The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index; 3 of the 7 sources its claims cite were checked for support.
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
Open accessAbstract
BACKGROUND: The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known. METHODS: We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin group versus the placebo group. The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina. RESULTS: A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P=0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction). There was no significant between-group difference in the key secondary outcome (P=0.08 for superiority). Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events. CONCLUSIONS: Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care. (Funded by Boehringer Ingelheim and Eli Lilly; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.).
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Claims the paper makes
3 of 7 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Evidence that glucose lowering reduces the rates of cardiovascular events and death has not been convincingly shown, 4-6”
What the sources say
- Partly supportedcites [4] sourceExperimental — accuracy not yet measured
The Results (p. 1) report that sitagliptin lowered glycated hemoglobin but did not reduce the primary cardiovascular outcome; Other Secondary Outcomes (p. 4) show no reduction in death from any cause. These findings support the lack of a demonstrated benefit for sitagliptin in this trial, but do not establish the broader claim about glucose lowering generally. (LLM, conf=0.83)
- Not checked — no full text of the sourcecites [5] source
- Supportedcites [6] source
The paper says uncertainty remains about whether glucose-lowering strategies can reduce cardiovascular risk; it notes that most trials had not shown a significant cardiovascular benefit, while acknowledging possible exceptions for metformin and insulin. The Discussion likewise says that whether improved glycemic control reduces macrovascular events remains in question. Its reported death outcomes do not show a significant reduction. (LLM, conf=0.90)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly 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
“| Fatal or nonfatal stroke | 69 (3.0) | 10.5 | 164 (3.5) | 12.3 | 1.18 (”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“P<0.001 for noninferiority”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“A sensitivity analysis of death from any cause in which it was assumed that all patients who were lost to follow-up in the empagliflozin group died and all patients who were lost to follow-up in the placebo group were alive showed a significant benefit of empagliflozin versus placebo (hazard ratio, 0.77; 95% CI, 0.65 to 0.93; P = 0.005).”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- The authors state this as an assumption: In the sensitivity analysis of death from any cause, all patients lost to follow-up in the empagliflozin group were assumed to have died and all patients lost to follow-up in the placebo group were assumed to be alive.
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
“In subgroup analyses, there was some heterogeneity for the primary outcome.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“There was no significant between-group difference in the key secondary outcome (P = 0.08 for superiority).”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“There were no relevant changes in electrolytes in the two study groups.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“All categories of death from cardiovascular causes contributed to the reduction in cardiovascular death in the empagliflozin group”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“Among patients with type 2 diabetes at high risk for cardiovascular events, those receiving empagliflozin had a lower rate of the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke than did patients receiving placebo.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“with no significant between-group difference in the risk of myocardial infarction or stroke.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 16
- The quote only partly states this claim. 4
- It may state two separate claims as one. 20
Every source the paper cites for this claim was checked and supports it.
In the paper
“Inhibitors of sodium-glucose cotransporter 2 reduce rates of hyperglycemia in patients with type 2 diabetes by decreasing renal glucose reabsorption, thereby increasing urinary glucose excretion. 10”
What the sources say
- Supportedcites [10] source
The Introduction states that SGLT2 inhibitors block renal glucose reabsorption, increase urinary glucose excretion, and have anti-hyperglycaemic effects. The Conclusion also states that SGLT2 inhibition lowers renal glucose reabsorption and blood glucose levels and may be effective in type 2 diabetes. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- 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
“Genital infection was reported in a higher percentage of patients in the pooled empagliflozin group.”
