Type 2 Diabetes Mellitus and Heart Failure: A Position Statement from the Heart Failure Association of the European Society of Cardiology

In the paper

“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.”

What the sources say

• Not checked yetcites [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 yetcites [93] Dauriz, 2017, Prognostic impact of diabetes on long-term survival outcomes in patients with heart failure: a meta-analysis, Diabetes Care source

In the paper

“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)”

What the sources say

• Not checked yetcites [31] McMurray, 2014, PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure, N Engl J Med source
• Not checked yetcites [32] Swedberg, 2010, Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study, Lancet source
• Not checked yetcites [33] Ruschitzka, 2013, EchoCRT Study Group. Cardiac-resynchronization therapy in heart failure with a narrow QRS complex, N Engl J Med source
• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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 yetcites [93] Dauriz, 2017, Prognostic impact of diabetes on long-term survival outcomes in patients with heart failure: a meta-analysis, Diabetes Care source

In the paper

“In the EMPHASIS-HF trial including HFrEF patients, the incidence of T2DM was 3.7% over a median follow-up of 21 months.57”

What the sources say

• Not checked yetcites [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

In the paper

“and the severity of HF was associated with a stepwise increased risk of developing T2DM.54”

What the sources say

• Not checked yetcites [54] Demant, 2014, Association of heart failure severity with risk of diabetes: a Danish nationwide cohort study, Diabetologia source

In the paper

“Registry data corroborate that the use of renin-angiotensin system inhibitors is associated with attenuated risk for T2DM in HF patients receiving loop diuretics.54”

What the sources say

• Not checked yetcites [54] Demant, 2014, Association of heart failure severity with risk of diabetes: a Danish nationwide cohort study, Diabetologia source

In the paper

“In a Kaiser Permanente study, the incidence of T2DM was significantly higher in patients with than without HF (i.e.13.6/1000 vs. 9.2/1000) over a 5-year follow-up.10”

What the sources say

• Not checked yetcites [10] Nichols, 2001, Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors, Diabetes Care source

In the paper

“Despite younger age and less obesity, a significantly higher prevalence of T2DM (57%) was observed in a population-based cohort of Southeast Asian HF patients compared to Caucasian patients (24%).30”

What the sources say

• Not checked yetcites [30] Bank IE, 2017, Prevalence and clinical significance of diabetes in asian versus white patients with heart failure, JACC Heart Fail source

In the paper

“Clinical trials also demonstrated that the severity of HF, as indicated by a higher New York Heart Association (NYHA) class, increases the likelihood of developing T2DM.27,59”

What the sources say

• Not checked yetcites [27] Amato, 1997, Congestive heart failure predicts the development of non-insulin-dependent diabetes mellitus in the elderly. The Osservatorio Geriatrico Regione Campania Group, Diabetes Metab
• Not checked yetcites [59] Tenenbaum, 2003, Functional class in patients with heart failure is associated with the development of diabetes, Am J Med source

In the paper

“In a Danish nationwide cohort study, 8% of HF patients developed T2DM over 3 years, and the severity of HF was associated with a stepwise increased risk of developing T2DM.54”

What the sources say

• Not checked yetcites [54] Demant, 2014, Association of heart failure severity with risk of diabetes: a Danish nationwide cohort study, Diabetologia source

In the paper

“Notably, HF treatment with angiotensin-converting enzyme (ACE) inhibitors was shown to lower the incidence of T2DM in HFrEF patients;”

What the sources say

• Not checked yetcites [58] Vermes, 2003, Enalapril reduces the incidence of diabetes in patients with chronic heart failure: insight from the Studies Of Left Ventricular Dysfunction (SOLVD), Circulation source

In the paper

“In clinical trials of chronic HF patients, the prevalence of T2DM was around 30%, irrespective of HF phenotype (i.e.HFrEF and HFpEF) (Table 3).31 -48”

What the sources say

• Not checked yetcites [31] McMurray, 2014, PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure, N Engl J Med source
• Not checked yetcites [32] Swedberg, 2010, Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study, Lancet source
• Not checked yetcites [33] Ruschitzka, 2013, EchoCRT Study Group. Cardiac-resynchronization therapy in heart failure with a narrow QRS complex, N Engl J Med source
• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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 yetcites [93] Dauriz, 2017, Prognostic impact of diabetes on long-term survival outcomes in patients with heart failure: a meta-analysis, Diabetes Care source

In the paper

“In patients with HF, data from observational and clinical trials demonstrate an increased risk for new-onset T2DM compared to patients without HF.”

