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Cited by 708Diabetes Treatment and ManagementHeart Failure Treatment and ManagementCardiovascular Function and Risk Factors

Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology

Open access
Seferović, Petar M., Petrie, Mark C., Filippatos, Gerasimos S., Anker, Stefan D., Rosano, Giuseppe, Bauersachs, Johann, Paulus, Walter J., Komajda, Michel +25 more·2018·European Journal of Heart Failure
DOI 10.1002/ejhf.1170
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Abstract

The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30–40% of patients) and associated with a higher risk of HF hospitalization, all-cause and cardiovascular (CV) mortality. The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium. T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both disorders in the clinical practice. There are no specific limitations to HF treatment in T2DM. Subanalyses of trials addressing HF treatment in the general population have shown that all HF therapies are similarly effective regardless of T2DM. Concerning T2DM treatment in HF patients, most guidelines currently recommend metformin as the first-line choice. Sulphonylureas and insulin have been the traditional second- and third-line therapies although their safety in HF is equivocal. Neither glucagon-like preptide-1 (GLP-1) receptor agonists, nor dipeptidyl peptidase-4 (DPP4) inhibitors reduce the risk for HF hospitalization. Indeed, a DPP4 inhibitor, saxagliptin, has been associated with a higher risk of HF hospitalization. Thiazolidinediones (pioglitazone and rosiglitazone) are contraindicated in patients with (or at risk of) HF. In recent trials, sodium–glucose co-transporter-2 (SGLT2) inhibitors, empagliflozin and canagliflozin, have both shown a significant reduction in HF hospitalization in patients with established CV disease or at risk of CV disease. Several ongoing trials should provide an insight into the effectiveness of SGLT2 inhibitors in patients with HFrEF and HFpEF in the absence of T2DM.

AI snapshot

Written from the paper’s full text.

TL;DR

This Heart Failure Association of the European Society of Cardiology position statement reviews the frequent coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), its adverse prognostic impact, and current treatment implications. It concludes that standard HF therapies are similarly effective in patients with and without T2DM, that some glucose-lowering drugs increase HF risk, and that SGLT2 inhibitors reduce HF hospitalization while dedicated HF trials are ongoing.

Key findings

  • T2DM is common in HF: 30–40% of patients overall, around 30% in chronic HF trials irrespective of HFrEF/HFpEF, around 40% in acute HF trials, and 40–45% in hospitalized HF registries. A meta-analysis of 381,725 patients with acute and chronic HF found T2DM independently associated with higher all-cause death (HR 1.28), CV death (HR 1.34), hospitalization (HR 1.35), and all-cause death or hospitalization (HR 1.41).
  • Incident HF is a major complication of T2DM: in 1.9 million patients with T2DM without overt CV disease followed for 5.5 years, incident HF occurred in 14.1%, more frequently than MI or stroke. T2DM was associated with HF incidence rate 30.9 vs. 12.4/1000 person-years (rate ratio 2.5), and in UKPDS HF incidence rose from 2.3 to 11.9/1000 person-years for HbA1c <6% vs. >10%.
  • HF therapies including ACE inhibitors, ARBs, beta-blockers, mineralocorticoid receptor antagonists, sacubitril/valsartan, ivabradine, ICD/CRT-D, CABG, and exercise training were similarly effective in patients with and without T2DM. However, patients with T2DM had double the risk of hyperkalaemia on candesartan, and renal function/potassium monitoring is recommended with ACE inhibitors/ARBs and MRAs.
  • Among glucose-lowering drugs, thiazolidinediones (rosiglitazone, pioglitazone) and saxagliptin increase HF hospitalization (saxagliptin HR 1.27, P=0.007) and are contraindicated in patients with HF or at risk of HF. SGLT2 inhibitors reduced HF hospitalization in CV outcome trials: empagliflozin HR 0.65 and canagliflozin HR 0.67; canagliflozin was associated with higher lower-limb amputation risk (6.3 vs. 3.4 per 1000 patient-years; HR 1.97). GLP-1 receptor agonists and sitagliptin had neutral effects on HF hospitalization.

Methods

  • Design: position statement/clinical consensus document from the Heart Failure Association of the European Society of Cardiology, providing advice and education on clinical management of patients with T2DM and HF.
  • Data: narrative synthesis of population-based studies, registries, randomized clinical trials, and meta-analyses, including tables of T2DM prevalence in HF, mortality risk, antidiabetic drug HF outcomes, and ongoing SGLT2 inhibitor HF trials.
  • Analysis: descriptive review and interpretation of existing evidence; no new primary data collection or formal systematic review/meta-analysis by the authors is reported.

Limitations

  • The paper states that there are no clinical trials of HF treatment that included only patients with T2DM, so available evidence comes from subanalyses of mixed populations; there are also no RCTs in HF for metformin, insulin, sulphonylureas, or GLP-1 receptor agonists, and no accepted definition of diabetic cardiomyopathy.
  • The paper notes marked regional variation in T2DM prevalence among HF patients and states that reasons for this warrant further international studies with shared study design and standardized data collection.
  • Evident from the text: this is a position statement rather than a systematic review, many conclusions rely on observational data and subgroup analyses, and several key trials of SGLT2 inhibitors in HF (e.g., EMPEROR-Reduced, EMPEROR-Preserved, Dapa-HF) were ongoing and not yet available.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1002/ejhf.1170

Cites

193 of 193 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 257 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    The coexistence of T2DM and HF is associated with a higher risk of HF hospitalization.

    “The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients) and associated with a higher risk of HF hospitalization, all-cause and cardiovascular (CV) mortality.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [1] MacDonald, 2008, Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme, Eur Heart J source

      Not checked in the free run.