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
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
“A higher percentage of patients in the placebo group received additional glucose-lowering medications (including sulfonylurea and insulin), antihypertensive medications (including diuretics), and anticoagulants during the trial, with no between-group difference in the receipt of lipidlowering drugs”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“Over the course of the study, empagliflozin, as compared with placebo, was associated with small reductions in weight, waist circumference, uric acid level, and systolic and diastolic blood pressure with no increase in heart rate and small increases in both LDL and HDL cholesterol”
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“at week 206, the differences were -0.24 percentage points (95% CI, -0.40 to -0.08) and -0.36 percentage points (95% CI, -0.51 to -0.20).”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“Myocardial infarction was reported in 4.8% of patients in the empagliflozin group and 5.4% of those in the placebo group, and stroke in 3.5% and 3.0% of patients, respectively.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“Urosepsis was reported in 0.4% of patients in the empagliflozin group and 0.1% of those in the placebo group, but there was no imbalance in overall rates of urinary tract infection, complicated urinary tract infection, or pyelonephritis”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“After 12 weeks, during which glucose-lowering therapy was to remain unchanged, the adjusted mean differences in the glycated hemoglobin level between patients receiving empagliflozin and those receiving placebo were -0.54 percentage points (95% CI, -0.58 to -0.49) in the 10-mg group and -0.60 percentage points (95% CI, -0.64 to -0.55) in the 25-mg group”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction)”
- Also stated in: § CONCLUSIONS · p. 1 · plain
“Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
- Also stated in: § CONCLUSIONS · p. 1 · 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
“The proportions of patients who had adverse events, serious adverse events, and adverse events leading to the discontinuation of a study drug were similar in the empagliflozin group and the placebo group”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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 proportions of patients with diabetic ketoacidosis, volume depletion, thromboembolic events, and bone fracture were low (ranging from <1% for ketoacidosis and thromboembolic events to 5% for volume depletion) and similar in the empagliflozin groups and the placebo group.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events.”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“There were no significant between-group differences in the rates of myocardial infarction or stroke”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction)”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
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
“Hematocrit values were higher in the empagliflozin groups than in the placebo group”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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 proportions of patients with confirmed hypoglycemic adverse events, acute renal failure, diabetic ketoacidosis, thromboembolic events, bone fracture, and events consistent with volume depletion were similar in the two study groups.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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 percentage of patients with acute renal failure (including acute kidney injury) was lower in the empagliflozin groups than in the placebo group, and renal function was maintained with empagliflozin.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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 hazard ratios for the primary outcome were 0.85 (95% CI, 0.72 to 1.01; P = 0.07) for the 10-mg dose of empagliflozin versus placebo and 0.86 (95% CI, 0.73 to 1.02; P = 0.09) for the 25-mg dose versus placebo.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction)”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
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
“and the point estimate for the hazard ratio for stroke was closer to 1.00”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“For the primary and key secondary outcomes, hazard ratios for the comparison between the 10-mg dose of empagliflozin versus placebo and the 25-mg dose versus placebo were virtually identical to those in the pooled analysis, but the individual dose effects were not significant”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“there is concern that intensive glucose lowering or the use of specific glucose-lowering drugs may be associated with adverse cardiovascular outcomes. 8”
What the sources say
- Not checked — no full text of the sourcecites [8] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“Empagliflozin is a selective inhibitor of sodium glucose cotransporter 2 11”
What the sources say
- Not checked — no full text of the sourcecites [11] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Randomization was performed with the use of a computer-generated random-sequence and interactive voice- and Web-response system and was stratified according to the glycated hemoglobin level at screening (<8.5% or ≥8.5%), bodymass index at randomization (<30 or ≥30), renal function at screening (eGFR, 30 to 59 ml, 60 to 89 ml, or ≥90 ml per minute per 1.73 m 2 ), and geographic region”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. 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
“We performed the primary analysis using a modified intention-to-treat approach among patients who had received at least one dose of a study drug.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
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
“but these numbers cannot be extrapolated to patient populations with other clinical characteristics.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
In the paper
“Cardiovascular outcome events and deaths were prospectively adjudicated by two clinical-events committees (one for cardiac events and the other for neurologic events), as recommended by the Food and Drug Administration (FDA) guidelines. 9”
What the sources say
- Not matchedcites [9]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Not matched
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 median duration of treatment was 2.6 years, and the median observation time was 3.1 years; both durations were similar in the pooled empagliflozin group and the placebo group”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“Members of the University of Freiburg conducted an independent statistical analysis of cardiovascular outcomes”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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 trial was conducted in accordance with the principles of the Declaration of Helsinki and the the International Conference on Harmonisation Good Clinical Practice guidelines and was approved by local authorities. An independent ethics committee or institutional review board approved the clinical protocol at each participating center.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“this was a randomized, double-blind, placebo-controlled trial”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“Our trial provides data to support the longterm use of empagliflozin, as well as strong evidence for a reduction in cardiovascular risk.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Overall, 97.0% of patients completed the study, with 25.4% of patients prematurely discontinuing a study drug. Final vital status was available for 99.2% of patients.”