What the sources say

• Not checked yetcites [10] Nichols, 2001, Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors, Diabetes Care source
• Not checked yetcites [54] Demant, 2014, Association of heart failure severity with risk of diabetes: a Danish nationwide cohort study, Diabetologia source
• Not checked yetcites [55] Ingle, 2006, Diabetes lowers six-minute walk test performance in heart failure, J Am Coll Cardiol source
• Not checked yetcites [56] Preiss, 2009, Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity Investigators. Predictors of development of diabetes in patients with chronic heart failure in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program, Diabetes Care source

In the paper

“marked regional differences have been observed both in Europe and in rest of the world.”

What the sources say

• Not checked yetcites [9] Thrainsdottir, 2005, The association between glucose abnormalities and heart failure in the population-based Reykjavik study, Diabetes Care source
• Not checked yetcites [27] Amato, 1997, Congestive heart failure predicts the development of non-insulin-dependent diabetes mellitus in the elderly. The Osservatorio Geriatrico Regione Campania Group, Diabetes Metab
• Not checked yetcites [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

In the paper

“Conversely, HFrEF is an independent predictor of fatal and non-fatal clinical outcomes in patients with T2DM.2,3”

What the sources say

• Not checked yetcites [2] MacDonald, 2008, Diabetes, left ventricular systolic dysfunction, and chronic heart failure, Eur Heart J source
• Not checked yetcites [3] Vaur, 2003, DIABHYCAR Study Group. Development of congestive heart failure in type 2 diabetic patients with microalbuminuria or proteinuria: observations from the DIABHYCAR (type 2 DIABetes, Hypertension, CArdiovascular Events and Ramipril) study, Diabetes Care source

In the paper

“as demonstrated by the CHARM program, in which 7.8% of patients developed T2DM over 2.8 years.55,56”

What the sources say

• Not checked yetcites [55] Ingle, 2006, Diabetes lowers six-minute walk test performance in heart failure, J Am Coll Cardiol source
• Not checked yetcites [56] Preiss, 2009, Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity Investigators. Predictors of development of diabetes in patients with chronic heart failure in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program, Diabetes Care source

In the paper

“Patients with pre-diabetes in the ARIC study also had more HF than those without pre-diabetes.68”

What the sources say

• Not checked yetcites [68] Matsushita, 2010, The association of hemoglobin a1c with incident heart failure among people without diabetes: the Atherosclerosis Risk in Communities Study, Diabetes source

In the paper

“However, with longer-term follow-up, an association between T2DM and worse outcomes in HF patients becomes evident.”

What the sources say

• Not checked yetcites [45] Sarma, 2013, Association between diabetes mellitus and post-discharge outcomes in patients hospitalized with heart failure: findings from the EVEREST trial, Eur J Heart Fail source
• Not checked yetcites [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 yetcites [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 yetcites [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

In the paper

“and in the Netherlands a significantly higher risk of death (HR 3.19) 26 attributed to T2DM.”

What the sources say

• Not checked yetcites [26] Mosterd, 2001, The prognosis of heart failure in the general population: the Rotterdam Study, Eur Heart J source

In the paper

“T2DM is an independent risk factor for the development of HF. 10”

What the sources say

• Not checked yetcites [10] Nichols, 2001, Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors, Diabetes Care source

In the paper

“Likewise, all studies of the effect of T2DM on mortality in HF outpatients have found a higher mortality risk attributable to T2DM (Table 4).”

In the paper

“Patients with T2DM and both HFrEF 1,34,69,70 and HFpEF 1 have worse NYHA functional class and more HF-related symptoms and signs than patients without T2DM, despite having similar ejection fraction.69,70”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [70] Suskin, 2000, Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure, Eur Heart J source

In the paper

“Indeed, in the ARIC study, higher HbA 1c levels in T2DM patients were associated with significantly more incident HF cases than in patients with T2DM and lower HbA 1c levels.65”

What the sources say

• Not checked yetcites [65] Pazin-Filho, 2008, HbA 1c as a risk factor for heart failure in persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) study, Diabetologia source

In the paper

“Most trials also demonstrated worse quality of life in patients with T2DM and concurrent HF (both HFrEF and HFpEF), as compared to patients without T2DM.40,69”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“In Sweden, there was a moderately higher risk (HR 1.60) 53”

What the sources say

• Not checked yetcites [53] Johansson, 2015, Risk factors, treatment and prognosis in men and women with heart failure with and without diabetes, Heart source

In the paper

“Similarly, in observational studies (NHANES 64 and ARIC 65 ), the incidence of HF in patients with T2DM was higher than in those without T2DM, with the corresponding hazard ratios (HRs) of 1.85 and 3.54.”

