.6,8”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [6]
The Safety Outcomes and Adverse Events section says overall adverse-event incidence was similar with dapagliflozin and placebo, but it does not report urinary tract infection (UTI) risk. Table 2 lists selected adverse events without a UTI result. Searches for “urinary tract infection” and “UTI” found no passage establishing the claimed comparison for DAPA-CKD; this copy also does not report CREDENCE UTI results. (LLM, conf=0.76)
Experimental — accuracy not yet measuredSGLT2 inhibitors have been shown to reduce the risk of hospitalizations for heart failure in 8 large-scale trials, including those focused on type 2 diabetes, heart failure with reduced ejection fraction, and chronic kidney disease.
“Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the risk of hospitalizations for heart failure in 8 large-scale trials, including those that focused on type 2 diabetes, heart failure with a reduced ejection fraction, and chronic kidney disease.1–8”
From Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial (2021) · cites this paper as [8]
Treatment with dapagliflozin reduces adverse kidney events and decreases mortality among patients with chronic kidney disease (CKD).
“Treatment with dapagliflozin reduces adverse kidney events and decreases mortality among patients with chronic kidney disease (CKD).9”
From Association of race/ethnicity, gender, and socioeconomic status with sodium-glucose cotransporter 2 inhibitor use among patients with diabetes in the US (2021) · cites this paper as [9]
SGLT2 inhibitors have been studied in patients with CKD with or without T2D in three completed primary kidney outcome trials (CREDENCE, DAPA-CKD, and EMPA-KIDNEY), which showed benefit for significant reduction in primary kidney outcomes and cardiovascular outcomes.
“Furthermore, SGLT2i have been studied specifically among patients with CKD with or without T2D in 3 completed primary kidney outcome trials (CREDENCE[15], DAPA-CKD[16], and EMPA-KIDNEY[17]), which showed benefit for both a significant reduction in the primary kidney outcomes and cardiovascular outcomes [18,19].”
From Glucagon-like peptide-1 receptor agonists in diabetic kidney disease: a review of their kidney and heart protection (2023) · cites this paper as [16]
Dapagliflozin, finerenone, and empagliflozin are effective and safe in patients with eGFR ≥25 or ≥20 mL/min/1.73 m2, although safety data are lacking for initiating therapy below these thresholds.
“The DAPA-CKD and FIDELIO trials enrolled patients with eGFR ≥25 mL/min/1.73 m2 and the EMPA-KIDNEY trial enrolled patients with eGFR ≥20 mL/min/1.73 m2; results demonstrated that dapagliflozin, finerenone and empagliflozin are effective and safe in these patients, although safety data are lacking for initiating therapy below these thresholds [16,17,22].”
From Glucagon-like peptide-1 receptor agonists in diabetic kidney disease: a review of their kidney and heart protection (2023) · cites this paper as [16]
In contrast to GLP1-RA, SGLT2i have had 3 dedicated kidney outcome trials that specifically enrolled a CKD population.
“This is in contrast to SGLT2i where there have been 3 dedicated kidney outcome trials that specifically enrolled a CKD population.”
From Glucagon-like peptide-1 receptor agonists in diabetic kidney disease: a review of their kidney and heart protection (2023) · cites this paper as [16]
Large trials have shown that SGLT2 inhibitors reduce the risk of kidney disease progression in patients with type 2 diabetes and proteinuric chronic kidney disease.
“Large trials have also shown that SGLT2 inhibitors reduce the risk of kidney disease progression in patients with type 2 diabetes and proteinuric chronic kidney disease,1, 6, 7, 8”
The DAPA-CKD trial in patients with proteinuric chronic kidney disease reported just 109 kidney disease progression outcomes in patients without diabetes.
“the DAPA-CKD trial in patients with proteinuric chronic kidney disease reported just 109 kidney disease progression outcomes in patients without diabetes.1, 8, 10”
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.”
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.”
Individual trials have shown that kidney benefits translate into important reductions in the need for dialysis or kidney transplantation.
“Individual trials have shown that kidney benefits translate into important reductions in the need for dialysis or kidney transplantation”
The primary results of DAPA-CKD showed that in patients with CKD, regardless of the presence or absence of type 2 diabetes and regardless of CKD etiology, dapagliflozin significantly reduced the risk of the primary composite outcome and secondary outcomes, including all-cause mortality, compared with placebo.