    • cites [93] Dauriz, 2017, Prognostic impact of diabetes on long-term survival outcomes in patients with heart failure: a meta-analysis, Diabetes Care source

      Not checked in the free run.

  • Premisecitation

    The coexistence of type 2 diabetes mellitus and heart failure, either with reduced or preserved ejection fraction, is frequent, affecting 30-40% of patients.

    “The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients)”
    Quote in the paperNot a substantial claim0 of 10 sources checked
    • cites [31] McMurray, 2014, PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure, N Engl J Med source

      Not checked in the free run.

    • cites [32] Swedberg, 2010, Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study, Lancet source

      Not checked in the free run.

    • cites [33] Ruschitzka, 2013, EchoCRT Study Group. Cardiac-resynchronization therapy in heart failure with a narrow QRS complex, N Engl J Med source

      Not checked in the free run.

    • cites [34] Banks, 2016, Response to exercise training and outcomes in patients with heart failure and diabetes mellitus: insights from the HF-ACTION trial, J Card Fail source

      Not checked in the free run.

    • cites [35] de Boer, 2010, Influence of diabetes mellitus and hyperglycemia on prognosis in patients ≥70 years old with heart failure and effects of nebivolol (data from the Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with heart failure [SENIORS]), Am J Cardiol source

      Not checked in the free run.

    • cites [36] Yusuf, 1991, Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure, N Engl J Med source

      Not checked in the free run.

    • cites [37] Deedwania, 2005, MERIT-HF Study Group. Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF, Am Heart J source

      Not checked in the free run.

    • cites [38] McMurray, 2003, CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial, Lancet source

      Not checked in the free run.

    • cites [39] Digitalis Investigation Group, 1997, The effect of digoxin on mortality and morbidity in patients with heart failure, N Engl J Med source

      Not checked in the free run.

    • cites [40] Kristensen, 2017, Clinical and echocardiographic characteristics and cardiovascular outcomes according to diabetes status in patients with heart failure and preserved ejection fraction: a report from the I-Preserve Trial (Irbesartan in Heart Failure With Preserved Ejection Fraction), Circulation source

      Not checked in the free run.

  • Premisecitation

    The coexistence of T2DM and HF is associated with a higher risk of all-cause mortality.

    “The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients) and associated with a higher risk of HF hospitalization, all-cause and cardiovascular (CV) mortality.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [1] MacDonald, 2008, Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme, Eur Heart J source

      Not checked in the free run.

    • cites [93] Dauriz, 2017, Prognostic impact of diabetes on long-term survival outcomes in patients with heart failure: a meta-analysis, Diabetes Care source

      Not checked in the free run.

  • Premisecitation

    In the EMPHASIS-HF trial including HFrEF patients, the incidence of T2DM was 3.7% over a median follow-up of 21 months.

    “In the EMPHASIS-HF trial including HFrEF patients, the incidence of T2DM was 3.7% over a median follow-up of 21 months.57”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Preiss, 2012, Eplerenone and new-onset diabetes in patients with mild heart failure: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF), Eur J Heart Fail source

      Not checked in the free run.

  • Premisecitation

    The severity of HF was associated with a stepwise increased risk of developing T2DM.

    “and the severity of HF was associated with a stepwise increased risk of developing T2DM.54”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Demant, 2014, Association of heart failure severity with risk of diabetes: a Danish nationwide cohort study, Diabetologia source

      Not checked in the free run.

  • May combine two claims. 41
  • Classified as probably not a substantial claim. 12

  • May combine two claims.

    Premisecitation

    T2DM is often unrecognized in HF patients, and vice versa.

    “T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [69] Kristensen, 2016, PARADIGM-HF Investigators and Committees. Risk related to pre-diabetes mellitus and diabetes mellitus in heart failure with reduced ejection fraction: insights from Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial, Circ Heart Fail source

      Not checked in the free run.

    • cites [73] Dauriz, 2017, Association between diabetes and 1-year adverse clinical outcomes in a multinational cohort of ambulatory patients with chronic heart failure: results from the ESC-HFA Heart Failure Long-Term Registry, Diabetes Care source

      Not checked in the free run.

    • cites [108] Kristensen, 2017, CHARM Investigators and Committees. Prevalence of prediabetes and undiagnosed diabetes in patients with HFpEF and HFrEF and associated clinical outcomes, Cardiovasc Drugs Ther source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    T2DM is associated with worse clinical status and increased all-cause and cardiovascular mortality in both HFrEF and HFpEF compared to HF patients without T2DM.

    “T2DM is associated with worse clinical status and increased all-cause and cardiovascular (CV) mortality in both patients with HF with reduced (HFrEF) and preserved ejection fraction (HFpEF), compared to HF patients without T2DM. 1”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] MacDonald, 2008, Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme, Eur Heart J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The major causes of HF in T2DM include coronary artery disease and hypertension, but also a possible direct detrimental effect of T2DM on the myocardium.

    “The major causes of HF in T2DM include coronary artery disease (CAD) and hypertension, but also, a possible direct detrimental effect of T2DM on the myocardium.4”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Seferovic, 2015, Clinical diabetic cardiomyopathy: a two-faced disease with restrictive and dilated phenotypes, Eur Heart J source

      Not checked in the free run.

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

    Premisecitation

    Approximately 25% of patients with HF in England and Denmark also had T2DM.

    “Approximately 25% of patients with HF in England 25 and Denmark 28 also had T2DM.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [25] Davies, 2001, Prevalence of left-ventricular systolic dysfunction and heart failure in the Echocardiographic Heart of England Screening study: a population based study, Lancet source

      Not checked in the free run.

