New Antihyperglycemic Drugs and Heart Failure: Synopsis of Basic and Clinical Data.

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Term Occurence Count Dictionary
Insulin 1 endocrinologydiseasesdrugs
Liraglutide 1 endocrinologydiseasesdrugs
dapagliflozin 2 endocrinologydiseasesdrugs
rosiglitazone 2 endocrinologydiseasesdrugs
diabetes mellitus 6 endocrinologydiseases
hyperglycemia 1 endocrinologydiseases
metformin 3 endocrinologydiseasesdrugs
pioglitazone 2 endocrinologydiseasesdrugs
sitagliptin 7 endocrinologydiseasesdrugs

Graph of close proximity drug and disease terms (within 200 characters).

Note: If this graph is empty, then there are no terms that meet the proximity constraint.

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Select Drug Character Offset Drug Term Instance
Insulin 7937 on mechanical performance and this effect seems to be of particular importance in human myocardium. Insulin administration itself exerts positive inotropic effects in human ventricular myocardium via Ca2+-dependent
Liraglutide 16589 and a HbA1c ≥ 7%. Of the total enrolled subjects, 81.3% had preexisting cardiovascular diseases. Liraglutide significantly reduced the rate of the first occurrence of the primary endpoint (cardiovascular death,
dapagliflozin 23887 various class members.Activation of AMPK, for example, has only been shown for canagliflozin but not for dapagliflozin or empagliflozin [[86]]. However, a pathway most likely influenced by all SGLT-2 inhibitors in cardiomyocytes
dapagliflozin 25499 treatment, indicating towards a direct myocardial effect.This idea is also supported by the finding that dapagliflozin but not pioglitazone significantly improves cardiac function in a mouse model despite comparable glucose
metformin 25973 patients with an ideal body weight greater than 120% were randomly assigned to an intensive treatment with metformin or conventional treatment. A 39% relative risk reduction in fatal and nonfatal myocardial infarction
metformin 26398 performed with randomized clinical trials data [[90]] suggesting a cardiovascular benefit associated with metformin . A larger trial investigating the effect of metformin in nondiabetic hyperglycemia is currently ongoing
metformin 26452 suggesting a cardiovascular benefit associated with metformin. A larger trial investigating the effect of metformin in nondiabetic hyperglycemia is currently ongoing (ISRCTN 34875079).7. ConclusionWith new and emerging
pioglitazone 25521 towards a direct myocardial effect.This idea is also supported by the finding that dapagliflozin but not pioglitazone significantly improves cardiac function in a mouse model despite comparable glucose lowering effects.
pioglitazone 25708 comparable glucose lowering effects. Ejection fraction and isovolumetric relaxation time were not altered in pioglitazone , but E/A ratio and ventricular hypertrophy were both slightly improved.6. MetforminIn the United Kingdom
rosiglitazone 1034 raised alarm describing a significant increase in myocardial infarction with the thiazolidinedione rosiglitazone . The first results from completed cardiovascular outcome trials are already available: TECOS, SAVOR-TIMI,
rosiglitazone 2768 meta-analysis describing a relative 43% increase in myocardial infarction with the use of thiazolidinedione rosiglitazone [[1]]. The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) responded by mandating
sitagliptin 9255 substances, the amount and quality of available experimental data are heterogeneous.3. DPP-4 InhibitorsWhile sitagliptin , alogliptin, and saxagliptin were shown to be safe for the cardiovascular system in terms of the MACE,
sitagliptin 9867 significant. In contrast, TECOS did not show an increased rate for heart failure hospitalizations after sitagliptin administration, suggesting a potential difference between members of the DPP-4 inhibitor class. The
sitagliptin 12913 arrhythmias although the exact mechanism has not yet been determined [[38]].Similar effects are reported for sitagliptin in diabetic rats. Sitagliptin improved endothelial function [[39]] and attenuated cardiac remodeling
sitagliptin 13162 after myocardial infarction [[40]] while, in normoglycemic rats with induced myocardial infarction, sitagliptin prevented fatal arrhythmias by attenuating GIP-dependent resistin signaling [[41]] and in a PKA-dependent
sitagliptin 13306 attenuating GIP-dependent resistin signaling [[41]] and in a PKA-dependent pathway [[42]]. Moreover, sitagliptin attenuated changes in the electrophysiological function in hypertensive rats [[43]] and counteracted
sitagliptin 13757 reduction of parameters of diastolic dysfunction and myocardial stiffness via the cGMP-PKG pathway after sitagliptin administration in obese diabetic mice [[46]].Alogliptin could restore cardiac remodeling and prevent
sitagliptin 15323 ischemia [[53]]. Focusing on the cardiovascular system, vildagliptin seems to exert similar effects as sitagliptin [[54]]. However, no large cardiovascular outcome trial for vildagliptin is being performed.Finally,
Select Disease Character Offset Disease Term Instance
diabetes mellitus 8799 bidirectionally. Besides an HbA1c dependent increased risk of developing heart failure in patients with diabetes mellitus , the prevalence of diabetes in heart failure patients is known to increase markedly over time (3.8%
diabetes mellitus 11867 of NO and the reduction of cyclooxygenase-1-action derived vasoconstriction caused by induced type-2 diabetes mellitus in mice [[33]] and, similarly, leads to a restoration of damaged mitochondrial vascular function in
diabetes mellitus 16070 designed to assess the effects of lixisenatide on the cardiovascular outcome in patients with type-2 diabetes mellitus who had an acute coronary event within 180 days of screening. For the primary composite endpoint (cardiovascular
diabetes mellitus 16472 [[58]]. The LEADER trial assessed the cardiovascular safety of liraglutide in patients with type-2 diabetes mellitus and a HbA1c ≥ 7%. Of the total enrolled subjects, 81.3% had preexisting cardiovascular diseases. Liraglutide
diabetes mellitus 17020 group compared to the placebo group [[59]]. In the SUSTAIN-6 trial (semaglutide) patients with type-2 diabetes mellitus and established cardiovascular diseases, chronic heart failure, or chronic kidney disease, or ≥60
diabetes mellitus 17640 continue to hold promise that GLP-1 receptor agonists might improve CV morbidity in patients with type-2 diabetes mellitus . However, we do not yet fully understand the reasons for the diverging results in the currently published
hyperglycemia 26477 benefit associated with metformin. A larger trial investigating the effect of metformin in nondiabetic hyperglycemia is currently ongoing (ISRCTN 34875079).7. ConclusionWith new and emerging primarily antihyperglycemic

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