The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index; 18 of the 31 sources its claims cite were checked for support.
SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis
Open accessAbstract
Background The effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors on kidney failure, particularly the need for dialysis or transplantation or death due to kidney disease, is uncertain. Additionally, previous studies have been underpowered to robustly assess heterogeneity of effects on kidney outcomes by different levels of estimated glomerular filtration rate (eGFR) and albuminuria. We aimed to do a systematic review and meta-analysis to assess the effects of SGLT2 inhibitors on major kidney outcomes in patients with type 2 diabetes and to determine the consistency of effect size across trials and different levels of eGFR and albuminuria. Methods We did a systematic review and meta-analysis of randomised, controlled, cardiovascular or kidney outcome trials of SGLT2 inhibitors that reported effects on major kidney outcomes in people with type 2 diabetes. We searched MEDLINE and Embase from database inception to June 14, 2019, to identify eligible trials. The primary outcome was a composite of dialysis, transplantation, or death due to kidney disease. We used random-effects models to obtain summary relative risks (RRs) with 95% CIs and random-effects meta-regression to explore effect modification by subgroups of baseline eGFR, albuminuria, and use of renin–angiotensin system (RAS) blockade. This review is registered with PROSPERO (CRD42019131774). Findings From 2085 records identified, four studies met our inclusion criteria, assessing three SGLT2 inhibitors: empagliflozin (EMPA-REG OUTCOME), canagliflozin (CANVAS Program and CREDENCE), and dapagliflozin (DECLARE–TIMI 58). From a total of 38 723 participants, 252 required dialysis or transplantation or died of kidney disease, 335 developed end-stage kidney disease, and 943 had acute kidney injury. SGLT2 inhibitors substantially reduced the risk of dialysis, transplantation, or death due to kidney disease (RR 0·67, 95% CI 0·52–0·86, p=0·0019), an effect consistent across studies ( I 2 =0%, p heterogeneity =0·53). SGLT2 inhibitors also reduced end-stage kidney disease (0·65, 0·53–0·81, p<0·0001), and acute kidney injury (0·75, 0·66–0·85, p<0·0001), with consistent benefits across studies. Although we identified some evidence that the proportional effect of SGLT2 inhibitors might attenuate with declining kidney function (p trend =0·073), there was clear, separate evidence of benefit for all eGFR subgroups, including for participants with a baseline eGFR 30–45 mL/min per 1·73 m 2 (RR 0·70, 95% CI 0·54–0·91, p=0·0080). Renoprotection was also consistent across studies irrespective of baseline albuminuria (p trend =0·66) and use of RAS blockade (p heterogeneity =0·31). Interpretation SGLT2 inhibitors reduced the risk of dialysis, transplantation, or death due to kidney disease in individuals with type 2 diabetes and provided protection against acute kidney injury. These data provide substantive evidence supporting the use of SGLT2 inhibitors to prevent major kidney outcomes in people with type 2 diabetes. Funding None.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
23 Own result · 16 Own method · 10 Own interpretation · 8 No full text of the sources · 7 Supported · 7 Partly supported · 6 No basis given · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the mechanism for the effect on kidney haemodynamics has only been studied in patients with type 1 diabetes with whole-kidney hyperfiltration and at an individual nephron level in animal models; 39”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
What the sources say
- Partly supportedcites [39] Kidokoro, 2019, Evaluation of glomerular hemodynamic function by empagliflozin in diabetic mice using in vivo imaging, Circulation sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports prior whole-kidney haemodynamic measurements in patients with type 1 diabetes, and the Conclusions describe this paper’s single-nephron findings in diabetic mice. The paper does not establish the claim’s exclusive “only been studied” limit; it also mentions an empagliflozin study in children with type 2 diabetes, though not a direct study of the mechanism. (LLM, conf=0.83)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“the only other treatment effective in slowing the progression of diabetic kidney disease”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
What the sources say
- Supportedcites [38] Tuttle, 2017, Back to the future: glomerular hyperfiltration and the diabetic kidney, Diabetes source
The paper’s opening section calls renin–angiotensin system inhibitors the only class then approved for treating diabetic kidney disease and says no other approaches had successfully translated into a new treatment. It also describes RAS inhibition as decompressing the glomerulus, supporting the claim that RAS blockade slows progression. (LLM, conf=0.88)
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A plausible mechanistic explanation for the renoprotective effect of SGLT2 inhibitors is correction of aberrant glomerular haemodynamics induced by hyperglycaemia, which drive progressive nephron loss.34,35”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