    • cites [28] Kistorp, 2005, Prevalence and characteristics of diabetic patients in a chronic heart failure population, Int J Cardiol source

      Not checked in the free run.

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

    Premisecitation

    In the Swedish HF Registry, T2DM was more prevalent in HF patients with CAD compared to those without (30% vs. 19%).

    “In the Swedish HF Registry (68% from hospitals and 32% from primary care), T2DM was more prevalent in HF patients with CAD compared to those without (30% vs. 19%).53”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [53] Johansson, 2015, Risk factors, treatment and prognosis in men and women with heart failure with and without diabetes, Heart source

      Not checked in the free run.

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

    Premisecitation

    A slight increase in T2DM prevalence was reported in North America over time.

    “and a slight increase in the prevalence was reported in North America over time.49,52”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [49] Echouffo-Tcheugui, 2016, Temporal trends and factors associated with diabetes mellitus among patients hospitalized with heart failure: findings from Get With The Guidelines-Heart Failure registry, Am Heart J source

      Not checked in the free run.

    • cites [52] Win, 2016, Mortality among patients hospitalized with heart failure and diabetes mellitus: results from the National Inpatient Sample 2000 to 2010, Circ Heart Fail source

      Not checked in the free run.

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

    Premisecitation

    In registries of hospitalized HF patients in North America and Europe, the prevalence of T2DM is around 40-45%.

    “In registries of hospitalized HF patients in North America and Europe, the prevalence of T2DM is around 40-45%, 49 -52”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [49] Echouffo-Tcheugui, 2016, Temporal trends and factors associated with diabetes mellitus among patients hospitalized with heart failure: findings from Get With The Guidelines-Heart Failure registry, Am Heart J source

      Not checked in the free run.

    • cites [50] Sud, 2017, Associations between short or long length of stay and 30-day readmission and mortality in hospitalized patients with heart failure, JACC Heart Fail source

      Not checked in the free run.

    • cites [51] Targher, 2017, ESC-HFA HF Long-Term Registry Investigators. In-hospital and 1-year mortality associated with diabetes in patients with acute heart failure: results from the ESC-HFA Heart Failure Long-Term Registry, Eur J Heart Fail source

      Not checked in the free run.

    • cites [52] Win, 2016, Mortality among patients hospitalized with heart failure and diabetes mellitus: results from the National Inpatient Sample 2000 to 2010, Circ Heart Fail source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The most important causes of HF in T2DM are coronary artery disease, arterial hypertension, and a direct detrimental effect of T2DM on the myocardium.

    “The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Seferovic, 2015, Clinical diabetic cardiomyopathy: a two-faced disease with restrictive and dilated phenotypes, Eur Heart J source

      Not checked in the free run.

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

    Premisecitation

    The highest prevalence of T2DM was seen in trials of acute HF, around 40%.

    “The highest prevalence of T2DM was seen in trials of acute HF (around 40%).”
    Quote in the paperNot a substantial claim0 of 10 sources checked
    • cites [31] McMurray, 2014, PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure, N Engl J Med source

      Not checked in the free run.

    • cites [32] Swedberg, 2010, Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study, Lancet source

      Not checked in the free run.

    • cites [33] Ruschitzka, 2013, EchoCRT Study Group. Cardiac-resynchronization therapy in heart failure with a narrow QRS complex, N Engl J Med source

      Not checked in the free run.

    • cites [34] Banks, 2016, Response to exercise training and outcomes in patients with heart failure and diabetes mellitus: insights from the HF-ACTION trial, J Card Fail source

      Not checked in the free run.

    • cites [35] de Boer, 2010, Influence of diabetes mellitus and hyperglycemia on prognosis in patients ≥70 years old with heart failure and effects of nebivolol (data from the Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with heart failure [SENIORS]), Am J Cardiol source

      Not checked in the free run.

    • cites [36] Yusuf, 1991, Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure, N Engl J Med source

      Not checked in the free run.

    • cites [37] Deedwania, 2005, MERIT-HF Study Group. Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF, Am Heart J source

      Not checked in the free run.

    • cites [38] McMurray, 2003, CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial, Lancet source

      Not checked in the free run.

    • cites [39] Digitalis Investigation Group, 1997, The effect of digoxin on mortality and morbidity in patients with heart failure, N Engl J Med source

      Not checked in the free run.

    • cites [40] Kristensen, 2017, Clinical and echocardiographic characteristics and cardiovascular outcomes according to diabetes status in patients with heart failure and preserved ejection fraction: a report from the I-Preserve Trial (Irbesartan in Heart Failure With Preserved Ejection Fraction), Circulation source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the SOLVD-Prevention trial, patients with T2DM were more likely to progress to symptomatic HF than those without T2DM, although the increased risk appeared to be confined to patients with HF secondary to CAD.

    “In the SOLVD-Prevention trial of patients with asymptomatic left ventricular systolic dysfunction, patients with T2DM were more likely to progress to symptomatic HF than those without T2DM, although the increased risk appeared to be confined to patients with HF secondary to CAD. 71”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [71] Das, 2004, Effects of diabetes mellitus and ischemic heart disease on the progression from asymptomatic left ventricular dysfunction to symptomatic heart failure: a retrospective analysis from the Studies of Left Ventricular Dysfunction (SOLVD) Prevention trial, Am Heart J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Clinical trial results are somewhat conflicting regarding the risk of all-cause and cardiovascular mortality attributed to T2DM in HF patients, but most clinical trials reported an increased risk of death in patients with concurrent T2DM and HF.

