CoChat
Sign Up
Cited by 12,315Diabetes Treatment and ManagementDiabetes Management and ResearchHyperglycemia and glycemic control in critically ill and hospitalized patients

Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes

Open access
Zinman, Bernard, Wanner, Christoph, Lachin, John M., Fitchett, David, Bluhmki, Erich, Hantel, Stefan, Mattheus, Michaela, Devins, Theresa +4 more·2015·New England Journal of Medicine
DOI 10.1056/nejmoa1504720
Open this paper in CoChat — free accountOpen PDF

Abstract

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.).

Integrity signals

Registry

Crossref · 10.1056/nejmoa1504720

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

2 of 7 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured

  • Premisecitation
    § ABSTRACT · p. 2

    Evidence that glucose lowering reduces the rates of cardiovascular events and death has not been convincingly shown.

    “Evidence that glucose lowering reduces the rates of cardiovascular events and death has not been convincingly shown, 4-6”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [4] source

      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)

      Experimental — accuracy not yet measured
    • cites [5] source
    • cites [6] source
  • Findingown data
    § Cardiovascular Outcomes · p. 6

    There was no significant between-group difference in fatal or nonfatal stroke (HR 1.18; 95% CI 0.89-1.56; P=0.26).

    “| Fatal or nonfatal stroke | 69 (3.0) | 10.5 | 164 (3.5) | 12.3 | 1.18 (”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Cardiovascular Outcomes · p. 4

    Empagliflozin was noninferior to placebo for the primary outcome (P<0.001 for noninferiority).

    “P<0.001 for noninferiority”
    Quote in the paperSubstantial claim
  • Findingown data
    § Cardiovascular Outcomes · p. 6

    A sensitivity analysis assuming all patients lost to follow-up in the empagliflozin group died and all in the placebo group were alive showed a significant benefit of empagliflozin versus placebo for death from any cause (HR 0.77; 95% CI 0.65-0.93; P=0.005).

    “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).”
    Quote in the paperNot a substantial claim
    • 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.
  • Findingown data
    § Cardiovascular Outcomes · p. 6

    In subgroup analyses, there was some heterogeneity for the primary outcome.

    “In subgroup analyses, there was some heterogeneity for the primary outcome.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 16
  • The quote only partly states this claim. 4
  • May combine two claims. 20

  • Classified as probably not a substantial claim.

    Premisecitation
    § ABSTRACT · p. 2

    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.

    “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”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • The quote only partly states this claim.

    Findingown data
    § Safety and Adverse Events · p. 7

    Genital infection was reported in a higher percentage of patients in the pooled empagliflozin group than in the placebo group.

    “Genital infection was reported in a higher percentage of patients in the pooled empagliflozin group.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Cardiovascular Risk Factors · p. 7

    A higher percentage of patients in the placebo group received additional glucose-lowering medications, antihypertensive medications, and anticoagulants during the trial, with no between-group difference in the receipt of lipid-lowering drugs.

    “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”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Cardiovascular Risk Factors · p. 7

    Over the course of the study, empagliflozin, 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.

    “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”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Glycemic Control · p. 7

    At week 206, adjusted mean differences in glycated hemoglobin between empagliflozin and placebo were -0.24 percentage points (95% CI -0.40 to -0.08) and -0.36 percentage points (95% CI -0.51 to -0.20) for the 10-mg and 25-mg groups, respectively.

    “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).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Cardiovascular Outcomes · p. 4

    Myocardial infarction was reported in 4.8% of empagliflozin patients and 5.4% of placebo patients, and stroke in 3.5% and 3.0%, respectively.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Safety and Adverse Events · p. 7

    Urosepsis was reported in 0.4% of patients in the empagliflozin group and 0.1% of those in the placebo group, with no imbalance in overall rates of urinary tract infection, complicated urinary tract infection, or pyelonephritis.

    “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”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Glycemic Control · p. 7

    After 12 weeks, empagliflozin reduced adjusted mean glycated hemoglobin compared with placebo by -0.54 percentage points (95% CI -0.58 to -0.49) in the 10-mg group and by -0.60 percentage points (95% CI -0.64 to -0.55) in the 25-mg group.

