Effect of dipeptidyl peptidase-4 inhibitors on heart failure: A meta-analysis of randomized clinical trials

Kongwatcharapong, Junporn; Dilokthornsakul, P.; Nathisuwan, Surakit; Phrommintikul, Arintaya; Chaiyakunapruk, Nathorn

doi:10.1016/j.ijcard.2016.02.146

Cited by 65 publications

(41 citation statements)

References 72 publications

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“…Use of saxagliptin significantly increased the risk of HF by 21% especially among patients with high CV risk (RR 1.215; 95% CI: 1.028 to 1.437; P=0.022), while others were not associated with an increased HF risk (31). Age ≥65 years, diabetes duration of ≥10 years and BMI ≥30 kg/m 2 were associated with an increased risk of HF among patients using saxagliptin (31). Based on available data, the risk of HF with DPP-4 inhibitors is of definitive concern and appears to be drug-specific.…”

Section: Dpp-4 Inhibitorsmentioning

confidence: 96%

“…In a meta-analysis of 54 randomized controlled trials of DPP-4 inhibitors in 74,737 participants with a minimum follow-up of 12 weeks, DPP-4 inhibitors were not associated with an increased risk of HF compared to comparators (RR 1.106; 95% CI: 0.995 to 1.228; P=0.062) (31). The authors noted a differential effect of each DPP-4 inhibitor on the risk of HF.…”

Section: Dpp-4 Inhibitorsmentioning

confidence: 97%

“…More patients in the saxagliptin group than in the placebo group were hospitalized for HF (3.5% vs. 2.8%; HR, 1.27; 95% CI: 1.07 to 1.51; P=0.007) (30). A metaanalysis of randomized trials of DPP-4 inhibitors showed that saxagliptin was significantly associated with a 21% increased risk of HF (RR, 1.215; 95% CI: 1.028 to 1.437; P=0.022) (31). The EXAmination of CV outcoMes with alogliptIN versus standard of carE (EXAMINE) trial randomized 5,380 T2DM patients with either an acute MI or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and CV drug therapy for a median follow up of 40 months (32).…”

Section: Dpp-4 Inhibitorsmentioning

confidence: 99%

See 2 more Smart Citations

Cardiovascular benefits of the newer medications for treating type 2 diabetes mellitus

Yandrapalli¹,

Aronow²

2017

J. Thorac. Dis.

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Section: Dpp-4 Inhibitorsmentioning

confidence: 96%

Section: Dpp-4 Inhibitorsmentioning

confidence: 97%

Section: Dpp-4 Inhibitorsmentioning

confidence: 99%

See 1 more Smart Citation

Cardiovascular benefits of the newer medications for treating type 2 diabetes mellitus

Yandrapalli¹,

Aronow²

2017

J. Thorac. Dis.

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“…Indeed, these meta-analyses of RCTs with GLP-1RAs may be compared with those of RCTs with DPP-4 inhibitors [9,10], which showed that DPP-4 inhibitors were not associated with any increased risk of HF-related hospitalizations [10] except for saxagliptin [9], mainly because of the results of the SAVOR -TIMI 53 trial [7].…”

Section: Effects Of Liraglutide On Cardiac Function and Cardiovasculamentioning

confidence: 99%

“…HF is of major interest as it is the one cardiovascular outcome for which the risk has unequivocally been shown to be increased by some glucose-lowering therapies, particularly thiazolidinediones (glitazones) [4,5], whereas metformin appears to be safe [6]. Recently, some concerns have also been raised with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin, following the publication of the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR) -Thrombolysis in Myocardial Infarction (TIMI) 53 trial [7], a finding that casts some suspicion on the entire incretin-based pharmacological class [8][9][10]. In contrast, a marked, significant reduction in hospitalizations for HF has been reported with the sodium -glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) [11,12].…”

Section: Introductionmentioning

confidence: 99%

GLP-1 receptor agonists and heart failure in diabetes

Scheen

2017

Diabetes & Metabolism

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The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization. Such an increased risk has been consistently reported with thiazolidinediones (glitazones) and perhaps also with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR -TIMI 53), whereas a markedly decreased risk was highlighted with the sodium -glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME. Yet, the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on myocardial function remain controversial. Whereas some promising observations have been reported in various animal models, the effects of GLP-1RAs on myocardial function in humans are more heterogeneous, while the positive effect on left ventricular ejection fraction (LVEF), if any, appears to be inconsistent and rather modest in most patients with HF. However, no increased risk of hospitalization for HF has been reported with GLP-1RAs in meta-analyses of phase-II/III trials (exenatide, albiglutide, dulaglutide, liraglutide), demonstrating the safety of this pharmacological class, and such findings have been confirmed by three large prospective cardiovascular outcome trials (ELIXA with lixisenatide, LEADER with liraglutide and SUSTAIN-6 with semaglutide). In particular, LEADER reported a trend towards a reduction in HF hospitalization (-13%, P = 0.14), together with a significant reduction in cardiovascular and all-cause mortality in patients with T2D at risk of cardiovascular disease. These results are reassuring in the face of the somewhat negative results of the FIGHT trial, which evaluated the effects of liraglutide in patients with advanced HF and low LVEF, such that further studies and caution are now required when using this agent to treat such patients in clinical practice.

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European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose‐lowering drugs in patients with heart failure

Seferović

Coats

Ponikowski

et al. 2019

European J of Heart Fail

149

122

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Type 2 diabetes mellitus (T2DM) is common in patients with heart failure (HF) and associated with considerable morbidity and mortality. Significant advances have recently occurred in the treatment of T2DM, with evidence of several new glucose‐lowering medications showing either neutral or beneficial cardiovascular effects. However, some of these agents have safety characteristics with strong practical implications in HF [i.e. dipeptidyl peptidase‐4 (DPP‐4) inhibitors, glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA), and sodium–glucose co‐transporter type 2 (SGLT‐2) inhibitors]. Regarding safety of DPP‐4 inhibitors, saxagliptin is not recommended in HF because of a greater risk of HF hospitalisation. There is no compelling evidence of excess HF risk with the other DPP‐4 inhibitors. GLP‐1 RAs have an overall neutral effect on HF outcomes. However, a signal of harm suggested in two small trials of liraglutide in patients with reduced ejection fraction indicates that their role remains to be defined in established HF. SGLT‐2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) have shown a consistent reduction in the risk of HF hospitalisation regardless of baseline cardiovascular risk or history of HF. Accordingly, SGLT‐2 inhibitors could be recommended to prevent HF hospitalisation in patients with T2DM and established cardiovascular disease or with multiple risk factors. The recently completed trial with dapagliflozin has shown a significant reduction in cardiovascular mortality and HF events in patients with HF and reduced ejection fraction, with or without T2DM. Several ongoing trials will assess whether the results observed with dapagliflozin could be extended to other SGLT‐2 inhibitors in the treatment of HF, with either preserved or reduced ejection fraction, regardless of the presence of T2DM. This position paper aims to summarise relevant clinical trial evidence concerning the role and safety of new glucose‐lowering therapies in patients with HF.

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Effect of dipeptidyl peptidase-4 inhibitors on heart failure: A meta-analysis of randomized clinical trials

Cited by 65 publications

References 72 publications

Cardiovascular benefits of the newer medications for treating type 2 diabetes mellitus

Cardiovascular benefits of the newer medications for treating type 2 diabetes mellitus

GLP-1 receptor agonists and heart failure in diabetes

European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose‐lowering drugs in patients with heart failure

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