What the sources say

• Not checked yetcites [64] He, 2001, Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study, Arch Intern Med source
• Not checked yetcites [65] Pazin-Filho, 2008, HbA 1c as a risk factor for heart failure in persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) study, Diabetologia source

In the paper

“In the OPTIMIZE-HF, ADHERE and Get With the Guidelines-HF registries in the United States, T2DM was not associated with higher in-hospital mortality.82 -85”

What the sources say

• Not checked yetcites [82] Greenberg, 2007, Influence of diabetes on characteristics and outcomes in patients hospitalized with heart failure: a report from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF), Am Heart J source
• Not checked yetcites [83] Kapoor, 2011, Diabetes, quality of care, and in-hospital outcomes in patients hospitalized with heart failure, Am Heart J source
• Not checked yetcites [84] O'Connor, 2008, Predictors of mortality after discharge in patients hospitalized with heart failure: an analysis from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF), Am Heart J source
• Not checked yetcites [85] Yancy, 2006, ADHERE Scientific Advisory Committee and Investigators. Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database, J Am Coll Cardiol source

In the paper

“Also, in patients from Scotland, T2DM increased mid-to-long-term mortality following hospitalization for HF. 87”

What the sources say

• Not checked yetcites [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

In the paper

“In elderly patients with T2DM, the incidence of HF was two-fold higher compared to patients without T2DM (121 vs. 62 cases/1000 patient-years).62”

What the sources say

• Not checked yetcites [62] Aronow, 1999, Incidence of heart failure in 2,737 older persons with and without diabetes mellitus, Chest source

In the paper

“Additionally, in the Rotterdam study, T2DM was associated with an excess risk for CV death (HR 3.25) that was similar to the risk of all-cause mortality.26”

What the sources say

• Not checked yetcites [26] Mosterd, 2001, The prognosis of heart failure in the general population: the Rotterdam Study, Eur Heart J source

In the paper

“Conversely, in the ALARM registry (six European countries, Mexico and Australia), and in the European Society of Cardiology (ESC) HF Long-Term Registry, T2DM was independently associated with a higher risk of in-hospital mortality.51,86”

What the sources say

• Not checked yetcites [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 yetcites [86] Parissis, 2012, Acute heart failure in patients with diabetes mellitus: clinical characteristics and predictors of in-hospital mortality, Int J Cardiol source

In the paper

“There is a suggestion from some cohorts 82,87 that short-term mortality in HF patients post-discharge may be similar or slightly lower in those with T2DM.”

What the sources say

• Not checked yetcites [82] Greenberg, 2007, Influence of diabetes on characteristics and outcomes in patients hospitalized with heart failure: a report from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF), Am Heart J source
• Not checked yetcites [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

In the paper

“Likewise, in the ESC HF Long-Term Registry, the presence of T2DM was independently associated with increased 1-year all-cause mortality.51,73”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“In a retrospective cohort followed for up to 72 months, patients with T2DM were more likely to develop HF than patients without T2DM (incidence rate 30.9 vs. 12.4/1000 person-years, rate ratio 2.5).61”

What the sources say

• Not checked yetcites [61] Nichols, 2004, The incidence of congestive heart failure in type 2 diabetes: an update, Diabetes Care source

In the paper

“In the UKPDS 35 trial including newly diagnosed diabetic patients, HF incidence steeply increased with the severity of dysglycaemia ranging from 2.3 to 11.9/1000 person-years for patients with glycated haemoglobin (HbA 1c ) <6% and HbA 1c >10%, respectively.63”

What the sources say

• Not checked yetcites [63] Stratton, 2000, Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study, BMJ source

In the paper

“For example, in the EVEREST trial in which patients were followed for 9.9 months after a HF hospitalization, T2DM conferred a slightly higher mortality.45”

What the sources say

• Not checked yetcites [45] Sarma, 2013, Association between diabetes mellitus and post-discharge outcomes in patients hospitalized with heart failure: findings from the EVEREST trial, Eur J Heart Fail source

In the paper

“A similar U-shaped curve was found in a single-centre study from Scotland.105”

What the sources say

• Not checked yetcites [105] Elder, 2016, Mean HbA1c and mortality in diabetic individuals with heart failure: a population cohort study, Eur J Heart Fail source

In the paper

“In a population-based Danish study, which followed patients for 6.8 years, patients with T2DM and HF had higher mortality whether or not they had CAD.96”

What the sources say

• Not checked yetcites [96] Andersson, 2010, Long-term impact of diabetes in patients hospitalized with ischemic and non-ischemic heart failure, Scand Cardiovasc J source

In the paper

“and the observed long-term risk appears greater in patients with chronic than in those with acute HF. 93”

What the sources say

• Not checked yetcites [93] Dauriz, 2017, Prognostic impact of diabetes on long-term survival outcomes in patients with heart failure: a meta-analysis, Diabetes Care source

In the paper

“The majority of the available data suggests that T2DM is associated with higher risk of mortality in both patients of ischaemic and non-ischaemic aetiology (Table 6).29,88,94,96 -99”