What the sources say
- Partly supportedcites [34] Alicic, 2017, Diabetic kidney disease: challenges, progress, and possibilities, Clin J Am Soc Nephrol sourceExperimental — accuracy not yet measured
The Pathophysiology of DKD passage (page unavailable) links hyperglycemia and SGLT2-mediated glucose reabsorption to altered tubuloglomerular feedback, high intraglomerular pressure, and hyperfiltration. A later passage reports that the SGLT2 inhibitor empagliflozin slowed diabetic kidney disease progression, but our copy does not explicitly say that correcting those hemodynamics explains its benefit or that they drive progressive nephron loss. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites [35] Tonneijck, 2017, Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment, J Am Soc Nephrol source
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The absence of effect modification by baseline albuminuria contrasts with the findings from trials of RAS blockade.[31][32][33]”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
What the sources say
- Not checked — no full text of the sourcecites [31] Jafar, 2001, Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease: a meta-analysis of patient-level data, Ann Intern Med source
- Not checked — no full text of the sourcecites [32] Kent, 2007, Progression risk, urinary protein excretion, and treatment effects of angiotensin-converting enzyme inhibitors in nondiabetic kidney disease, J Am Soc Nephrol source
- Partly supportedcites [33] Molitch, 2015, Diabetic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes, Kidney Int sourceExperimental — accuracy not yet measured
The Abstract says the benefit of RAAS blockade for CKD progression in people without increased albumin excretion is unclear, while BP management reports benefits in several trials involving hypertensive diabetic patients. This supports a contrast in the evidence across patient groups, but the paper does not report that baseline albuminuria itself modified the treatment effect; the groups also differ in blood pressure status. Page numbers are not available in our copy. (LLM, conf=0.78)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the absolute benefits of SGLT2 inhibition are likely to be at least as large as those for people with higher eGFRs.30”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
What the sources say
- Partly supportedcites [30] Gansevoort, 2011, Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts, Kidney Int sourceExperimental — accuracy not yet measured
The Discussion reports substantially higher risk of end-stage renal disease at lower eGFR, supporting the claim’s premise that people with lower eGFR have more kidney risk. The paper does not study SGLT2 inhibition or compare its absolute benefits across eGFR groups, so it cannot establish the treatment-benefit comparison. (LLM, conf=0.84)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Because these individuals are at much greater risk of kidney failure than those with higher eGFRs”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
What the sources say
- Supportedcites [30] Gansevoort, 2011, Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts, Kidney Int source
The Discussion reports substantially higher risk of kidney outcomes at eGFR 30–45 than at 45–60 ml/min/1.73m². The paper also reports a sharply rising risk of end-stage renal disease as eGFR falls, supporting the claim about kidney failure. Page numbers were not provided in the copy. (LLM, conf=0.92)
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Large-scale cardio vascular outcome trials [10][11][12][13][14][15] of SGLT2 inhibitors, which were originally designed to meet regulatory requirements and ensure cardiovascular safety, have shown promising effects on a range of albuminuria and serum creatinine-based kidney outcomes in patients with, or at high risk of, atherosclerotic cardiovascular disease.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Introduction
What the sources say
- Supportedcites [10] Perkovic, 2018, Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials, Lancet Diabetes Endocrinol source
The Methods (p. 6) describe the CANVAS Program as two cardiovascular-risk trials, and the Participants section (p. 10) specifies patients with atherosclerotic vascular disease or cardiovascular risk factors. The Findings (p. 6) report lower urinary albumin-to-creatinine ratios and fewer events in a composite that included doubled serum creatinine with canagliflozin. The paper also describes these renal outcomes as exploratory, consistent with the claim’s cautious wording. (LLM, conf=0.92)
- Supportedcites [11] Wanner, 2016, Empagliflozin and progression of kidney disease in type 2 diabetes, N Engl J Med source
The Trial Design and Oversight section describes a cardiovascular-outcome trial of empagliflozin, an SGLT2 inhibitor, in patients with type 2 diabetes and established cardiovascular disease. The Renal Outcomes section reports less progression to macroalbuminuria and fewer serum-creatinine-doubling events with empagliflozin than with placebo. This paper supports the claim as one of the trials cited, rather than as evidence about every SGLT2 inhibitor. (LLM, conf=0.90)