“The primary results showed that in patients with CKD, regardless of the presence or absence of type 2 diabetes and regardless of CKD etiology, dapagli fl ozin signi fi cantly reduced the risk of the primary composite outcome and the secondary outcomes, including all-cause mortality, compared with placebo. 18”
From A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy (2021) · cites this paper as [18]
In individuals with or without type 2 diabetes, SGLT2 inhibitors cut the likelihood of progressing to kidney failure.
“Sodium glucose co-transporter (SGLT) 2 inhibitors reduce the risk of kidney failure in patients with and without type 2 diabetes (T2D).”
From A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors (2021) · cites this paper as Heerspink et al., 2020
Dapagliflozin had beneficial effects in CKD patients with or without type 2 diabetes.
“effects of the SGLT2 inhibitor dapagliflozin in patients with CKD with or without T2D (Heerspink et al., 2020; Wheeler et al., 2021).”
From A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors (2021) · cites this paper as Heerspink et al., 2020
The DAPA-CKD trial showed kidney benefit in chronic kidney disease patients both with and without type 2 diabetes.
“Recent findings of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial support this notion by demonstrating beneficial kidney failure both in the subgroup of patients with and without T2D (Heerspink et al., 2020).”
From A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors (2021) · cites this paper as Heerspink et al., 2020
In DAPA-CKD, dapagliflozin lowered the risk of the composite of cardiovascular death or hospitalization for heart failure (HR 0.71, 95% CI 0.55-0.92).
“or hospitalization for heart failure (HR 0.71 [95% CI 0.55 -0.92]).”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [197]
In DAPA-CKD, dapagliflozin lowered the risk of a renal composite outcome of sustained eGFR decline of at least 50%, end-stage kidney disease, or renal death (HR 0.56, 95% CI 0.45-0.68).
“as were the risks for a renal composite outcome of sustained decline in eGFR of at least 50%, endstage kidney disease, or death from renal causes (HR 0.56 [95% CI 0.45 -0.68])”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [197]
In DAPA-CKD, the effects of dapagliflozin were similar in individuals with and without type 2 diabetes.
“The effects of dapagli fl ozin therapy were similar in individuals with and without type 2 diabetes.”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [197]
In DAPA-CKD, dapagliflozin lowered the risk of the primary composite outcome of sustained eGFR decline of at least 50%, end-stage kidney disease, or renal or cardiovascular death compared with placebo (HR 0.61, 95% CI 0.51-0.72).
“The risk of the primary composite outcome was signi fi cantly lower with dapagli fl ozin therapy compared with placebo (HR 0.61 [95% CI 0.51 -0.72])”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [197]
In DAPA-CKD, over a median follow-up of 2.4 years, the primary outcome occurred in 9.2% of dapagliflozin participants and 14.5% of placebo participants.
“Over a median follow-up period of 2.4 years, a primary outcome event occurred in 9.2% of participants in the dapagli fl ozin group and 14.5% of those in the placebo group.”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [197]
Despite improvements in kidney outcomes with available pharmacotherapies, the risk of kidney failure in people with CKD and type 2 diabetes remains high.
“Despite improvements in kidney outcomes with available pharmacotherapies, the risk of kidney failure in people with CKD and T2D remains high [14,15].”
Despite the availability of established and newer pharmacotherapies to delay CKD progression in people with T2D, the risk of progression and the associated morbidity and mortality remains substantial.
“Despite the availability of established and newer pharmacotherapies to delay CKD progression in people with T2D, the risk of progression and the associated morbidity and mortality remains substantial [14,15].”
There is substantial overlap between the FLOW population and the populations studied in the dedicated kidney outcome studies with SGLT2is (CREDENCE, DAPA-CKD and EMPA-KIDNEY).
“There is substantial overlap between the FLOW population and the populations studied in the dedicated kidney outcome studies with SGLT2is (CREDENCE, DAPA-CKD and EMPA-KIDNEY) [15,30,32]”
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“SGLT2 inhibitor is recommended as first-line treatment with metformin and may also have benefits in persons with CKD and no diabetes.(67,68) Sodium-glucose cotransporter-2 (SGLT2) inhibitors should be initiated if estimated glomerular filtration rate (eGFR) 30 ml/min per 1.”
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“shown to improve clinical outcomes (mortality or progression of CKD and cardiovascular events) in CKD patients [141, 142].”
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“primary or secondary kidney disease within the previous 6 months before trial enrollment.(16,17)”
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2023 ESC Guidelines for the management of acute coronary syndromes
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“Safety outcomes from clinical trials of dapagliflozin have also shown similar incidences of adverse events in both placebo and dapagliflozin arms [58, 61].”