    “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”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data
    § RESULTS · p. 1

    Death from any cause occurred in 5.7% of empagliflozin patients and 8.3% of placebo patients (HR 0.68; 95% CI 0.57 to 0.82; P<0.001; 32% relative risk reduction).

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Safety and Adverse Events · p. 7

    The proportions of patients who had adverse events, serious adverse events, and adverse events leading to discontinuation of a study drug were similar in the empagliflozin group and the placebo group.

    “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”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Figure 2 (facing page). Subgroup Analyses for the Primary Outcome and Death from Cardiovascular Causes. · p. 11

    The proportions of patients with diabetic ketoacidosis, volume depletion, thromboembolic events, and bone fracture were low and similar in the empagliflozin groups and the placebo group.

    “The proportions of patients with diabetic ketoacidosis, volume depletion, thromboembolic events, and bone fracture were low (ranging from &lt;1% for ketoacidosis and thromboembolic events to 5% for volume depletion) and similar in the empagliflozin groups and the placebo group.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § RESULTS · p. 1

    Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events.

    “Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § RESULTS · p. 1

    There were no significant between-group differences in the rates of myocardial infarction or stroke.

    “There were no significant between-group differences in the rates of myocardial infarction or stroke”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data
    § RESULTS · p. 1

    Death from cardiovascular causes occurred in 3.7% of empagliflozin patients and 5.9% of placebo patients (HR 0.62; 95% CI 0.49 to 0.77; P<0.001; 38% relative risk reduction).

    “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)”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data
    § Safety and Adverse Events · p. 7

    Hematocrit values were higher in the empagliflozin groups than in the placebo group.

    “Hematocrit values were higher in the empagliflozin groups than in the placebo group”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Safety and Adverse Events · p. 7

    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.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Figure 2 (facing page). Subgroup Analyses for the Primary Outcome and Death from Cardiovascular Causes. · p. 11

    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.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Cardiovascular Outcomes · p. 4

    For the primary outcome, the hazard ratio was 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.

    “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.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data
    § RESULTS · p. 1

    Hospitalization for heart failure occurred in 2.7% of empagliflozin patients and 4.1% of placebo patients (HR 0.65; 95% CI 0.50 to 0.85; P=0.002; 35% relative risk reduction).

    “hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction)”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data
    § Cardiovascular Outcomes · p. 6

    In that sensitivity analysis, the point estimate for the hazard ratio for stroke was closer to 1.00.

    “and the point estimate for the hazard ratio for stroke was closer to 1.00”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Cardiovascular Outcomes · p. 4

    For the primary and key secondary outcomes, hazard ratios for the 10-mg dose 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.

    “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”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § ABSTRACT · p. 2

    There is concern that intensive glucose lowering or the use of specific glucose-lowering drugs may be associated with adverse cardiovascular outcomes.

    “there is concern that intensive glucose lowering or the use of specific glucose-lowering drugs may be associated with adverse cardiovascular outcomes. 8”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § ABSTRACT · p. 2

    Empagliflozin is a selective inhibitor of sodium glucose cotransporter 2.

    “Empagliflozin is a selective inhibitor of sodium glucose cotransporter 2 11”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] source

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data
    § Study Procedures · p. 3

    Randomization was performed with a computer-generated random-sequence and interactive voice- and Web-response system and was stratified according to glycated hemoglobin level, body-mass index, renal function, and geographic region.

    “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”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data
    § Statistical Analysis · p. 4

    The primary analysis used a modified intention-to-treat approach among patients who had received at least one dose of a study drug.

    “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.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationnone given
    § Figure 2 (facing page). Subgroup Analyses for the Primary Outcome and Death from Cardiovascular Causes. · p. 9

    These numbers cannot be extrapolated to patient populations with other clinical characteristics.

    “but these numbers cannot be extrapolated to patient populations with other clinical characteristics.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation
    § Study Oversight · p. 2

    Cardiovascular outcome events and deaths were prospectively adjudicated by two clinical-events committees.

    “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”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data
    § Study Patients · p. 4

    The median duration of treatment was 2.6 years and the median observation time was 3.1 years, similar in the pooled empagliflozin group and the placebo group.

    “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”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Study Oversight · p. 2

    An independent statistical analysis of cardiovascular outcomes was conducted by members of the University of Freiburg.