    “Clinical trial results are somewhat conflicting regarding the risk of all-cause and CV mortality attributed to T2DM in HF patients, but most clinical trials reported an increased risk of death in patients with concurrent T2DM and HF (Table 5).1,31 -35,37,40,42,44,45,69,88-92”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [1] MacDonald, 2008, Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme, Eur Heart J source

      Not checked in the free run.

    • cites [31] McMurray, 2014, PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure, N Engl J Med source

      Not checked in the free run.

    • cites [32] Swedberg, 2010, Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study, Lancet source

      Not checked in the free run.

    • cites [33] Ruschitzka, 2013, EchoCRT Study Group. Cardiac-resynchronization therapy in heart failure with a narrow QRS complex, N Engl J Med source

      Not checked in the free run.

    • cites [34] Banks, 2016, Response to exercise training and outcomes in patients with heart failure and diabetes mellitus: insights from the HF-ACTION trial, J Card Fail source

      Not checked in the free run.

    • cites [35] de Boer, 2010, Influence of diabetes mellitus and hyperglycemia on prognosis in patients ≥70 years old with heart failure and effects of nebivolol (data from the Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with heart failure [SENIORS]), Am J Cardiol source

      Not checked in the free run.

    • cites [37] Deedwania, 2005, MERIT-HF Study Group. Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF, Am Heart J source

      Not checked in the free run.

    • cites [40] Kristensen, 2017, Clinical and echocardiographic characteristics and cardiovascular outcomes according to diabetes status in patients with heart failure and preserved ejection fraction: a report from the I-Preserve Trial (Irbesartan in Heart Failure With Preserved Ejection Fraction), Circulation source

      Not checked in the free run.

    • cites [42] Ahmed, 2006, Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary Digitalis Investigation Group trial, Circulation source

      Not checked in the free run.

    • cites [44] Pitt, 2014, Spironolactone for heart failure with preserved ejection fraction, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Patients with T2DM and HFrEF have shorter 6-minute walk distances and decreased peak oxygen uptake compared to non-diabetics.

    “Patients with T2DM and HFrEF also have shorter 6-minute walk distances and decreased peak oxygen uptake in comparison to non-diabetics.55,69,72”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [55] Ingle, 2006, Diabetes lowers six-minute walk test performance in heart failure, J Am Coll Cardiol source

      Not checked in the free run.

    • cites [69] Kristensen, 2016, PARADIGM-HF Investigators and Committees. Risk related to pre-diabetes mellitus and diabetes mellitus in heart failure with reduced ejection fraction: insights from Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial, Circ Heart Fail source

      Not checked in the free run.

    • cites [72] Egstrup, 2013, Abnormal glucose metabolism is associated with reduced left ventricular contractile reserve and exercise intolerance in patients with chronic heart failure, Eur Heart J Cardiovasc Imaging source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The incidence of HF in T2DM patients compared to those without T2DM is even higher in patients with established CAD, in which each 1% increase in HbA1c level was associated with a 36% increased risk for HF hospitalization.

    “The incidence of HF in T2DM patients compared to those without T2DM is even higher in patients with established CAD, in which each 1% increase in HbA 1c level was associated with a 36% increased risk for HF hospitalization.66,67”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [66] Bibbins-Domingo, 2004, Predictors of heart failure among women with coronary disease, Circulation source

      Not checked in the free run.

    • cites [67] van Melle, 2010, Diabetes, glycemic control, and new-onset heart failure in patients with stable coronary artery disease: data from the Heart and Soul Study, Diabetes Care source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In two population-based studies from Scotland and Sweden, the increased mortality risk of T2DM was seen in both women and men, but the effect was slightly greater in women.

    “In two population-based studies from Scotland and Sweden, the increased mortality risk of T2DM was seen in both women and men, but the effect was slightly greater in women.87,96”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [87] MacDonald, 2008, Discordant short- and long-term outcomes associated with diabetes in patients with heart failure: importance of age and sex: a population study of 5.1 million people in Scotland, Circ Heart Fail source

      Not checked in the free run.

    • cites [96] Andersson, 2010, Long-term impact of diabetes in patients hospitalized with ischemic and non-ischemic heart failure, Scand Cardiovasc J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A recent meta-analysis of 31 registries and 12 clinical trials with 381,725 patients with acute and chronic HF, with a median follow-up of 3 years, confirms that T2DM is independently associated with a higher risk of all-cause death (random-effects HR 1.28), cardiovascular death (HR 1.34), hospitalization (HR 1.35), and the combined endpoint of all-cause death or hospitalization (HR 1.41).

    “A recent meta-analysis of 31 registries and 12 clinical trials with 381 725 patients with acute and chronic HF, with a median follow-up of 3 years confirms that T2DM is independently associated with a higher risk of all-cause death (random-effects HR 1.28), CV death (HR 1.34), hospitalization (HR 1.35), and the combined endpoint of all-cause death or hospitalization (HR 1.41)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [93] Dauriz, 2017, Prognostic impact of diabetes on long-term survival outcomes in patients with heart failure: a meta-analysis, Diabetes Care source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Concerning HFpEF, all trials reported increased all-cause mortality (HRs 1.5 to 1.8) and two out of four trials also reported an increased risk of cardiovascular mortality in patients with T2DM compared to patients without T2DM, with HRs 1.6 to 1.9.

    “Concerning HFpEF, all trials reported increased all-cause mortality (HRs 1.5 to 1.8) and two out of four trials also reported an increased risk of CV mortality in patients with T2DM compared to patients without T2DM, with HRs 1.6 to 1.9 (Table 5).”
    Quote in the paperSubstantial claim

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

    Premisecitation

    An early report from the Framingham study reported that the mortality risk related to T2DM was confined to women and not to men.