- Supportedcites [12] Neuen, 2018, Cardiovascular and renal outcomes with canagliflozin according to baseline kidney function: data from the CANVAS program, Circulation source
The Methods (Study Design and Participants; Outcomes) describe large cardiovascular safety trials in people with type 2 diabetes and established atherosclerotic disease or cardiovascular risk factors, and specify albuminuria and serum-creatinine-based kidney measures. The Results (Intermediate Outcomes; Renal Outcomes) report reduced albuminuria and lower risk of renal composite outcomes with canagliflozin. The Discussion also places these findings alongside results for another SGLT2 inhibitor. (LLM, conf=0.91)
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The overall effect of SGLT2 inhibitors on substantial loss of kidney function, endstage kidney disease, death due to cardiovascular or kidney disease (overall 29% reduction; figure 2) varied across studies, primarily because of the EMPA-REG OUTCOME trial, in which a greater magnitude of effect on death due to cardiovascular disease was observed (I²=60•3%, p heterogeneity =0•056).”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Results
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SGLT2 inhibitor treatment reduced the risk of end-stage kidney disease by 35% (figure 2), with no differences in treatment effect across studies (I²=0•0%, p heterogeneity =0•41).”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Results
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment with SGLT2 inhibitors also lowered the risk of acute kidney injury by 25% (figure 3), with no evidence of differences between studies (I²=0%, p heterogeneity =0•68).”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Overall
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 12
- It may state two separate claims as one. 23
- The quote only partly states this claim. 1
Every source the paper cites for this claim was checked and supports it.
In the paper
“Two authors (BLN and TY) independently extracted all data using a standardised data form and assessed risk of bias at the study level using the Cochrane risk-of-bias tool.18”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Data analysis
What the sources say
- Supportedcites [18] Higgins, 2011, The Cochrane Collaboration's tool for assessing risk of bias in randomised trials, BMJ source
The citation identifies the Cochrane risk-of-bias tool used by the citing authors. The source paper describes that tool in ‘The risk of bias tool’ and lists its assessment domains in Table 1 (‘Additional information’). The citing authors’ independent data extraction is their own reported procedure, not a claim about this source. (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In 2019, the results of the CREDENCE trial 17 -the first study designed to specifically assess the effect of an SGLT2 inhibitor (canagliflozin) on a primary kidney outcome in people with established diabetic kidney disease-were reported.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Introduction
What the sources say
- Supportedcites [17] Perkovic, 2019, Canagliflozin and renal outcomes in type 2 diabetes and nephropathy, N Engl J Med source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“SGLT2 inhibitors are not currently indicated for people with an eGFR lower than 45 ml/min per 1•73 m² in most countries, largely because of insufficient glycaemic efficacy.29”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
What the sources say
- Partly supportedcites [29] Toyama, 2019, Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and meta-analysis, Diabetes Obes Metab sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says SGLT2 inhibitors were not approved below an eGFR of 45 mL/min/1.73 m² for empagliflozin and canagliflozin, and below 60 for dapagliflozin and ertugliflozin. It also says glucose-lowering efficacy declines with kidney function, while the Abstract identifies that dependence as the primary reason use in CKD has been limited. The copy does not establish the claim’s geographic qualifier, “in most countries,” or explicitly make insufficient glycaemic efficacy the reason for the stated approval thresholds. (LLM, conf=0.84)
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) has been shown to prevent major adverse kidney outcomes in people with diabetes, and these drugs are recommended by clinical practice guidelines for the treatment of people with type 2 diabetes who have, or are at high risk of, kidney disease.[4][5][6][7][8]”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Introduction
What the sources say
- Not checked — no full text of the sourcecites [4] Lewis, 1993, The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy, N Engl J Med source
- Partly supportedcites [5] Lewis, 2001, Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes, N Engl J Med sourceExperimental — accuracy not yet measured
The Results report fewer primary composite events with irbesartan, an ARB, than with placebo or amlodipine in patients with type 2 diabetes and overt nephropathy. The Discussion cautions against assuming ACE inhibitors have equivalent effects in this population. The paper does not establish prevention in people merely at high risk of kidney disease or state a clinical-practice-guideline recommendation. (LLM, conf=0.90)