    “Members of the University of Freiburg conducted an independent statistical analysis of cardiovascular outcomes”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given
    § Study Oversight · p. 2

    The trial was conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice guidelines and was approved by local authorities and ethics committees.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data
    § Study Design · p. 2

    The trial was randomized, double-blind, and placebo-controlled.

    “this was a randomized, double-blind, placebo-controlled trial”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data
    § Figure 2 (facing page). Subgroup Analyses for the Primary Outcome and Death from Cardiovascular Causes. · p. 11

    The trial provides data to support the long-term use of empagliflozin and strong evidence for a reduction in cardiovascular risk.

    “Our trial provides data to support the longterm use of empagliflozin, as well as strong evidence for a reduction in cardiovascular risk.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data
    § Study Patients · p. 4

    Overall, 97.0% of patients completed the study, with 25.4% of patients prematurely discontinuing a study drug, and final vital status was available for 99.2% of patients.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § Study Oversight · p. 2

    Safety data were reviewed by an independent academic data monitoring committee every 90 days or at the discretion of the committee.

    “Safety data were reviewed by an independent academic data monitoring committee every 90 days or at the discretion of the committee.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § Study Design · p. 2

    The trial continued until an adjudicated primary outcome event had occurred in at least 691 patients.

    “The trial continued until an adjudicated primary outcome event had occurred in at least 691 patients.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given
    § Statistical Analysis · p. 3

    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.

    “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.”
    Quote in the paperSubstantial claim
36 of 36

  • 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”
2 of 2

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?

  • Canagliflozin reduced the risk of reduction in eGFR, ESKD, or death from ESKD by 40%.

    “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]

    The Results (p. 1) identify empagliflozin, not canagliflozin, as the treatment studied and report reductions in cardiovascular death, heart-failure hospitalization, and all-cause death—not a 40% reduction in the claimed kidney composite. The discussion (p. 11) says renal function was maintained with empagliflozin, but does not report the claimed outcome or percentage. (LLM, conf=0.88)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • Black Americans were underrepresented in the canagliflozin trial, comprising only 3.3% of all participants, and the trend towards greater amputations was not found in subsequent analyses.

    “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]

    Study Procedures (p. 3) identifies this as a trial of empagliflozin versus placebo, not a canagliflozin trial. Safety and Adverse Events (p. 7) does not report an amputation trend or subsequent analyses, and a search for 3.3% found no matching passage. (LLM, conf=0.85)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • In the EMPA-REG OUTCOME trial, the time to benefit emerged earlier than in the present trial.

    “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]

    The discussion on p. 9 says that reductions in cardiovascular and all-cause death occurred early in EMPA-REG OUTCOME and continued throughout the study. It does not compare the time to benefit with that of the citing authors’ present trial, so the ‘earlier than’ comparison is not supported by this source alone. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • SGLT2is and GLP-1RAs have demonstrated benefits in preventing deleterious cardiorenal endpoints among individuals with type 2 diabetes.

    “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]

    The Results (p. 1) show that empagliflozin, an SGLT2 inhibitor, reduced cardiovascular events in patients with type 2 diabetes at high cardiovascular risk. The discussion (p. 11) reports fewer acute renal-failure events and maintained renal function, but this trial does not establish broad cardiorenal benefits across SGLT2 inhibitors or evaluate GLP-1RAs. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Empagliflozin reduced the risk of doubling of serum creatinine accompanied by eGFR ≤45 mL/min/1.73m2 by 44%.

    “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]

    The discussion (p. 11) says renal function was maintained with empagliflozin and that acute renal failure was less frequent than with placebo. Our copy does not report a 44% reduction in doubling of serum creatinine accompanied by eGFR ≤45 mL/min/1.73 m²; searches for that endpoint and figure found no matching result. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Rosenstock J, 2015, Diabetes Obes Metab
  2. Chilton RC, 2014, Diabetes Obes Metab

Cited by

Sorted by citations

Related

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
DOI
10.1056/nejmoa1504720
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 · 2014: 6 · 2013: 2 · 2012: 2
FWCI
567.12
Type
journal article
Language
en
Open access
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

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-16.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-16.

Cited sources are checked by 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