    “An early report from the Framingham study reported that the mortality risk related to T2DM was confined to women and not to men.103”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [103] Kannel, 1974, Role of diabetes in congestive heart failure: the Framingham study, Am J Cardiol source

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

    Premisecitation

    A 50-year-old with T2DM died, on average, 6 years earlier than an individual without T2DM, with about 40% of the difference in survival attributable to excess non-vascular deaths.

    “The study found that a 50-year-old with T2DM died, on average, 6 years earlier than an individual without T2DM, with about 40% of the difference in survival attributable to excess non-vascular deaths.95”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [95] Rao Kondapally Seshasai, 2011, Diabetes mellitus, fasting glucose, and risk of cause-specific death, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the GISSI-HF study, including 6935 chronic HF patients, the presence of T2DM and higher HbA1c levels was an independent predictor of all-cause mortality (HRs 1.43 and 1.21, respectively) and the composite outcome of mortality and cardiovascular hospitalization (HRs 1.21 and 1.14, respectively).

    “In the GISSI-HF study, including 6935 chronic HF patients, the presence of T2DM and higher HbA 1c levels was an independent predictor of all-cause mortality (HRs 1.43 and 1.21, respectively) and the composite outcome of mortality and CV hospitalization (HRs 1.21 and 1.14, respectively).107”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [107] Dauriz, 2017, Prognostic impact of diabetes and prediabetes on survival outcomes in patients with chronic heart failure: a post-hoc analysis of the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) Trial, J Am Heart Assoc source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Three HFrEF trials reported increased cardiovascular death, with hazard ratios between 1.5 and 1.8.

    “Also three HFrEF trials reported increased CV death, with HRs between 1.5 and 1.8.1,31,33”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [1] MacDonald, 2008, Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme, Eur Heart J source

      Not checked in the free run.

    • cites [31] McMurray, 2014, PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure, N Engl J Med source

      Not checked in the free run.

    • cites [33] Ruschitzka, 2013, EchoCRT Study Group. Cardiac-resynchronization therapy in heart failure with a narrow QRS complex, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the CHARM trial, T2DM was an independent risk factor for both all-cause mortality and cardiovascular mortality even after adjustment for 32 covariates.

    “In the CHARM trial, T2DM was an independent risk factor for both all-cause mortality and CV mortality even after adjustment for 32 covariates. 1”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] MacDonald, 2008, Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme, Eur Heart J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In HFrEF, five out of eight trials demonstrated an association between T2DM and increased all-cause mortality, with reported hazard ratios between 1.3 and 2.0 (mostly around 1.5).

    “In HFrEF, five out of eight trials demonstrated an association between T2DM and increased all-cause mortality, with the reported HRs between 1.3 and 2.0 (mostly around 1.5) (Table 5).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the recent ESC HF Long-Term Registry and in the CHARM trial, T2DM was a risk factor for mortality in both men and women.

    “Likewise, in the recent ESC HF Long-Term Registry and in the CHARM trial, T2DM was a risk factor for mortality in both men and women.1,73”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] MacDonald, 2008, Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme, Eur Heart J source

      Not checked in the free run.

    • cites [73] Dauriz, 2017, Association between diabetes and 1-year adverse clinical outcomes in a multinational cohort of ambulatory patients with chronic heart failure: results from the ESC-HFA Heart Failure Long-Term Registry, Diabetes Care source

      Not checked in the free run.

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

    Premisecitation

    Two smaller population-based studies in the United States and France and one Spanish single-centre study suggested that diabetes was only associated with higher mortality in those with non-ischaemic aetiology.

    “These consistent findings conflict with two smaller population-based studies in the United States 29 and France 97 and one Spanish single-centre study 101 of patients hospitalized with HF, which suggested that diabetes was only associated with higher mortality in those with non-ischaemic aetiology.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [29] From, 2006, Diabetes in heart failure: prevalence and impact on outcome in the population, Am J Med source

      Not checked in the free run.

    • cites [97] De Groote, 2004, Impact of diabetes mellitus on long-term survival in patients with congestive heart failure, Eur Heart J source

      Not checked in the free run.

    • cites [101] Varela-Roman, 2005, Influence of diabetes on the survival of patients hospitalized with heart failure: a 12-year study, Eur J Heart Fail source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The Emerging Risk Factors Collaboration, including 820,900 people, demonstrates that T2DM is independently associated with increased risk of death from several cancers, renal and liver disease, pneumonia and other infectious diseases, mental and nervous system disorders, non-hepatic digestive diseases, external causes, and chronic obstructive pulmonary disease.

    “Aside from CV death, results from the Emerging Risk Factors Collaboration, including 820 900 people, demonstrate that T2DM is independently associated with increased risk of death from several cancers (i.e.liver, pancreas, ovary, colorectum, lung, bladder, and breast), renal and liver disease, pneumonia and other infectious diseases, mental and nervous system disorders, non-hepatic digestive dis”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [95] Rao Kondapally Seshasai, 2011, Diabetes mellitus, fasting glucose, and risk of cause-specific death, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In patients from a US study of HF clinics, a U-shaped relationship with regard to increased all-cause mortality was found; patients with low or very high HbA1c were at greatest risk.