What the sources say

• Not checked yetcites [29] From, 2006, Diabetes in heart failure: prevalence and impact on outcome in the population, Am J Med source
• Not checked yetcites [88] Shindler, 1996, Diabetes mellitus, a predictor of morbidity and mortality in the Studies of Left Ventricular Dysfunction (SOLVD) Trials and Registry, Am J Cardiol source
• Not checked yetcites [94] Domanski, 2003, The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial, J Am Coll Cardiol source
• Not checked yetcites [96] Andersson, 2010, Long-term impact of diabetes in patients hospitalized with ischemic and non-ischemic heart failure, Scand Cardiovasc J source
• Not checked yetcites [97] De Groote, 2004, Impact of diabetes mellitus on long-term survival in patients with congestive heart failure, Eur Heart J source
• Not checked yetcites [98] Dries, 2001, Prognostic impact of diabetes mellitus in patients with heart failure according to the etiology of left ventricular systolic dysfunction, J Am Coll Cardiol source
• Not checked yetcites [99] Brophy, 2004, A multivariate model for predicting mortality in patients with heart failure and systolic dysfunction, Am J Med source

In the paper

“In the BEST trial, T2DM was an independent risk factor for death from pump failure.94”

What the sources say

• Not checked yetcites [94] Domanski, 2003, The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial, J Am Coll Cardiol source

In the paper

“In one single-centre observational study of 123 young patients with advanced HF and T2DM, patients with a HbA 1c of <7% had higher rates of all-cause mortality.106”

What the sources say

• Not checked yetcites [106] Eshaghian, 2006, An unexpected inverse relationship between HbA1c levels and mortality in patients with diabetes and advanced systolic heart failure, Am Heart J source

In the paper

“In the CHARM trial, patients with T2DM and both HFrEF and HFpEF were more likely to die of all subtypes of CV death [i.e.death due to HF, sudden cardiac death (SCD), death due to MI and death due to stroke]. 1”

What the sources say

• Not checked yetcites [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

In the paper

“The PARADIGM-HF study also reported that patients with T2DM and HFrEF were more likely to die of CV as well as all-cause mortality compared with patients without T2DM.69”

What the sources say

• Not checked yetcites [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

In the paper

“A 1% increase in HbA 1c was associated with an increased HR of 1.1 for CV mortality.104”

What the sources say

• Not checked yetcites [104] Gerstein, 2008, The hemoglobin A1c level as a progressive risk factor for cardiovascular death, hospitalization for heart failure, or death in patients with chronic heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program, Arch Intern Med source

In the paper

“In three early clinical trials (SOLVD, 98 BEST, 94 and DIG 102 )t h er i s k appeared to be confined to those with an ischaemic aetiology.”

What the sources say

• Not checked yetcites [98] Dries, 2001, Prognostic impact of diabetes mellitus in patients with heart failure according to the etiology of left ventricular systolic dysfunction, J Am Coll Cardiol source
• Not checked yetcites [94] Domanski, 2003, The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial, J Am Coll Cardiol source
• Not checked yetcites [102] Abdul-Rahim, 2016, Efficacy and safety of digoxin in patients with heart failure and reduced ejection fraction according to diabetes status: an analysis of the Digitalis Investigation Group (DIG) trial, Int J Cardiol source

In the paper

“In the CHARM trial, patients with both HFrEF and HFpEF had higher mortality attributed to T2DM whether or not they had CAD. 1”

What the sources say

• Not checked yetcites [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

In the paper

“In the CHARM trial, high HbA 1c was associated with increased all-cause and CV mortality in patients with T2DM and both HFrEF and HFpEF.104”

What the sources say

• Not checked yetcites [104] Gerstein, 2008, The hemoglobin A1c level as a progressive risk factor for cardiovascular death, hospitalization for heart failure, or death in patients with chronic heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program, Arch Intern Med source

In the paper

“In the DIAMOND trial, T2DM was associated with a higher risk of mortality in both ischaemic and non-ischaemic HF. 100”

What the sources say

• Not checked yetcites [100] Gustafsson, 2004, Danish Investigatord of Arrhythmia and Mortality on Dofetilde Study Group. Influence of diabetes and diabetes-gender interaction on the risk of death in patients hospitalized with congestive heart failure, J Am Coll Cardiol source

In the paper

“Additionally, in the same study, T2DM had a greater association with higher all-cause and CV mortality in patients with HFpEF than HFrEF. 1”

What the sources say

• Not checked yetcites [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

In the paper

“The greater relative benefit for the composite primary endpoint (all-cause mortality or HF hospitalization) of high-dose lisinopril was similar in patients with and without T2DM.”