Strength:plain· not yet calibratedn = 7,028Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“Safety data were reviewed by an independent academic data monitoring committee every 90 days or at the discretion of the committee.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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 trial continued until an adjudicated primary outcome event had occurred in at least 691 patients.”
Strength:plain· not yet calibratedn = 691Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Analyses were based on a Cox proportional-hazards model, with study group, age, sex, baseline body-mass index, baseline glycated hemoglobin level, baseline eGFR, and geographic region as factors.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
The paper relies on this without support.
The effects of empagliflozin, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk were not known before this trial.
“The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.”
The authors state this as an assumption.
In the sensitivity analysis of death from any cause, all patients lost to follow-up in the empagliflozin group were assumed to have died and all patients lost to follow-up in the placebo group were assumed to be alive.
“A sensitivity analysis of death from any cause in which it was assumed that all patients who were lost to follow-up in the empagliflozin group died and all patients who were lost to follow-up in the placebo group were alive”
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 cited source doesn’t support the claim as written.
In the citing paper
“and the risk of reduction in eGFR, ESKD, or death from ESKD by 40%”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [111]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe cited source doesn’t support the claim as written.
In the citing paper
“It is important to note that Black Americans were underrepresented in this trial comprising only 3.3% of all participants and that this trend towards greater amputations was not found in subsequent analyses.”
From Racial and Ethnic Disparities in Peripheral Artery Disease (2021) · cites this paper as [94]
Checked by a reasoning model — may be wrong.
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 time to benefit emerged earlier in that trial than in the present trial”
From Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (2016) · cites this paper as [12]
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
“In recent years, sodium–glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor antagonists (GLP-1RAs) have demonstrated benefits in preventing deleterious cardiorenal endpoints among individuals with type 2 diabetes, shifting disease management from a glucocentric approach to one that prioritises long-term cardiorenal health [5–7].”
From Racial and ethnic disparities in the uptake of SGLT2is and GLP-1RAs among Medicare beneficiaries with type 2 diabetes and heart failure, atherosclerotic cardiovascular disease and chronic kidney disease, 2013–2019 (2025) · cites this paper as [6]
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
“and the risk of doubling of serum creatinine accompanied by eGFR #45 mL/min/1.73m 2 by 44%”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [111]
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
“There is substantial evidence con fi rming that SGLT2i confer signi fi cant kidney and heart protective effects in these patients.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [90]
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
“As discussed, there have now been 4 RCTs 87,89,90,93 and a meta-analysis of 4 of these trials 97 that have con fi rmed the signi fi cant bene fi ts of SGLT2i on clinically meaningful kidney outcomes beyond just proteinuria as a surrogate marker.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [90]
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 recommendation is strong due to the known kidney and/or cardiovascular protective effects in patients with T2D and CKD as shown in high-quality trials, such as EMPA-REG, CANVAS, DECLARE-TIMI 58, CREDENCE, DAPA-CKD, SCORED, DAPA-HF, SOLOIST, EMPEROR-Reduced and EMPEROR-Preserved.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [90]
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 similar rates of amputation and fracture that we observed with canagliflozin and placebo are reassuring and consistent with trials of other SGLT2 inhibitors 6,7,20 but differ from the CANVAS Program findings.5”
From Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy (2019) · cites this paper as [6]
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
“SGLT2 inhibitors reduce the incidence of heart failure and improve heart failurerelated outcomes, including hospitalization for heart failure and heart failure-related symptoms, in people with diabetes with preserved or reduced ejection fraction (250,(255)(256)(257)(298)(299)(300)(301)(302)(303)(304)(305)(306).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [255]
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
“In the EMPA-REG OUTCOME trial, only 10% of study participants had a prior history of heart failure, and treatment with empagliflozin reduced the relative risk for hospitalization from heart failure by 35% (281).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [281]
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
“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 [10]
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
“Stratified analyses of the trials of this drug class indicate that older adults have similar or greater benefits than younger people (116-118).”