- Partly supportedcites [6] Brenner, 2001, Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy, N Engl J Med sourceExperimental — accuracy not yet measured
The Discussion (p. 4) reports that losartan, an ARB, reduced end-stage renal disease and doubling of serum creatinine in patients with type 2 diabetes and established nephropathy. The paper does not establish the same major kidney-outcome benefit for ACE inhibitors in this population, address people merely at high risk of kidney disease, or report the claimed clinical-practice guideline recommendation. (LLM, conf=0.88)
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“The effect parallels that seen with RAS blockade, the only other treatment effective in slowing the progression of diabetic kidney disease, and suggests some similarities in mechanisms of action based on reducing intraglomerular pressure”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
What the sources say
- Supportedcites [38] Tuttle, 2017, Back to the future: glomerular hyperfiltration and the diabetic kidney, Diabetes source
In “Back to the Future: Glomerular Hyperfiltration and the Diabetic Kidney,” the paper says RAS inhibition decompresses the glomerulus and SGLT2 inhibitors may reduce hyperfiltration through a different arteriolar mechanism. It also describes empagliflozin’s kidney-function response as consistent with ameliorating intraglomerular hypertension. The opening section identifies RAS inhibitors as the only class then approved for diabetic kidney disease, supporting the comparison in the citing sentence. (LLM, conf=0.91)
hedgedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This haemodynamic effect results in an early fall in eGFR, but is followed by protection against decline in kidney function, with reversal of the haemodynamic effect achieved on drug cessation.12,37”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
What the sources say
- Partly supportedcites [12] Neuen, 2018, Cardiovascular and renal outcomes with canagliflozin according to baseline kidney function: data from the CANVAS program, Circulation sourceExperimental — accuracy not yet measured
The Discussion describes an acute fall in eGFR after SGLT2 inhibition begins, followed by stabilization and preservation of kidney function. The Results report an early fall and a slower subsequent decline with canagliflozin, but although they mention off-treatment measurements, the passages do not state that the haemodynamic effect reversed after drug cessation. (LLM, conf=0.86)
- Supportedcites [37] Fioretto, 2018, Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (chronic kidney disease stage 3a): the DERIVE Study, Diabetes Obes Metab source
The Discussion (page unavailable) describes a transient fall in eGFR with SGLT2 treatment that reverses after discontinuation, and reports long-term eGFR stabilization with dapagliflozin in patients with normal or near-normal renal function. The Results (Safety outcomes; page unavailable) also show eGFR returning to baseline three weeks after treatment stopped. (LLM, conf=0.86)
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Blocking sodium reuptake in the proximal tubule has been suggested to restore delivery of sodium to the macula densa, leading to afferent arteriolar constriction and a reduction in intraglomerular pressure.36”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
What the sources say
- Supportedcites [36] Cherney, 2014, Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus, Circulation source
The paper’s figure description (page not specified in our copy) says that SGLT2 inhibition increases sodium delivery to the macula densa, restoring feedback that can cause afferent vasoconstriction and reduce hyperfiltration. The Discussion describes the resulting GFR reduction as a change in a surrogate marker of intraglomerular pressure, consistent with the citing sentence’s hedged mechanism. (LLM, conf=0.91)
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our systematic review and meta-analysis summarises and pools data from four studies including a total of 38 723 participants across six continents.”
- Also stated in: § Results · plain
“Our meta-analysis included data for a total of 38 723 randomly assigned participants from six continents.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Added value of this study
plainn = 38,723- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, clear, separately significant evidence of benefit was apparent for all eGFR subgroups, including for participants with a baseline eGFR lower than 45 mL/min per 1•73 m², in whom a 30% relative risk reduction was identified (figure 5A).”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Overall
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The results for tests of heterogeneity altered slightly in the different sensitivity analyses (appendix p 11), but the evidence of clear separate benefit for all eGFR subgroups remained constant.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Overall
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: Most participants with baseline eGFR lower than 60 mL/min per 1.73 m² reported without more granular categories were likely to have an eGFR between 45 and <60 mL/min per 1.73 m².