What the sources say

• Not checked yetcites [143] Packer, 1999, Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group, Circulation source
• Not checked yetcites [144] Rydén, 2000, Efficacy and safety of high-dose lisinopril in chronic heart failure patients at high cardiovascular risk, including those with diabetes mellitus. Results from the ATLAS trial, Eur Heart J source

In the paper

“The MERIT-HF trial reported similar efficacy and safety of metoprolol succinate in patients with and ©2018 The Authors European Journal of Heart Failure ©2018 European Society of Cardiology without T2DM.37”

What the sources say

• Not checked yetcites [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

In the paper

“However, because patients with T2DM were at greater risk, the absolute benefit of high-dose lisinopril was larger in patients with T2DM.144”

What the sources say

• Not checked yetcites [144] Rydén, 2000, Efficacy and safety of high-dose lisinopril in chronic heart failure patients at high cardiovascular risk, including those with diabetes mellitus. Results from the ATLAS trial, Eur Heart J source

In the paper

“In the overall CHARM program, patients with T2DM had double the risk of developing hyperkalaemia on candesartan compared to those without T2DM.147”

What the sources say

• Not checked yetcites [147] Desai, 2007, Incidence and predictors of hyperkalemia in patients with heart failure: an analysis of the CHARM Program, J Am Coll Cardiol source

In the paper

“The treatment effect was again not different in the subgroup of patients with T2DM compared to those without T2DM (HR 0.96; interaction P=0.35).”

What the sources say

• Not checked yetcites [146] Konstam, 2009, Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial, Lancet source

In the paper

“A subsequent trial (HEAAL 146 ) showed that 150 mg daily of losartan was superior to 50 mg daily in reducing the risk of death or HF hospitalization”

What the sources say

• Not checked yetcites [146] Konstam, 2009, Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial, Lancet source

In the paper

“In clinical trials, all pharmacological and device therapies for HF were similarly effective whether or not patients had T2DM.”

In the paper

“The treatment effect on mortality was similar in patients with and without T2DM (HRs 0.56 and 0.59, respectively).”

What the sources say

• Not checked yetcites [163] Taylor, 2007, Early and sustained benefit on event-free survival and heart failure hospitalization from fixed-dose combination of isosorbide dinitrate/hydralazine: consistency across subgroups in the African-American Heart Failure Trial, Circulation source

In the paper

“For the endpoint of all-cause mortality, ACE-inhibitors had a similar treatment benefit in subjects with and without T2DM (HR 0.84 and 0.85, respectively).”

What the sources say

• Not checked yetcites [142] Shekelle, 2003, Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials, J Am Coll Cardiol source

In the paper

“A third meta-analysis that focused on seven trials using carvedilol, including a post-MI trial, revealed a similar, significant reduction in the risk for mortality with carvedilol in patients with and without T2DM (28% and 37%, respectively, interaction P=0.25).157”

What the sources say

• Not checked yetcites [157] Bell, 2006, The effect of carvedilol on mortality risk in heart failure patients with diabetes: results of a meta-analysis, Curr Med Res Opin source

In the paper

“There are no specific constraints to HF treatment in T2DM patients as recommended by the 2016 ESC guidelines for the management of HF. 116”

What the sources say

• Not checked yetcites [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

In the paper

“and a two-to four-fold higher CAD-and stroke-related mortality.139 -141”

What the sources say

• Not checked yetcites [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 yetcites [140] Kannel, 1979, Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham study, Diabetes Care source
• Not checked yetcites [141] Lee, 2000, Impact of diabetes on coronary artery disease in women and men: a meta-analysis of prospective studies, Diabetes Care source

In the paper

“These treatment benefits of beta-blockers in diabetic patients far outweigh the theoretical risks related to hypoglycaemia and minor changes in HbA 1c and serum lipids.”

In the paper

“In summary, beta-blockers in patients with T2DM and HF lead to significant improvements in morbidity and mortality that are consistent with results in patients without T2DM.”

In the paper

“AT 2 D M subgroup analysis has shown that the effect of sacubitril/valsartan compared with enalapril for the primary endpoint was similar in patients with and without T2DM (HR 0.83 and 0.77; respectively, interaction P=0.40).69”

What the sources say

• Not checked yetcites [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

In the paper

“Also, in the Val-HeFT, valsartan treatment led to a significant relative risk reduction in the co-primary composite endpoint (death or HF morbidity-mainly HF hospitalization) regardless of T2DM.145”

What the sources say

• Not checked yetcites [145] Maggioni, 2002, Val-HeFT Investigators (Valsartan Heart Failure Trial). Effects of valsartan on morbidity and mortality in patients with heart failure not receiving angiotensin-converting enzyme inhibitors, J Am Coll Cardiol source

In the paper

“The occurrence of adverse effects with high-dose lisinopril was similar in those with and without T2DM with respect to hypotension/dizziness (35% vs. 32%), renal dysfunction/hyperkalaemia (29% vs. 22%) and cough (12% vs. 10%).144”

What the sources say

• Not checked yetcites [144] Rydén, 2000, Efficacy and safety of high-dose lisinopril in chronic heart failure patients at high cardiovascular risk, including those with diabetes mellitus. Results from the ATLAS trial, Eur Heart J source