From 13. Older Adults: Standards of Care in Diabetes—2024 (2024) · cites this paper as [116]
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
“Stratified analyses of the trials of this drug class indicate that older adults have similar or greater benefits than younger people”
From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [139]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Clinical trials of other SGLT2 inhibitors have shown similar results.8,10,19”
From Dapagliflozin in Patients with Chronic Kidney Disease (2020) · cites this paper as [19]
The cited source says what the claim attributes to it.
In the citing paper
“The pattern of cardiovascular benefits that were associated with liraglutide in our trial appears to differ from that with the sodium–glucose cotransporter 2 inhibitor empagliflozin in the previously reported EMPA-REG OUTCOME trial.”
From Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (2016) · cites this paper as [12]
The cited source says what the claim attributes to it.
In the citing paper
“the heterogeneity of the direction and magnitude of the effects on the components of the primary composite outcome in that trial contrasts with the consistency of the effect in the present trial.”
From Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (2016) · cites this paper as [12]
The cited source says what the claim attributes to it.
In the citing paper
“The SGLT2i cardiovascular outcome trials (CVOTs) have reported DKA rates of 0.1 -0.6% compared with rates of < 0.1 -0.3% with placebo (143 -147), with very low rates in the HF (148 -151) and CKD (152,153) outcome studies.”
The cited source says what the claim attributes to it.
In the citing paper
“Pharmaceutical interventions of 1.5 to 3 years duration report HbA1c reductions of 0.2 to 1.0% with DPP-4 inhibitors, SGLT-2 inhibitors and GLP-1 agonists (6, 7, 49).”
The cited source says what the claim attributes to it.
In the citing paper
“Participants with T2D and an eGFR as low as 30 ml/min per 1.73 m 2 were included in the EMPA-REG, CANVAS, and CREDENCE trials, 87,90,93 and ef fi cacy and safety in these studies were consistent across both eGFR and albuminuria down to this threshold.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [90]
The cited source says what the claim attributes to it.
In the citing paper
“The EMPA-REG OUTCOME trial also showed that empagliflozin was superior to placebo, 6”
From Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy (2019) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“Recently, trials evaluating a sodium-glucose cotransporter 2 inhibitor (empagliflozin) and a glucagon-like peptide 1 (GLP-1) analogue (liraglutide) have shown improved cardiovascular outcomes in patients with type 2 diabetes who were at high risk for cardiovascular events.2,3”
From Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (2016) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“To date, two antihyperglycemic agents have been shown to reduce the rate of cardiovascular events in patients with type 2 diabetes at high cardiovascular risk.2,3”
From Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (2016) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“The BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) showed that treatment with empagliflozin reduced the composite outcome of MI, stroke, and cardiovascular death by 14% (absolute rate 10.5% vs. 12.1% in the placebo group, HR in the empagliflozin group 0.86 [95% CI 0.74-0.99];P = 0.04 for superiority) and cardiovascular death by 3”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [255]
The cited source says what the claim attributes to it.