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Acute kidney injury events, both serious and non-serious, were reported variably across individual trials and were not adjudicated (appendix p 9).”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Overall
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Because of the small number of eligible trials, we did not assess publication bias.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Data analysis
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, renoprotection was achieved across all levels of baseline kidney function, down to an eGFR of 30 mL/min per 1•73 m², with clear benefits seen even for the subgroup with baseline eGFR between 30 and 45 mL/min per 1•73 m², for whom these drugs are not currently approved for use in most countries.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The risk of bias was low for all indicators; all participants and investigators were masked to treatment allocation, with complete reporting of outcomes (appendix p 3).”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The protocol for this review was submitted to the International Prospective Register of Systematic Reviews (PROSPERO) for registration before the analyses were initiated (on April 10, 2019), and the study was registered before the analyses were completed (PROSPERO registration number CRD42019131774).”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Search strategy and selection criteria
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Any discrepancies in data extraction or risk-of-bias assessment were resolved in consultation with a third author (MJJ).”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Data analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“However, less than a sixth of participants in the analysis had baseline eGFR lower than 60 mL/min per 1•73 m² and thus, the ability to robustly assess effect modification by kidney function was limited.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Introduction
What the sources say
- Not checked — no full text of the sourcecites [14] Zelniker, 2018, SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials, Lancet source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Most participants in these trials were at low risk of clinically important kidney outcomes and, as a result, event rates for kidney failure were low, with few participants requiring dialysis or kidney transplantation, or dying from kidney disease, in each trial.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Introduction
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Additionally, because very few participants with baseline eGFR lower than 45 mL/min per 1•73 m² were assessed in the cardiovascular outcome trials of SGLT2 inhibitors, whether these patients derive protection against kidney failure outcomes has also been unclear, given that the glycaemic efficacy of SGLT2 inhibitors is substantially attenuated in this population.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The glycaemic efficacy of SGLT2 inhibitors is substantially attenuated in patients with baseline eGFR lower than 45 mL/min per 1.73 m².
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Similarly, most participants in cardiovascular outcome trials of SGTL2 inhibitors had normal albuminuria and, therefore, the consistency of treatment effect across different levels of albuminuria is unclear.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“the large number of events and consistency of effect across the trials is striking and gives confidence to the finding that SGLT2 inhibitors provide protection against acute kidney injury.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Although serious and non-serious acute kidney injury events were investigator reported, collected variably, and not adjudicated”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Sodium-glucose co-transporter-2 (SGLT2) inhibitors are glucose-lowering drugs that also lower blood pressure, bodyweight, and albuminuria and might have direct haemodynamic effects on the kidney. 9”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Introduction
What the sources say
- Not checked — no full text of the sourcecites [9] Heerspink, 2016, Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications, Circulation source
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The results of a 2018 meta-analysis 14 of cardiovascular outcome trials suggested that the effect of SGLT2 inhibitors on kidney outcomes attenuates with declining eGFR.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Introduction
What the sources say
- Not checked — no full text of the sourcecites [14] Zelniker, 2018, SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials, Lancet source
hedgedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The glycaemic efficacy of SGLT2 inhibitors is directly proportional to glomerular filtration rate, 9,28”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
What the sources say
- Not checked — no full text of the sourcecites [9] Heerspink, 2016, Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications, Circulation source
- Not checked — no full text of the sourcecites [28] Heerspink, 2018, Renoprotective effects of sodium-glucose cotransporter-2 inhibitors, Kidney Int source
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The broader generalisability of these results might also be somewhat affected by the characteristics of participants in the included studies”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Because these trials were also not explicitly designed to provide definitive information on renoprotective effects, kidney endpoints were not always prespecified or adjudicated and the distinction between acute and chronic reductions in estimated glomerular filtration rate (eGFR) was not possible in all studies.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Introduction
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These findings strengthen those of a previous meta-analysis 16 of SGLT2 inhibitor cardiovascular outcome trials.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
What the sources say
- Not checked — no full text of the sourcecites [16] Gilbert, 2019, Acute kidney injury with sodium-glucose co-transporter-2 inhibitors: a meta-analysis of cardiovascular outcome trials, Diabetes Obes Metab source
boostedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Although these trials have collectively suggested protection against acute kidney injury, 16 the safety of SGLT2 inhibitors in patients at high risk of adverse kidney outcomes has not been well established.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Introduction
What the sources say
- Not checked — no full text of the sourcecites [16] Gilbert, 2019, Acute kidney injury with sodium-glucose co-transporter-2 inhibitors: a meta-analysis of cardiovascular outcome trials, Diabetes Obes Metab source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The validity of these overview results is reinforced by the high quality of the included studies”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Data for acute kidney injury might be less robust than those for other endpoints, because of variances in the collection and reporting of this outcome.”
§ SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes > Discussion
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
SGLT2 inhibitors are not approved for use in patients with eGFR lower than 45 mL/min per 1.73 m² in most countries, mainly because their glucose-lowering effect is substantially dependent on kidney function.
