The heart failure burden of type 2 diabetes mellitus-a review of pathophysiology and interventions.

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Term Occurence Count Dictionary
rosiglitazone 3 endocrinologydiseasesdrugs
Glimepiride 1 endocrinologydiseasesdrugs
lactic acidosis 1 endocrinologydiseases
obesity 4 endocrinologydiseases
enalapril 3 endocrinologydiseasesdrugs
pioglitazone 4 endocrinologydiseasesdrugs
spironolactone 1 endocrinologydiseasesdrugs
metformin 3 endocrinologydiseasesdrugs
sitagliptin 2 endocrinologydiseasesdrugs
type 2 diabetes mellitus 3 endocrinologydiseases
Insulin 1 endocrinologydiseasesdrugs
dapagliflozin 2 endocrinologydiseasesdrugs
hypoglycemia 1 endocrinologydiseases
Liraglutide 6 endocrinologydiseasesdrugs
diabetes mellitus 6 endocrinologydiseases
hyperglycemia 3 endocrinologydiseases

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Select Drug Character Offset Drug Term Instance
Glimepiride 41881 Accidents Intervention Trial (TOSCA-IT) [[116]]), CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA®) trial [[117], [118]] and The Glycemia Reduction Approaches in Diabetes:
Insulin 42095 Diabetes: A Comparative Effectiveness Study (GRADE) [[119]] might provide further insights in these matters. Insulin With the expanding armamentarium of non-insulin therapies for T2DM, insulin initiation typically occurs
Liraglutide 9335 macroVascular Events, ELIXA: the Evaluation of LIXisenatide in Acute Coronary Syndrome trial, LEADER: the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results—a long term evaluation
Liraglutide 39212 With Sitagliptin, ELIXA: the Evaluation of LIXisenatide in Acute Coronary Syndrome trial, LEADER: the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results—a long term evaluation
Liraglutide 40085 With Sitagliptin, ELIXA: the Evaluation of LIXisenatide in Acute Coronary Syndrome trial, LEADER: the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results—a long term evaluation
Liraglutide 49035 thus far reported; the Evaluation of LIXisenatide in Acute Coronary Syndrome (ELIXA) trial and the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results—a long term evaluation
Liraglutide 50722 studies have suggested potentially adverse effects on cardiac function of liraglutide: the Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized
Liraglutide 51500 safety events (17 vs 11% in liraglutide and placebo). These findings were in line with the Effect of Liraglutide on Left Ventricular Function in Chronic Heart Failure Patients With and Without Type 2 Diabetes Mellitus
dapagliflozin 56259 https://clinicaltrials.gov/ct2/show/NCT01986881?term=vertis&rank=1.].In a meta-analysis of phase 2 and 3 trials with dapagliflozin there was no sign of increased risk of HF hospitalization as compared to placebo or comparator (HR 0.36
dapagliflozin 57739 [https://clinicaltrials.gov/ct2/show/NCT03057951?term=EMPEROR&rank=2., https://clinicaltrials.gov/ct2/show/NCT03057977?term=EMPEROR&rank=1.], or studies of dapagliflozin [https://www.astrazeneca.com/media-centre/press-releases/2016/astrazeneca-announces-two-new-phase-IIIb-trials-for-Forxiga-in-chronic-kidney-disease-and-chronic-heart-failure-120920161.html.],
enalapril 18210 27 monthsDrug studiedDigoxin vs placeboValsartan vs placeboCandesartan vs placeboIvabradine vs placeboLCZ696 vs enalapril Inclusion criteria/ EF criterion for entryHF with EF ≤ 45% and sinus rhythmHF NYHA class II-IV
enalapril 28013 by the number and type of non-cardiac comorbidities (including T2DM) regarding treatment effects of enalapril on outcomes [[86]] (Table 1 and Fig. 3a, b). Enalapril furthermore slowed LV remodeling and the development
enalapril 32399 reported a reduced risk for CV death and hospitalization for HF for ARNI when compared to treatment with enalapril in symptomatic patients with HFrEF (Table 2) [[27]]. The results were consistent across subgroups, including
metformin 40774 HF [[107]–[109]]. A later, larger systematic review supported this conclusion [[110]]. No RCTs of metformin indicate, however, a role in the prevention of HF or HF outcomes.SulphonylureasIn patients with newly
metformin 41216 second generation sulphonylureas might be associated with 18–30% increased risk of HF as compared to metformin [[113], [114]]. One Canadian retrospective study, based on the Saskatchewan Health records, reported
metformin 41424 reported similar results (i.e., increased HF admission rates associated with sulphonylurea as compared to metformin ), but when background characteristics (e.g., history of coronary heart disease, use of CV medication)
pioglitazone 1750 reporting benefits (empagliflozin and canagliflozin) and two reporting increased risk (saxagliptin, pioglitazone ). In vulnerable T2DM patients with concomitant HF, guideline-recommended HF drugs are effective. When
pioglitazone 7010 MRA, ARNI), and, as illustrated in Fig. 1b, in major CV outcome trials testing glucose-lowering drugs ( pioglitazone , GLP-1 receptor analogues, DPP-4 inhibitors, SGLT-2- inhibitors). In fact, the incremental risk for
pioglitazone 8823 HF hospitalization by prevalent HF in placebo arms of CV outcomes trials of glucose-lowering drugs ( pioglitazone [[29], [30]], lixisenatide [[31], [32]], liraglutide [[33], [34]], alogliptin [[35], [36]], saxagliptin
pioglitazone 43672 are insulin sensitizing drugs known to cause fluid retention. The class includes rosiglitazone and pioglitazone , which both in dedicated outcome trials were associated with increased risk of HF hospitalizations,
rosiglitazone 43654 arms.ThiazolidinedionesThiazolidinediones (TZDs) are insulin sensitizing drugs known to cause fluid retention. The class includes rosiglitazone and pioglitazone, which both in dedicated outcome trials were associated with increased risk of HF hospitalizations,