In the citing paper
“In the EMPA-REG OUTCOME trial, only 10% of study participants had a prior history of heart failure, and treatment with empagliflozin reduced the relative risk for hospitalization from heart failure by 35% (255).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [255]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Specifically, compared with placebo, empagliflozin reduced the risk of incident or worsening nephropathy (a composite of progression to UACR >300 mg/g creatinine, doubling of serum creatinine, ESKD, or death from ESKD) by 39%”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [111]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“canagliflozin reduced the risk of progression of albuminuria by 27%”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [111]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“and semaglutide reduced the risk of new or worsening nephropathy (a composite of persistent UACR >300 mg/g creatinine, doubling of serum creatinine, or ESKD) by 36% (each P < 0.01).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [111]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“liraglutide reduced the risk of new or worsening nephropathy (a composite of persistent macroalbuminuria, doubling of serum creatinine, ESKD, or death from ESKD) by 22%”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [111]
Experimental — accuracy not yet measuredIn the citing paper
“Among patients with type 2 diabetes at high risk for cardiovascular events, SGLT2 inhibitor use has been shown to significantly reduce death from cardiovascular causes and to lower the risk of hospitalization for heart failure and progression of kidney disease.4,6”
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 [4]
In the citing paper
“Given the additional beneficial effects of GLP-1 RAs and SGLT2 inhibitors on CV outcomes in T2DM (Section 5.3), these agents should be the preferred glucose-lowering medication in overweight and obese patients with CVD and T2DM, as obesity medications have, to date, not shown to reduce CV events.[70][71][72]”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [71]
In the citing paper
“Empagliflozin reduced the risk of HF hospitalization by 35% in patients with and without previous HF.71”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [71]
In the citing paper
“SGLT2 inhibitors, compared with placebo, were associated with more new-onset AF cases in EMPA-REG OUTCOME (empagliflozin vs. placebo), but fewer incident AF cases in CANVAS (canagliflozin vs. placebo) and DECLARE-TIMI 58 (dapagliflozin vs. placebo).71,151,153,603”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [71]
In the citing paper
“In the CRIC (Chronic Renal Insufficiency Cohort) study, approximately 40% of participants with established CKD had apparent treatment-resistant hypertension.22”
From Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights From the CREDENCE Trial (2021) · cites this paper as [22]
In the citing paper
“The pattern of use of BP lowering therapies and prevalence of resistant hypertension in CREDENCE is consistent with these data, and suggest that our findings are likely to be directly applicable to the routine care of patients with T2DM and CKD, where the burden of resistant hypertension and use of multiple BP lowering therapies is high.”
From Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights From the CREDENCE Trial (2021) · cites this paper as [22]
In the citing paper
“The CVOTs designed to test safety and a CKD trial (CREDENCE) were comparable in key aspects: participants with T2DM, placebo controls, SGLT2 inhibitor dose not based on glycemia, all participants treated by standard of care, and similarly defined and adjudicated outcomes.”
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 [35]
In the citing paper
“After a median follow-up of 3.1 years, patients treated with empagliflozin had a 14% lower relative risk for cardiovascular death, myocardial infarction, or stroke (hazard ratio [HR], 0.86; 95% CI, 0.74–0.99) (35).”
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 [35]
In the citing paper
“Diuresis is an important mechanism for reducing blood pressure and risk for HF events (11–16,35).”
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 [35]
In the citing paper
“The benefit of empagliflozin on the primary CVD composite outcome was largely driven by a significant reduction in CVD death rates (3.7% vs. 5.9%; HR, 0.62 [95% CI, 0.49–0.77]).”
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 [35]
In the citing paper
“cardiovascular event rates remain high, even among the patients with well-managed T2DM enrolled in contemporary outcomes trials,8–10”
In the citing paper
“several cardiovascular outcomes trials (CVOTs) demonstrated that drugs that lowered HbA1c to similar levels had different effects on cardiovascular outcomes”
In the citing paper
“empagliflozin reduced MACEs by 14% (HR, 0.86 [95% CI, 0.75–0.99]) in patients with established cardiovascular disease”
In the citing paper
“which was driven primarily by a significant reduction in cardiovascular mortality (3.7% versus 5.9%; 38% RRR)”
In the citing paper
“Empagliflozin also reduced all-cause mortality (5.7% versus 8.3%; 32% RRR)”
In the citing paper
“Large cardiovascular outcome trials provided initial proof that SGLT2 inhibitors slow the progression of kidney function decline and reduce the risks of kidney outcomes in patients with T2D of whom the majority had relatively preserved kidney function (Wiviott et al., 2019; Neal et al., 2017; Zinman et al., 2015; Mosenzon et al., 2019).”
From A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors (2021) · cites this paper as Zinman et al., 2015
In the citing paper
“A limitation of our study is that it was started before GLP-1 receptor agonists 24 and SGLT2 inhibitors 25 were shown to reduce major cardiovascular events and mortality in patients with stable cardiovascular disease and type 2 diabetes.”