“Additionally, SGLT2 inhibitors are not approved for use in patients with estimated glomerular filtration rate (eGFR) lower than 45 mL/min per 1•73 m² in most countries, mainly because their glucose-lowering effect is substantially dependent on kidney function.”
The paper relies on this without support.
The glycaemic efficacy of SGLT2 inhibitors is substantially attenuated in patients with baseline eGFR lower than 45 mL/min per 1.73 m².
“given that the glycaemic efficacy of SGLT2 inhibitors is substantially attenuated in this population.”
The authors state this as an assumption.
Most participants with baseline eGFR lower than 60 mL/min per 1.73 m² reported without more granular categories were likely to have an eGFR between 45 and <60 mL/min per 1.73 m².
“on the assumption that most of these participants were likely to have an eGFR within this range (on the basis of trial exclusion criteria).”
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Several large RCTs, which in combination enrolled over 8000 persons, have demonstrated that SGLT2is significantly reduce the risk of CV death or worsening HF and improve symptoms, physical limitations, and QoL in persons with heart failure with reduced ejection fraction (HFrEF).”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [457]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The benefits were highly consistent in persons both with and without T2D; however, because persons with T2D had higher absolute risk, they experienced a greater absolute benefit with SGLT2is vs placebo.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [457]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Subgroup meta-analyses based on participants ' kidney function indicated that the salutary effects of SGLT2i on MACE, cardiovascular death or HHF, and a composite kidney outcome (substantial loss of kidney function, end-stage kidney disease, or death due to kidney disease) do not signi fi cantly differ among subgroups based on eGFR (142,252).”
From Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2022) · cites this paper as [252]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Even with current therapies available [6–10], patients with T2DM and chronic kidney disease (CKD) still experience a significant cardiovascular and renal morbidity and mortality.”
From Network meta-analysis on the effects of finerenone versus SGLT2 inhibitors and GLP-1 receptor agonists on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and chronic kidney disease (2022) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“By decreasing glucose and sodium reabsorption, SGLT2 inhibitors decrease tubular workload and oxygen consumption and alleviate hypoxia, which may explain why SGLT2 inhibitors decrease proximal biomarkers of AKI such as kidney injury molecule-1 and decrease the risk of AKI events (Neuen et al., 2019; Dekkers et al., 2018).”
From A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors (2021) · cites this paper as Neuen et al., 2019
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Patients with chronic kidney disease (CKD) and type 2 diabetes have high residual cardiorenal morbidity and mortality, despite current therapies,1–5”
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 [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Evidence from combined major SGLT2i trials, however, suggests that kidney and cardiovascular benefits are consistent irrespective of baseline albuminuria (56), including in patients with normal albumin excretion, as reflected in the KDIGO recommendation and consensus statement supporting SGLT2i use in most patients with T2D and CKD (2).”
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 [56]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Moreover, SGLT2i have been observed to have consistent efficacy and safety across studied ranges of eGFR (56).”
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 [56]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Based on these results, direct evidence supporting initiation of an SGLT2i for patients with T2D and eGFR 20–29 mL/min/1.73 m2 is strongest for patients with concomitant albuminuria or HF, though the efficacy and safety of SGLT2i are generally consistent among trial participants with or without these conditions (56,61,62).”
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 [56]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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”
From Dapagliflozin in Patients with Chronic Kidney Disease (2020) · cites this paper as [16]
The cited source says what the claim attributes to it.
In the citing paper
“Consistency is moderate to high, with consistency of kidney bene fi t across the trials and by baseline eGFR and albuminuria groups.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [97]
The cited source says what the claim attributes to it.
In the citing paper
“found that SGLT2i signi fi cantly reduced the risk of dialysis, kidney transplant, or death from kidney causes by 33% (RR: 0.67; 95% CI: 0.52 -0.86).”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [97]
The cited source says what the claim attributes to it.
In the citing paper
“There was also reduction in kidney failure and AKI.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [97]
The cited source says what the claim attributes to it.
In the citing paper
“The bene fi ts of SGLT2i on kidney outcomes were seen across all eGFR subgroups, 97 including those with an eGFR of 30 -45 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 [97]
The cited source says what the claim attributes to it.
In the citing paper
“Pooled results of the 4 large RCTs that published results on kidney outcomes also demonstrated that risk of AKI is signi fi cantly lower with SGLT2i treatment.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [97]
The cited source says what the claim attributes to it.