    “In patients from a US study of HF clinics, a U-shaped relationship with regard to increased all-cause mortality was found.71 or very high HbA 1c were at greatest risk.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [71] Das, 2004, Effects of diabetes mellitus and ischemic heart disease on the progression from asymptomatic left ventricular dysfunction to symptomatic heart failure: a retrospective analysis from the Studies of Left Ventricular Dysfunction (SOLVD) Prevention trial, Am Heart J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a large trial involving 6558 patients with HF (30% with T2DM), ivabradine demonstrated a significant reduction in the composite endpoint of CV death or HF hospitalization, with no difference between T2DM and non-T2DM patients (HRs 0.81 and 0.83, respectively).

    “In a large trial involving 6558 patients with HF (30% with T2DM), ivabradine demonstrated a significant reduction in the composite endpoint of CV death or HF hospitalization, with no difference between T2DM and non-T2DM patients (HRs 0.81 and 0.83, respectively).164”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [164] Komajda, 2015, Efficacy and safety of ivabradine in patients with chronic systolic heart failure and diabetes: an analysis from the SHIFT trial, Eur J Heart Fail source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Diabetic nephropathy is characterized by increased renal sodium retention and a higher risk of hyperkalaemia.

    “Specifically, diabetic nephropathy is characterized by increased renal sodium retention 149,150 and a higher risk of hyperkalaemia.151”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [149] de Chatel, 1977, Sodium, renin, aldosterone, catecholamines, and blood pressure in diabetes mellitus, Kidney Int source

      Not checked in the free run.

    • cites [150] Anderson, 1993, Renal renin-angiotensin system in diabetes: functional, immunohistochemical, and molecular biological correlations, Am J Physiol

      Not checked in the free run.

    • cites [151] DeFronzo, 1980, Hyperkalemia and hyporeninemic hypoaldosteronism, Kidney Int source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the CHARM trial, patients with T2DM experienced a significantly higher rate of SCD compared to patients without T2DM (40 vs. 25.9 events/1000 patient-years of follow-up), and the increased risk of SCD was observed irrespective of HF phenotype (i.e. HFrEF and HFpEF).

    “In the CHARM trial, patients with T2DM experienced a significantly higher rate of SCD compared to patients without T2DM (40 vs. 25.9 events/1000 patient-years of follow-up), and the increased risk of SCD was observed irrespective of HF phenotype (i.e.HFrEF and HFpEF). 1”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] MacDonald, 2008, Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme, Eur Heart J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    T2DM confers a higher risk of diabetic nephropathy and chronic kidney disease.

    “T2DM confers a higher risk of diabetic nephropathy and chronic kidney disease.148”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [148] Collins, 2010, Excerpts from the US Renal Data System 2009 Annual Data Report, Am J Kidney Dis source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Thus far, there were no clinical trials of HF treatment that included only patients with T2DM, and available evidence is derived from subanalyses of mixed populations.

    “Thus far, there were no clinical trials of HF treatment that included only patients with T2DM, and available evidence is derived from subanalyses of mixed populations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Eplerenone seems to have no effect on new-onset T2DM in patients with HF, suggesting a neutral metabolic profile.

    “Importantly, eplerenone seems to have no effect on new-onset T2DM in patients with HF, suggesting a neutral metabolic profile.160”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [160] Dei Cas, 2015, Impact of diabetes on epidemiology, treatment, and outcomes of patients with heart failure, JACC Heart Fail source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a meta-analysis of six trials, beta-blocker therapy reduced all-cause mortality in patients with T2DM (HR 0.84) similarly to those without T2DM (HR 0.72).

    “In a meta-analysis of six trials, beta-blocker therapy reduced all-cause mortality in patients with T2DM (HR 0.84) similarly to those without T2DM (HR 0.72).156”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [156] Haas, 2003, Are beta-blockers as efficacious in patients with diabetes mellitus as in patients without diabetes mellitus who have chronic heart failure? A meta-analysis of large-scale clinical trials, Am Heart J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ACE-inhibitors improve symptoms and reduce morbidity and mortality in patients with HFrEF and T2DM.

    “as they have been shown to improve symptoms and reduce morbidity and mortality.116”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [116] Ponikowski, 2016, 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC, Eur J Heart Fail source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    T2DM is associated with a two-fold higher risk of CAD and ischaemic stroke.

    “T2DM is associated with a two-fold higher risk of CAD and ischaemic stroke”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [139] Gu, 1998, Mortality in adults with and without diabetes in a national cohort of the U.S. population, 1971–1993, Diabetes Care source

      Not checked in the free run.

    • cites [140] Kannel, 1979, Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham study, Diabetes Care source

      Not checked in the free run.

    • cites [141] Lee, 2000, Impact of diabetes on coronary artery disease in women and men: a meta-analysis of prospective studies, Diabetes Care source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Patients with T2DM and HF are at increased risk of malignant ventricular arrhythmias and SCD.

    “In addition to a higher risk of death due to worsening HF, patients with T2DM and HF are at increased risk of malignant ventricular arrhythmias and SCD.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [1] MacDonald, 2008, Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme, Eur Heart J source

      Not checked in the free run.

    • cites [75] Cubbon, 2013, Diabetes mellitus is associated with adverse prognosis in chronic heart failure of ischaemic and non-ischaemic aetiology, Diabetes Vasc Dis Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the CHARM trial, candesartan achieved a significant reduction in CV death, HF hospitalization and all-cause mortality in patients with HF and HFrEF, irrespective of T2DM.

    “In the CHARM trial, a significant reduction in CV death, HF hospitalization and all-cause mortality was achieved with candesartan in patients with HF and HFrEF, irrespectively of T2DM. 1”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] MacDonald, 2008, Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme, Eur Heart J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Subgroup analyses of large HF trials show that beta-blockers reduce mortality and hospitalization and improve symptoms in moderate to severe HF, irrespective of T2DM.