In the paper

“In the PARADIGM-HF trial, sacubitril/valsartan was superior to the ACE-inhibitor enalapril in reducing the risks of death and HF hospitalization (primary endpoint) in patients with HFrEF.31”

What the sources say

• Not checked yetcites [31] McMurray, 2014, PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure, N Engl J Med source

In the paper

“The mortality benefit of spironolactone in the RALES trial and eplerenone in the EMPHASIS-HF trial was consistent in T2DM and non-T2DM patients with HFrEF.158,159”

What the sources say

• Not checked yetcites [158] Pitt, 1999, The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators, N Engl J Med source
• Not checked yetcites [159] Zannad, 2011, EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms, N Engl J Med source

In the paper

“In the only RCT of insulin vs. placebo [ORIGIN, 12 537 people with CV risk factors plus impaired fasting glucose, impaired glucose tolerance, or T2DM (i.e.not in patients with HF)], insulin was not associated with higher rates of HF hospitalization than placebo.187”

What the sources say

• Not checked yetcites [187] Gerstein, 2012, Basal insulin and cardiovascular and other outcomes in dysglycemia, N Engl J Med source

In the paper

“In relation to T2DM status, both COMPANION (41%o fT 2 D M patients), and CARE-HF (29% of T2DM patients) demonstrated similar effectiveness of CRT for the reduction in mortality and HF hospitalization.171,172”

What the sources say

• Not checked yetcites [171] Ghali, 2007, Influence of diabetes on cardiac resynchronization therapy with or without defibrillator in patients with advanced heart failure, J Card Fail source
• Not checked yetcites [172] Hoppe, 2007, Effect of cardiac resynchronization on morbidity and mortality of diabetic patients with severe heart failure, Diabetes Care source

In the paper

“In the subanalysis of the STICH trial, there was no significant difference between patients with (40%) and without T2DM with respect to the primary outcome of all-cause mortality.177”

What the sources say

• Not checked yetcites [177] MacDonald, 2015, Clinical characteristics and outcomes of patients with and without diabetes in the Surgical Treatment for Ischemic Heart Failure (STICH) trial, Eur J Heart Fail source

In the paper

“Remarkably, despite the use of insulin and sulphonylureas for decades, there are no other placebo-controlled randomized trials.”

In the paper

“Previous concerns that metformin may cause metabolic acidosis are no longer justified.2”

What the sources say

• Not checked yetcites [2] MacDonald, 2008, Diabetes, left ventricular systolic dysfunction, and chronic heart failure, Eur Heart J source

In the paper

“Whether or not metformin is efficacious or safe is inconclusive.”

In the paper

“Patients at greatest risk were those with a history of HF, an estimated glomerular filtration rate (eGFR) ≤60 mL/min, or elevated baseline levels of N-terminal pro B-type natriuretic peptide (NT-proBNP).16”

What the sources say

• Not checked yetcites [16] Scirica, 2015, Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial, Circulation

In the paper

“Also, subgroup analysis of the RAFT trial showed that the benefit of CRT-D was similar in patients with and without T2DM.170”

What the sources say

• Not checked yetcites [170] Tang, 2010, Resynchronization-Defibrillation for Ambulatory Heart Failure Trial Investigators. Cardiac-resynchronization therapy for mild-to-moderate heart failure, N Engl J Med source

In the paper

“Coronary artery disease is the leading cause of premature mortality in patients with T2DM”

What the sources say

• Not checked yetcites [174] Howard, 2006, Coronary heart disease risk equivalence in diabetes depends on concomitant risk factors, Diabetes Care source
• Not checked yetcites [175] Juutilainen, 2005, Type 2 diabetes as a “coronary heart disease equivalent”: an 18-year prospective population-based study in Finnish subjects, Diabetes Care source

In the paper

“Likewise, sitagliptin in the TECOS trial had no signal of excess rates of HF. 18,185”

What the sources say

• Not checked yetcites [18] Green, 2015, TECOS Study Group. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes, N Engl J Med source
• Not checked yetcites [185] McGuire, 2016, Association between sitagliptin use and heart failure hospitalization and related outcomes in type 2 diabetes mellitus: secondary analysis of a randomized clinical trial, JAMA Cardiol source

In the paper

“In pre-specified subgroup analysis, there was no significant difference in treatment effect in patients with and without T2DM (HRs 0.92 and 0.85, respectively, interaction P=0.60).”

What the sources say

• Not checked yetcites [166] Kober, 2016, Defibrillator implantation in patients with nonischemic systolic heart failure, N Engl J Med source

In the paper

“In the RECORD 112 and the PROactive trials, 183 patients randomized to TZDs, rosiglitazone and pioglitazone, respectively, had more HF events than those on placebo.”