In the citing paper
“Despite this theoretical concern, clinical trials have shown that the incidence of AKI is decreased with SGLT2i, compared with placebo.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [97]
The cited source says what the claim attributes to it.
In the citing paper
“In fact, SGLT2i use appears to protect patients from AKI (56).”
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In the DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) trial, dapagliflozin reduced the primary endpoint of CV death or worsening HF by 26%, whereas in EMPEROR-REDUCED (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), empagliflozin significantly reduced the risk of CV death or hospitalization for HF by 25%.457,470”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [457]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In the DAPA-HF (Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure) trial, dapagliflozin reduced the primary endpoint of CV death or worsening HF by 26%, whereas in EMPEROR-REDUCED (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), empagliflozin significantly reduced the risk of CV death or hospitalization for HF by 25%.457,470”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [457]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Dapagliflozin also has shown in people with HFrEF reduced risk of worsening HF or death from CV causes regardless of the presence or absence of DM.457”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [457]
Experimental — accuracy not yet measuredIn the citing paper
“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”
In the citing paper
“Another limitation of previous meta-analyses was the inability to standardise between-trial differences in the thresholds of eGFR decrease used to define kidney disease progression within categorical composite outcomes (appendix p 9).1, 6”
In the citing paper
“In CREDENCE, 29.8% (1,313/4,401) of participants had a baseline eGFR of 30 to 45 mL/min/1.73 m2, and kidney benefits did not differ from those in patients with higher eGFR (14,69).”
From SGLT2 inhibition for CKD and cardiovascular disease in type 2 diabetes: report of a scientific workshop sponsored by the National Kidney Foundation (2021) · cites this paper as [69]
In the citing paper
“Despite theoretical concerns for acute kidney injury and urinary tract infection, SGLT2 inhibitors do not increase these risks and acute kidney injury is less common (69,95).”
From SGLT2 inhibition for CKD and cardiovascular disease in type 2 diabetes: report of a scientific workshop sponsored by the National Kidney Foundation (2021) · cites this paper as [69]
In the citing paper
“Higher risks for amputation and fracture were not observed in CVOTs of other SGLT2 inhibitors or with canagliflozin in the CREDENCE trial (14,69,95).”
From SGLT2 inhibition for CKD and cardiovascular disease in type 2 diabetes: report of a scientific workshop sponsored by the National Kidney Foundation (2021) · cites this paper as [69]
In the citing paper
“On the contrary, large clinical trials and meta-analyses have demonstrated that SGLT2 inhibitors reduce the incidence of AKI (Neuen et al., 2019).”
From A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors (2021) · cites this paper as Neuen et al., 2019
Citations
Cites
The Cochrane Collaboration's tool for assessing risk of bias in randomised trials
Higgins, J. P. T., Altman, D. G., Gotzsche, P. C., Juni, P., Moher, D., Oxman, A. D., Savovic, J., Schulz, K. F., Weeks, L., Sterne, J. A. C., et al. (2011) · BMJ · doi:10.1136/bmj.d5928 · Cited by 33,817
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504720 · Cited by 12,315
Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes
Neal, B., Perkovic, V., Mahaffey, K. W., de Zeeuw, D., Fulcher, G., Erondu, N., Shaw, W., Law, G., Desai, M., & Matthews, D. R. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1611925 · Cited by 7,830
Self-citationBrenner, B. M., Cooper, M. E., de Zeeuw, D., Keane, W. F., Mitch, W. E., Parving, H.-H., Remuzzi, G., Snapinn, S. M., Zhang, Z., & Shahinfar, S. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011161 · Cited by 7,493
Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes
Wiviott, S. D., Raz, I., Bonaca, M. P., Mosenzon, O., Kato, E. T., Cahn, A., Silverman, M. G., Zelniker, T. A., Kuder, J. F., Murphy, S. A., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812389 · Cited by 6,382
Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. J. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1811744 · Cited by 6,189