    “Subgroup analyses of large HF trials show that beta-blockers reduce mortality and hospitalization and improve symptoms in moderate to severe HF, irrespectively of T2DM.37,152,153”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [37] Deedwania, 2005, MERIT-HF Study Group. Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF, Am Heart J source

      Not checked in the free run.

    • cites [152] Erdmann, 2001, Results from post-hoc analyses of the CIBIS II trial: effect of bisoprolol in high-risk patient groups with chronic heart failure, Eur J Heart Fail source

      Not checked in the free run.

    • cites [153] Packer, 2002, Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study Group. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study, Circulation source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ICD treatment led to a significant relative risk reduction in death and in subgroup analysis, there were no interactions with T2DM.

    “ICD treatment led to a significant relative risk reduction in death and in subgroup analysis, there were no interactions with T2DM.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [165] Bardy, 2005, Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Drugs that are now known to increase the risk for HF are thiazolidinediones (TZDs) and a dipeptidyl peptidase-4 (DPP4) inhibitor, saxagliptin.

    “Drugs that are now known to increase the risk for HF are thiazolidinediones (TZDs) and a dipeptidyl peptidase-4 (DPP4) inhibitor, saxagliptin.16,17”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [16] Scirica, 2015, Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial, Circulation

      Not checked in the free run.

    • cites [17] Scirica, 2013, SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The HF-ACTION trial enrolled 32% of patients with T2DM and there was no interaction between T2DM status and the effect of exercise on clinical outcomes.

    “The trial enrolled 32% of patients with T2DM and there was no interaction between T2DM status and the effect of exercise on clinical outcomes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Banks, 2016, Response to exercise training and outcomes in patients with heart failure and diabetes mellitus: insights from the HF-ACTION trial, J Card Fail source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    These studies, although large, are non-randomized and therefore inconclusive.

    “These studies, although large, are non-randomized and therefore inconclusive.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    HF treatment with medications and devices (e.g., ICD, CRT-D) is similarly effective in patients with and without T2DM.

    “HF treatment with medications and devices (e.g.ICD, CRT-D) is similarly effective in patients with and without T2DM.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Empagliflozin in EMPA-REG OUTCOME, but not canagliflozin in CANVAS, reduced all-cause and CV mortality as well as HF hospitalization.

    “Empagliflozin in EMPA-REG OUTCOME, but not canagliflozin in CANVAS, reduced all-cause and CV mortality as well as HF hospitalization.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [20] Zinman, 2015, Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes, N Engl J Med source

      Not checked in the free run.

    • cites [21] Neal, 2017, CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the LIVE trial, there was a significant increase in heart rate (P<0.0001) and more serious cardiac adverse events with liraglutide (P=0.04).

    “However, there was a significant increase in heart rate (P<0.0001) and more serious cardiac adverse events with liraglutide (P=0.04).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [180] Jorsal, 2017, Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE) – a multicentre, double-blind, randomised, placebo-controlled trial, Eur J Heart Fail source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    The causes of HF in T2DM are numerous, but CAD and hypertension are likely the most important contributors to concurrent T2DM and HF, whereas a direct effect of T2DM on the myocardium (e.g. 'diabetic cardiomyopathy') might also play a role.

    “The causes of HF in T2DM are numerous, but CAD and hypertension are likely the most important contributors to concurrent T2DM and HF, whereas a direct effect of T2DM on the myocardium (e.g.'diabetic cardiomyopathy') might also play a role.”
    Quote in the paperNot a substantial claim

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

    Premisenone given

    SGLT2 inhibitors are currently being investigated as a potential addition to optimal medical treatment of HF in patients with and without T2DM.

    “SGLT2 inhibitors are currently being investigated as a potential addition to the optimal medical treatment of HF, not only in patients with, but also in those without T2DM.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Type 2 diabetes mellitus and HF are both common and frequently co-exist.

    “Type 2 diabetes mellitus and HF are both common and frequently co-exist.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In the CANVAS trial, treatment with canagliflozin was associated with a significantly higher risk of lower-limb amputations (6.3 vs. 3.4 per 1000 patient-years; HR 1.97) and possibly a higher risk of fractures compared with placebo.

    “In the CANVAS trial, treatment with canagliflozin was associated with a significantly higher risk of lower-limb amputations (6.3 vs. 3.4 per 1000 patient-years; HR 1.97) and possibly a higher risk of fractures compared with placebo.21”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Neal, 2017, CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    In patients with heart failure (HF) and type 2 diabetes mellitus (T2DM), there is a significantly higher risk of adverse outcomes, including hospitalization and rehospitalization for HF, and increased all-cause and cardiovascular mortality, compared with patients with HF without T2DM, independent of HF aetiology or phenotype (HFrEF and HFpEF).

    “indicates a significantly higher risk of adverse outcomes in patients with HF and T2DM, including a higher risk for hospitalization and rehospitalization for HF, as well as increased all-cause and CV mortality, independent of HF aetiology or phenotype (i.e.HFrEF and HFpEF).”
    Quote in the paperSubstantial claim

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

    Premisenone given

    Bromocriptine has not been studied with respect to its effect on HF outcomes.

    “Bromocriptine has not been studied with respect to its effect on HF outcomes.”
    Quote in the paperNot a substantial claim
51 of 51

  • The paper relies on this without support.

    There is no definition of diabetic cardiomyopathy.

    “There is no definition of diabetic cardiomyopathy, which makes studies of epidemiology, pathophysiology, natural history and associated clinical outcomes challenging.”

  • The paper relies on this without support.