What the sources say

• Not checked yetcites [112] Komajda, 2010, Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial, Eur Heart J source
• Not checked yetcites [183] Lago, 2007, Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials, Lancet source

In the paper

“In observational studies in HF, insulin was associated with higher mortality rates than metformin.179”

What the sources say

• Not checked yetcites [179] MacDonald, 2010, Treatment of type 2 diabetes and outcomes in patients with heart failure: a nested case-control study from the U.K. General Practice Research Database, Diabetes Care source

In the paper

“There have been similar concerns with sulphonylureas which, as insulin secretagogues, have also been associated with higher death rates than metformin.2”

What the sources say

• Not checked yetcites [2] MacDonald, 2008, Diabetes, left ventricular systolic dysfunction, and chronic heart failure, Eur Heart J source

In the paper

“In MADIT-CRT, CRT-D treatment, compared with optimal medical therapy plus ICD, led to a similar reduction in the risk of all-cause death or HF hospitalization in patients with and without T2DM (adjusted HRs 0.56 and 0.67, respectively).169,173”

What the sources say

• Not checked yetcites [169] Moss, 2009, MADIT-CRT Trial Investigators. Cardiac-resynchronization therapy for the prevention of heart-failure events, N Engl J Med source
• Not checked yetcites [173] Martin, 2011, Cardiac resynchronization therapy reduces the risk of cardiac events in patients with diabetes enrolled in the multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy (MADIT-CRT), Circ Heart Fail source

In the paper

“In large observational studies, insulin is associated with higher mortality rates than metformin.2”

What the sources say

• Not checked yetcites [2] MacDonald, 2008, Diabetes, left ventricular systolic dysfunction, and chronic heart failure, Eur Heart J source

In the paper

“This was based on large observational studies where metformin was associated with lower mortality and HF hospitalization rates than other T2DM drugs (primarily insulin and sulphonylureas). 2”

What the sources say

• Not checked yetcites [2] MacDonald, 2008, Diabetes, left ventricular systolic dysfunction, and chronic heart failure, Eur Heart J source

In the paper

“In the SAVOR-TIMI 53 trial (saxagliptin vs. placebo), saxagliptin significantly increased the risk for HF hospitalizations (HR 1.27, P=0.007).16”

What the sources say

• Not checked yetcites [16] Scirica, 2015, Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial, Circulation

In the paper

“In an adjusted analysis, exercise training led to an 11% (P=0.03)reduction in the primary composite outcome of all-cause mortality or all-cause hospitalization.”

What the sources say

• Not checked yetcites [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

In the paper

“In the EXAMINE trial of alogliptin vs. placebo in patients who had had an acute coronary syndrome, there was not a statistically significant increase in the risk of HF hospitalizations in patients randomized to alogliptin.19,184”

What the sources say

• Not checked yetcites [19] White, 2013, Alogliptin after acute coronary syndrome in patients with type 2 diabetes, N Engl J Med source
• Not checked yetcites [184] Zannad, 2015, Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial, Lancet source

In the paper

“Some observational data suggest an increased mortality risk with sulphonylureas compared with metformin.179,182”

What the sources say

• Not checked yetcites [179] MacDonald, 2010, Treatment of type 2 diabetes and outcomes in patients with heart failure: a nested case-control study from the U.K. General Practice Research Database, Diabetes Care source
• Not checked yetcites [182] Tzoulaki, 2009, Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database, BMJ source

In the paper

“In observational studies in HF, metformin is associated with lower mortality rates than sulphonylureas or insulin.179”

What the sources say

• Not checked yetcites [179] MacDonald, 2010, Treatment of type 2 diabetes and outcomes in patients with heart failure: a nested case-control study from the U.K. General Practice Research Database, Diabetes Care source

In the paper

“T2DM was an independent risk factor for reduced 10-year survival in a large registry of 22 385 transplant patients.178”

What the sources say

• Not checked yetcites [178] Kilic, 2012, What predicts long-term survival after heart transplantation? An analysis of 9,400 ten-year survivors, Ann Thorac Surg source

In the paper

“In these trials, GLP-1 receptor agonists had a neutral effect on the risk for HF hospitalization.”

What the sources say

• Not checked yetcites [22] Marso, 2016, LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes, N Engl J Med source
• Not checked yetcites [23] Pfeffer, 2015, Lixisenatide in patients with type 2 diabetes and acute coronary syndrome, N Engl J Med source
• Not checked yetcites [24] Holman, 2017, EXSCEL Study Group. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes, N Engl J Med source
• Not checked yetcites [186] Marso, 2016, Semaglutide and cardiovascular outcomes in patients with type 2 diabetes, N Engl J Med source

In the paper

“Not all DPP4 inhibitors are associated with higher rates of HF (Table 8).16 -24,184-186”