rosiglitazone 44435 similar extent [[130]]. One study aiming to understand the cardiac dynamics with TZD therapy found that rosiglitazone significantly increased left ventricular end-diastolic volume [[131]]. The use of TZDs is contraindicated
rosiglitazone 47800 end-systolic volumes was seen with vildagliptin [[132]], an effect of similar magnitude as observed with rosiglitazone therapy [[131]]. Finally, although no dedicated outcome study has been reported yet for linagliptin,
sitagliptin 8954 lixisenatide [[31], [32]], liraglutide [[33], [34]], alogliptin [[35], [36]], saxagliptin [[37], [38]], sitagliptin [[39], [40]], and empagliflozin [[41], [42]]) and the relative incidence rate ratio for HF hospitalization
sitagliptin 47033 4b). The Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS) investigated the effect of sitagliptin vs placebo in T2DM patients with established CVD, with neutral effect on the primary outcome (CV death,
spironolactone 26188 Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial explored the effect of spironolactone on a primary outcome of CV death, aborted cardiac arrest and hospitalization for HF in a population
Select Disease Character Offset Disease Term Instance
diabetes mellitus 63 Title: Heart Failure ReviewsThe heart failure burden of type 2 diabetes mellitus —a review of pathophysiology and interventionsAnne Pernille OfstadDan AtarLars GullestadGisle LangsletOdd
diabetes mellitus 599 significant “deadly duo.” The evidence for pharmacological treatment of HF in patients with type 2 diabetes mellitus (T2DM) stems typically from either subgroup analyses of patients that were recruited to randomized controlled
diabetes mellitus 2382 population. Its prevalence increases with age and comorbidities such as hypertension, obesity, and type 2 diabetes mellitus (T2DM) [[3]], and this has implications given the diabetes and obesity (i.e., “diabesity”) epidemic
diabetes mellitus 6152 discussionEpidemiology and prognosis of HF in T2DMThe Framingham study reported already in 1974 that men and women with diabetes mellitus (DM) had a 2-fold and 5-fold increased risk, respectively, of incident HF during 18 years of follow-up,
diabetes mellitus 17366 .0026NRNRNRReferences[[13], [17]][[20], [21]][[71], [72]][[73], [74]][[25], [26]]HF heart failure, EF ejection fraction, DM diabetes mellitus , RR relative risk, HR hazard ratio, CV cardiovascular, HR hazard ratio,*Morbidity defined as defined
diabetes mellitus 20901 (0.67, 0.94)References[[18], [19]][[75]][[22]][[24]][[27]]HF heart failure, EF ejection fraction, DM diabetes mellitus , RR relative risk, HR hazard ratio, CV cardiovascular, HR hazard ratio,*Morbidity defined as defined
hyperglycemia 10254 structural and functional changes (“diabetic cardiomyopathy”) [[43], [44]]. The hallmark of T2DM, namely hyperglycemia , is a major contributor, and observational data suggest an 8–16% increased risk of HF for each 1%-point
hyperglycemia 11634 remains to be fully elucidated [[44], [59], [60]] considering multiple interrelated factors including hyperglycemia and elevated levels of free fatty acids as observed in T2DM. These induce a shift in substrate metabolism
hyperglycemia 57155 intervention with a global risk factor approach (i.e., addressing hypertension, albuminuria, dyslipidemia, hyperglycemia , physical inactivity), which in a RCT proved to prevent deterioration in cardiac function in T2DM over
hypoglycemia 30276 potentially, underutilized in T2DM, perhaps due to fear of side effects, in particular blunting of symptoms of hypoglycemia . Post hoc analyses of the large β-blocker trials have furthermore reported some regional differences
lactic acidosis 40439 in T2DM patients with HF [[3]]. A previous contraindication for its use in HF, due to concerns for lactic acidosis , was removed by the FDA in 2007 [[106]] following retrospective studies reporting improved outcomes
obesity 2362 of the adult population. Its prevalence increases with age and comorbidities such as hypertension, obesity , and type 2 diabetes mellitus (T2DM) [[3]], and this has implications given the diabetes and obesity
obesity 2463 obesity, and type 2 diabetes mellitus (T2DM) [[3]], and this has implications given the diabetes and obesity (i.e., “diabesity”) epidemic we currently are facing [[4]]. Although improved evidence-based treatment
obesity 10443 increased risk of HF for each 1%-point increase in HbA1c [[45], [46]]. Furthermore, T2DM is associated with obesity and visceral adiposity (e.g., epicardial adipose tissue) which is associated with impaired myocardial
obesity 13932 stage, which may take several years, include comorbidities often seen in T2DM such as CAD, hypertension, obesity , and microvascular changes [[67]].HFrEF vs HFpEF in T2DMHF is categorized according to LVEF ≤ 40%
type 2 diabetes mellitus 56 Title: Heart Failure ReviewsThe heart failure burden of type 2 diabetes mellitus —a review of pathophysiology and interventionsAnne Pernille OfstadDan AtarLars GullestadGisle LangsletOdd
type 2 diabetes mellitus 592 it a significant “deadly duo.” The evidence for pharmacological treatment of HF in patients with type 2 diabetes mellitus (T2DM) stems typically from either subgroup analyses of patients that were recruited to randomized controlled
type 2 diabetes mellitus 2375 population. Its prevalence increases with age and comorbidities such as hypertension, obesity, and type 2 diabetes mellitus (T2DM) [[3]], and this has implications given the diabetes and obesity (i.e., “diabesity”) epidemic

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