In the citing paper
“Rates of heart failure hospitalization have been improved in recent trials including people with type 2 diabetes, most of whom also had ASCVD, with sodium -glucose cotransporter 2 (SGLT2) inhibitors (8 -11).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [8]
In the citing paper
“and cardiovascular death by 38% (absolute rate 3.7% vs. 5.9%, HR 0.62 [95% CI 0.49 -0.77]; P < 0.001) (8).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [8]
In the citing paper
“EMPA-REG OUTCOME showed that over a median follow-up of 3.1 years, treatment reduced the composite outcome of MI, stroke, and cardiovascular death by 14% (absolute rate 10.5% vs. 12.1% in the placebo group, HR in the empagli fl ozin group 0.86 [95% CI 0.74 -0.99]; P = 0.04 for superiority)”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [8]
In the citing paper
“In EMPAREG OUTCOME, the addition of empaglifl ozin to standard care led to a signi fi cant 35% reduction in hospitalization for heart failure compared with placebo (8).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [8]
In the citing paper
“Reduced incidence of heart failure has been observed with the use of SGLT2 inhibitors (8,194,196).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [8]
In the citing paper
“However, a longer duration of 8–15 years after strict glycemic control is necessary for the suppression of ASCVD risk797, 798).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [797]
In the citing paper
“Not all DPP4 inhibitors are associated with higher rates of HF (Table 8).16 -24,184-186”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [20]
In the citing paper
“In the EMPA-REG OUTCOME trial (n=7020), including patients with T2DM, established CV disease and eGFR >30 mL/min/1.73m 2 , there was a major reduction in HF hospitalization (HR 0.65) with empagliflozin compared with placebo.20”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [20]
In the citing paper
“A significant breakthrough in contemporary cardiology was the finding that some T2DM drugs are associated with a lower risk of HF hospitalization in patients with CV disease or at high risk of CV disease (Table 8).”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [20]
In the citing paper
“Two large RCTs that assessed CV safety of the sodium-glucose co-transporter type 2 (SGLT2) inhibitors, empagliflozin and canagliflozin, have shown a significant reduction in HF hospitalization with both drugs.20,189”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [20]
In the citing paper
“Empagliflozin in EMPA-REG OUTCOME, but not canagliflozin in CANVAS, reduced all-cause and CV mortality as well as HF hospitalization.”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [20]
In the citing paper
“Darapladib (which targeted Lp-PLA 2 ) failed in SOLID-TIMI 52 128 and STABILITY 129 trials”
From Integrating genomics with biomarkers and therapeutic targets to invigorate cardiovascular drug development (2021) · cites this paper as [128]
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“ii) HHF [Grade B, Level 2 (12,15,17) for empagliflozin,”
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Metadata
- Authors
- Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J., Broedl, U. C., & Inzucchi, S. E.
- Affiliations
- Mount Sinai Hospital (CA)
- University of Würzburg (DE)
- George Washington University (US)
- University of Toronto (CA)
- Boehringer Ingelheim (Germany) (DE)
- Boehringer Ingelheim (United States) (US)
- Boehringer Ingelheim (Norway) (NO)
- Yale University (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2015-11-26
- Volume
- 373
- Issue
- 22
- Pages
- 2117-2128
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2146264128
- Semantic Scholar
- b43c548120609d766a5fec5a495baa81903ab3f2
- Cited by
- 12,315
- References
- 28
- Citations by year
- 2026: 741 · 2025: 1017 · 2024: 1082 · 2023: 1131 · 2022: 1300 · 2021: 1451 · 2020: 1380 · 2019: 1206 · 2018: 1069 · 2017: 948 · 2016: 688 · 2015: 87
- FWCI
- 567.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- Research Bank (Australian Catholic University) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Keywords
- empagliflozin, SGLT2 inhibitors, type 2 diabetes, cardiovascular outcomes, cardiovascular mortality, heart failure hospitalization, myocardial infarction, stroke
- MeSH terms
- Aged, Benzhydryl Compounds, Cardiovascular Diseases, Cause of Death, Diabetes Mellitus, Type 2
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