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Self-citationDapagliflozin in Myocardial Infarction without Diabetes or Heart Failure
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“The exact mechanism has not been fully established yet, and SGLT2 inhibitors show many additional beneficial effects which contribute to their wider use, even in non-diabetic patients [14].”
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11. Chronic Kidney Disease and Risk Management: <i>Standards of Medical Care in Diabetes—2022</i>
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Self-citation11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2023
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Sodium-Glucose Cotransporter 2 Inhibitors Mechanisms of Action: A Review
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“Clinical trials on diabetic and non-diabetic patients with chronic kidney disease (CKD) (22, 34) have demonstrated that SGLT2 inhibitors reduce albuminuria significantly.”
BackgroundInfluentialSelf-citation11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2024
ElSayed, N. A., Aleppo, G., Bannuru, R. R., Bruemmer, D., Collins, B. S., Ekhlaspour, L., Hilliard, M. E., Johnson, E. L., Khunti, K. K., Lingvay, I., et al. (2023) · Diabetes Care · doi:10.2337/dc24-s011 · Cited by 292 · see citing works
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“73 m(2).(9,12) The Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR-Reduced) and The EmpagliflozinOutcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved) trials, although not conducted exclusively in CKD popula…”
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11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Echouffo-Tcheugui, J. B., Ekhlaspour, L., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s011 · Cited by 262 · see citing works
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“Despite the availability of established and newer pharmacotherapies to delay CKD progression in people with T2D, the risk of progression and the associated morbidity and mortality remains substantial [14, 15].”
BackgroundInfluentialSelf-citationRenal Protection with SGLT2 Inhibitors: Effects in Acute and Chronic Kidney Disease
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Self-citationMapping the single-cell transcriptomic response of murine diabetic kidney disease to therapies
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Self-citationTreatment of Diabetic Kidney Disease: Current and Future
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“A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease (DAPA-CKD) study, a phase III study of dapagliflozin, reported that dapagliflozin was effective in patients with CKD, with or without type 2 diabetes mellitus [50].”
Background2021 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
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“From a safety perspective, similar to CVOTs, a higher incidence of genital mycotic infection (GMI) noted was also observed, although reassuringly, no increase in serious volume depletion, hypotension, or hypoglycemia was observed in CREDENCE or DAPA-CKD.8,46 In CREDENCE, the incidence of diabetic ketoacidosis (DKA) wa…”
BackgroundInfluentialMechanisms of podocyte injury and implications for diabetic nephropathy
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Jongs, N., Greene, T., Chertow, G. M., McMurray, J. J. V., Langkilde, A. M., Correa‐Rotter, R., Rossing, P. R., Sjöström, C. D., Stefánsson, B. V., Toto, R. D., et al. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00243-6 · Cited by 236 · see citing works
Self-citationOxidative Stress: A Culprit in the Progression of Diabetic Kidney Disease
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- Authors
- Heerspink, H. J. L., Stefánsson, B. V., Correa-Rotter, R., Chertow, G. M., Greene, T., Hou, F.-F., Mann, J. F. E., McMurray, J. J. V., Lindberg, M., Rossing, P., Sjöström, C. D., Toto, R. D., Langkilde, A.-M., & Wheeler, D. C.
- Affiliations
- University Medical Center Groningen (NL)
- From the Department Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands (H.J.L.H.); the George Institute for Global Health, Sydney (H.J.L.H., D.C.W.); Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden (B.V.S., M.L., C.D.S., A.-M.L.); the National Medical Science and Nutrition Institute Salvador Zubirán, Mexico City (R.C.-R.); the Departments of Medicine...
- University of Copenhagen (DK)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-10-08
- Volume
- 383
- Issue
- 15
- Pages
- 1436-1446
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3088173406
- Cited by
- 5,618
- References
- 20
- Citations by year
- 2026: 1014 · 2025: 987 · 2024: 978 · 2023: 967 · 2022: 824 · 2021: 743 · 2020: 94 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 412.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
- UCL Discovery (University College London) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- AstraZeneca
- 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
- chronic kidney disease, SGLT2 inhibitors, type 2 diabetes, estimated glomerular filtration rate decline, end-stage renal disease, cardiovascular mortality, heart failure hospitalization, albuminuria, renal outcomes, drug safety, body surface area dosing, albumin-creatinine ratio
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Aged, Benzhydryl Compounds, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Female, Glomerular Filtration Rate, Glucosides, Humans, Kidney Failure, Chronic, Male, Middle Aged, Regression Analysis, Renal Insufficiency, Chronic, Kaplan-Meier Estimate
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