Self-citationLewis, E. J., Hunsicker, L. G., Clarke, W. R., Berl, T., Pohl, M. A., Lewis, J. B., Ritz, E., Atkins, R. C., Rohde, R., & Raz, I. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011303 · Cited by 5,987
The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy
Lewis, E. J., Hunsicker, L. G., Bain, R. P., & Rohde, R. D. (1993) · New England Journal of Medicine · doi:10.1056/nejm199311113292004 · Cited by 5,394
Webster, A. C., Nagler, E. V., Morton, R. L., & Masson, P. (2017) · The Lancet · doi:10.1016/s0140-6736(16)32064-5 · Cited by 3,842
Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes
Wanner, C., Inzucchi, S. E., Lachin, J. M., Fitchett, D., von Eynatten, M., Mattheus, M., Johansen, O. E., Woerle, H. J., Broedl, U. C., & Zinman, B. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1515920 · Cited by 3,655
Research works printed but not linked: 1
- Wanner, 2016, Empagliflozin and progression of kidney disease in type 2 diabetes—authors reply, N Engl J Med, 375, 1801, 10.1056/NEJMoa1515920 · DOI · Paper page
Cited by
Sorted by citations
Dapagliflozin in Patients with Chronic Kidney Disease
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., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2024816 · Cited by 5,618
Self-citationDavies, M. J., Aroda, V. R., Collins, B. S., Gabbay, R. A., Green, J., Maruthur, N. M., Rosas, S. E., Del Prato, S., Mathieu, C., Mingrone, G., et al. (2022) · Diabetes Care · doi:10.2337/dci22-0034 · Cited by 2,104
“Subgroup meta-analyses based on participants’ kidney function indicated that the salutary effects of SGLT2i on MACE, cardiovascular death or HHF, and a composite kidney outcome (substantial loss of kidney function, end-stage kidney disease, or death due to kidney disease) do not significantly differ among subgroups ba…”
BackgroundZannad, F., Ferreira, J. P., Pocock, S. J., Anker, S. D., Butler, J., Filippatos, G., Brueckmann, M., Ofstad, A. P., Pfarr, E., Jamal, W., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)31824-9 · Cited by 1,408
KDIGO 2020 Clinical practice guideline for diabetes management in chronic kidney disease
de Boer, I. H., Caramori, M. L., Chan, J. C. N., Heerspink, H. J. L., Hurst, C., Khunti, K., Liew, A., Michos, E. D., Navaneethan, S. D., Olowu, W. A., et al. (2020) · Kidney International · doi:10.1016/j.kint.2020.06.019 · Cited by 1,399
Self-citationKDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease
Rossing, P., Caramori, M. L., Chan, J. C. N., Heerspink, H. J. L., Hurst, C., Khunti, K., Liew, A., Michos, E. D., Navaneethan, S. D., Olowu, W. A., et al. (2022) · Kidney International · doi:10.1016/j.kint.2022.06.008 · Cited by 1,373
Self-citation
Metadata
- Authors
- Neuen, B. L., Young, T., Heerspink, H. J. L., Neal, B., Perkovic, V., Billot, L., Mahaffey, K. W., Charytan, D. M., Wheeler, D. C., Arnott, C., Bompoint, S., Levin, A., & Jardine, M. J.
- Affiliations
- UNSW Sydney (AU)
- University Medical Center Groningen (NL)
- The University of Sydney (AU)
- Stanford Medicine (US)
- NYU Langone Health (US)
- University College London (GB)
- University of British Columbia (CA)
- Concord Repatriation General Hospital (AU)
- Corresponding author
- Jardine, Meg J
- ORCID
- Venue
- The Lancet Diabetes & Endocrinology
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 7
- Issue
- 11
- Pages
- 845-854
- ISSN
- 2213-8587 (ISSN-L)
- OpenAlex
- W2971414122
- Cited by
- 893
- References
- 46
- Citations by year
- 2026: 65 · 2025: 86 · 2024: 104 · 2023: 142 · 2022: 164 · 2021: 185 · 2020: 125 · 2019: 17
- FWCI
- 18.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Lancet Diabetes & Endocrinology (publishedVersion, other-oa)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- UCL Discovery (University College London) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- National Health and Medical Research Council
- AstraZeneca
- University of New South Wales
- Janssen Pharmaceuticals
- Boehringer Ingelheim
- University of Oxford
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- SGLT2 inhibitors, type 2 diabetes, renal failure, end-stage renal disease, acute kidney injury, dialysis, kidney transplantation, kidney disease mortality, estimated glomerular filtration rate, albuminuria, renin-angiotensin system blockade, empagliflozin, canagliflozin, dapagliflozin, effect modification
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Diabetic Nephropathies, Humans, Kidney Failure, Chronic, Randomized Controlled Trials as Topic
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.
A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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