    Hypoglycaemia is a concern in patients with T2DM treated with insulin or sulfonylureas.

    “Hypoglycaemia is a concern in patients with T2DM treated with insulin or sulfonylureas.”

  • The paper relies on this without support.

    Diuretics are usually required to treat the symptoms and signs of fluid overload in patients with HF.

    “Diuretics are usually required to treat the symptoms and signs of fluid overload in patients with HF.”

  • The paper relies on this without support.

    Insulin causes sodium and water retention.

    “insulin, which causes sodium and water retention”

  • The paper relies on this without support.

    Sulphonylureas are insulin secretagogues.

    “sulphonylureas which, as insulin secretagogues”
5 of 5

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Italian prevalence ratio is not threefold

    Minor

    The listed Italian prevalences are 30% in patients with heart failure and 13% in the comparison population. Their ratio is about 2.31, not three.

    Reported 3 · recomputed 2.307692

  • Medicare mortality estimate lies outside its confidence interval

    Minor

    Table 4 gives the White-patient hazard ratio as 1.22, but its stated 95% confidence interval runs from 1.24 to 1.25 and therefore excludes the estimate.

  • HFrEF mortality hazard-ratio range omits EchoCRT

    Minor

    The stated upper end of 2.0 is below EchoCRT's reported all-cause mortality hazard ratio of 2.08.

  • French study shows the opposite aetiology-specific mortality pattern

    Minor

    The text groups the French study with studies finding higher mortality only in non-ischaemic heart failure. Table 6 instead reports a confidence interval above 1 for heart failure secondary to CAD and an interval crossing 1 for other aetiologies.

4 of 4

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Related

Authors
Seferović, P. M., Petrie, M. C., Filippatos, G. S., Anker, S. D., Rosano, G., Bauersachs, J., Paulus, W. J., Komajda, M., Cosentino, F., de Boer, R. A., Farmakis, D., Doehner, W., Lambrinou, E., Lopatin, Y., Piepoli, M. F., Theodorakis, M. J., Wiggers, H., Lekakis, J., Mebazaa, A., Mamas, M. A., Tschöpe, C., Hoes, A. W., Seferović, J. P., Logue, J., McDonagh, T., Riley, J. P., Milinković, I., Polovina, M., van Veldhuisen, D. J., Lainscak, M., Maggioni, A. P., Ruschitzka, F., & McMurray, J. J. V.
Affiliations
  • University of Belgrade School of Medicine, Belgrade University Medical Center , Belgrade ,
  • British Heart Foundation (GB)
  • National and Kapodistrian University of Athens (GR)
  • Universitätsmedizin Göttingen (DE)
  • St George's, University of London (GB)
  • Royal Brompton Hospital (GB)
  • Amsterdam Cardiovascular Sciences (NL)
  • Institute of Cardiometabolism and Nutrition (ICAN), Pierre et Marie Curie University, Paris VI, La Pitié-Salpétrière Hospital , Paris ,
  • Karolinska University Hospital (SE)
  • University of Groningen, University Medical Centre Groningen, Department of Cardiology, Hanzeplein Groningen
  • Center for Stroke Research Berlin (DE)
  • Cyprus University of Technology (CY)
  • Volgograd Medical University, Cardiology Centre , Volgograd ,
  • Azienda Unità Sanitaria Locale Piacenza (IT)
  • Aarhus University Hospital (DK)
  • Hôpital Lariboisière (FR)
  • Keele University (GB)
  • Charité – Universitätsmedizin Berlin (DE)
  • University Medical Center Utrecht (NL)
  • University of Belgrade (RS)
  • University of Glasgow (GB)
  • King's College Hospital (GB)
  • Imperial College London (GB)
  • Department of Cardiology, University Medical Center Groningen, University of Groningen , Groningen ,
  • Department of Internal Medicine, and Department of Research and Education, General Hospital Murska Sobota , Murska Sobota ,
  • Research Center of the Italian Association of Hospital Cardiologists , Florence ,
  • University Hospital Zurich (CH)
ORCID
Venue
European Journal of Heart Failure
Publisher
Oxford University Press (OUP)
Published
2018-03-08
Volume
20
Issue
5
Pages
853-872
ISSN
  • 1388-9842 (ISSN-L)
  • 1879-0844
DOI
10.1002/ejhf.1170
OpenAlex
W2793795908
Cited by
708
References
193
Citations by year
2026: 47 · 2025: 63 · 2024: 106 · 2023: 85 · 2022: 88 · 2021: 89 · 2020: 91 · 2019: 103 · 2018: 34
FWCI
63.02
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • European Journal of Heart Failure (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, cc-by)
  • St George's Online Research Archive (St George's University of London) (acceptedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
  • Research Bank (Australian Catholic University) (submittedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • Keele Research Repository (Keele University) (submittedVersion, cc-by)
  • Lancaster EPrints (Lancaster University) (submittedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion, other-oa)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Zurich Open Repository and Archive (University of Zurich)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords
type 2 diabetes, heart failure, heart failure with reduced ejection fraction, heart failure with preserved ejection fraction, heart failure hospitalization, cardiovascular mortality, metformin, sulfonylureas, insulin, GLP-1 receptor agonists, DPP-4 inhibitors, saxagliptin, thiazolidinediones, SGLT2 inhibitors, empagliflozin, canagliflozin, coronary artery disease, hypertension
MeSH terms
Cardiology, Diabetes Mellitus, Type 2, Europe, Heart Failure, Humans, Societies, Medical, Global Health, Comorbidity, Prevalence, Survival Rate

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 2026-10-10.

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

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