What the sources say

• Not checked yetcites [16] Scirica, 2015, Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial, Circulation
• Not checked yetcites [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 yetcites [18] Green, 2015, TECOS Study Group. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes, N Engl J Med source
• Not checked yetcites [19] White, 2013, Alogliptin after acute coronary syndrome in patients with type 2 diabetes, N Engl J Med source
• Not checked yetcites [20] Zinman, 2015, Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes, N Engl J Med source
• Not checked yetcites [21] Neal, 2017, CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes, N Engl J Med source
• Not checked yetcites [22] Marso, 2016, LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes, N Engl J Med source
• Not checked yetcites [23] Pfeffer, 2015, Lixisenatide in patients with type 2 diabetes and acute coronary syndrome, N Engl J Med source
• Not checked yetcites [24] Holman, 2017, EXSCEL Study Group. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes, N Engl J Med source
• Not checked yetcites [184] Zannad, 2015, Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial, Lancet source

In the paper

“Patients with T2DM did not experience a higher rate of complications related to device implantation, including infection.170”

What the sources say

• Not checked yetcites [170] Tang, 2010, Resynchronization-Defibrillation for Ambulatory Heart Failure Trial Investigators. Cardiac-resynchronization therapy for mild-to-moderate heart failure, N Engl J Med source

In the paper

“There are no RCTs of metformin in patients with T2DM and HF.”

In the paper

“In a placebo-controlled FIGHT trial, of patients with HFrEF, with and without T2DM (41%), liraglutide was not associated with an improvement in the composite primary endpoint of death, rehospitalization and NT-proBNP change.181”

What the sources say

• Not checked yetcites [181] Margulies, 2016, Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial, JAMA source

In the paper

“In patients with T2DM without HF, some drugs have been shown to increase the risk of HF hospitalizations (i.e.rosiglitazone, pioglitazone and saxagliptin)”

In the paper

“Two large RCTs that assessed CV safety of the sodium-glucose co-transporter type 2 (SGLT2) inhibitors, empagliflozin and canagliflozin, have shown a significant reduction in HF hospitalization with both drugs.20,189”

What the sources say

• Not checked yetcites [20] Zinman, 2015, Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes, N Engl J Med source
• Not checked yetcites [189] Mahaffey, 2018, Canagliflozin for primary and secondary prevention of cardiovascular events: results from the CANVAS Program (Canagliflozin Cardiovascular Assessment Study), Circulation source

In the paper

“Large clinical trials investigating CV safety of newer antidiabetic drugs in patients with CV disease or at high CV risk have demonstrated that GLP-1 receptor agonists and a DPP4 inhibitor, sitagliptin, have a neutral effect on the risk of HF hospitalisations.”

In the paper

“A small randomized, placebo-controlled trial of albiglutide in HFrEF showed no effect on left ventricular function and 6-minute walk distance.190”

What the sources say

• Not checked yetcites [190] Lepore, 2016, Effects of the novel long-acting GLP-1 agonist, albiglutide, on cardiac function, cardiac metabolism, and exercise capacity in patients with chronic heart failure and reduced ejection fraction, JACC Heart Fail source

In the paper

“There has been uncertainty about the safety of older T2DM drugs such as insulin and sulphonlyureas in patients with T2DM and HF but there are no RCTs to allow firm conclusions.”

In the paper

“I nt h eL I V Et r i a l ,i np a t i e n t sw i t hs t a b l eH F r E F ,w i t ha n dw i t hout T2DM, there were no significant changes in left ventricular ejection fraction between patients randomized on liraglutide or placebo.180”

What the sources say

• Not checked yetcites [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

In the paper

“In the EMPA-REG OUTCOME trial (n=7020), including patients with T2DM, established CV disease and eGFR >30 mL/min/1.73m 2 , there was a major reduction in HF hospitalization (HR 0.65) with empagliflozin compared with placebo.20”

What the sources say

• Not checked yetcites [20] Zinman, 2015, Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes, N Engl J Med source

In the paper

“In addition, SGLT2 inhibitors, empagliflozin and canagliflozin demonstrated a significant reduction in the risk of HF hospitalizations in patients with T2DM.”

In the paper

“Similarly, no signal for a higher risk for HF hospitalization was seen with acarbose (vs.placebo) in patients with insulin resistance and CAD.188”

What the sources say

• Not checked yetcites [188] Holman, 2017, Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial, Lancet Diabetes Endocrinol source

In the paper

“A significant breakthrough in contemporary cardiology was the finding that some T2DM drugs are associated with a lower risk of HF hospitalization in patients with CV disease or at high risk of CV disease (Table 8).”

What the sources say

• Not checked yetcites [20] Zinman, 2015, Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes, N Engl J Med source
• Not checked yetcites [189] Mahaffey, 2018, Canagliflozin for primary and secondary prevention of cardiovascular events: results from the CANVAS Program (Canagliflozin Cardiovascular Assessment Study), Circulation source