Risk of hospitalization for heart failure in patients with type 2 diabetes newly treated with DPP-4 inhibitors or other oral glucose-lowering medications: a retrospective registry study on 127,555 patients from the Nationwide OsMed Health-DB Database

Fadini, Gian Paolo; Avogaro, Angelo; Esposti, Luca Degli; Russo, Pierluigi; Saragoni, Stefania; Buda, Stefano; Rosano, Giuseppe M.C.; Pecorelli, Sërgio; Pani, Luca

doi:10.1093/eurheartj/ehv301

Cited by 97 publications

(77 citation statements)

References 29 publications

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“…With DPP4i some studies showed an increased risk of MI and ischemic stroke [23,[27][28][29] or HF [22]. Contradictingly, other studies have shown a significantly lower HF risk [30] or a neutral effect on CV events [28].…”

Section: Discussionmentioning

confidence: 99%

Theeffect of Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Disease Risk in Type 2 Diabetes Mellitus

Tolba

Khashab

Said

2016

Int J Pharm Pharm Sci

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Objective: The aim of this study was is to investigate the proposed beneficial cardiovascular effects of a novel class of antidiabetic drugs named; dipeptidyl peptidase 4 inhibitors. In this study, we compared the effect of using add-on therapy of vildagliptin (dipeptidyl peptidase-4 inhibitor; DPP-4i) and gliclazide (sulphonylurea; SU) to that when using gliclazide monotherapy in patients with type 2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS) on different cardiovascular outcomes.Methods: A total of 60 patients diagnosed with T2DM, and ACS were randomly recruited into two treatment groups each of 30 patients to receive either gliclazide monotherapy (SU) or vildagliptin (DPP4i)+gliclazide (SU) add-on therapy, administered in a double-blind fashion. Outpatient visits were scheduled at 3, 6, and 12 mo where patient was reevaluated for cardiovascular (CV) outcomes and followed up for any arising cardiovascular complication. Results:The vildagliptin (DPP4i) plus gliclazide (SU) add-on therapy group have significantly shown more improved glycemic control, lipid profile and ventricular performance compared to gliclazide (SU) monotherapy group with p values<0.05. Conclusion:Vildagliptin as a DPP4i provides favourable cardiovascular effects beyond glucose control. Yet, its long-term safety and efficacy data still needs further investigations.

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Section: Discussionmentioning

confidence: 99%

Theeffect of Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Disease Risk in Type 2 Diabetes Mellitus

Tolba

Khashab

Said

2016

Int J Pharm Pharm Sci

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“…[1][2][3] Diabetic patients with heart failure have an increased mortality and an increased risk of hospitalisations and the use of certain anti-diabetic agents increase the risk of mortality and hospitalisation in heart failure. [4] Conversely, newer therapeutic agents have shown a significant reduction of mortality, morbidity and risk of developing heart failure in diabetic patients with proven cardiovascular disease. [5] Epidemiological evidence clearly shows that diabetes mellitus is independently associated with the risk of developing HF.…”

Section: Introductionmentioning

confidence: 99%

“…[4] Also, the adequate level of glucose control in diabetic patients with heart failure is under debate but higher levels of HbA1c should be recommended for diabetic patients with heart failure. [12] Treatment of heart failure in patients with diabetes…”

Section: Introductionmentioning

confidence: 99%

“…[21] In diabetic patients with heart failure a clear difference in the occurrence of adverse outcomes seems also to be related to the type of anti-diabetic medications as patients on drugs with a low risk of hypoglycaemia seem to have a better prognosis than those on medications known to be associated with a high risk of hypoglycaemia risk (secretagogues or insulin). [4,14] Treatment of diabetes in patients with heart failure…”

Section: Introductionmentioning

confidence: 99%

“…An increased risk of worsening heart failure has been reported with sulphonylureas in diabetic patients but has never been proven in prospective randomised clinical trials. [4] Therefore, sulphonylureas should be used with caution in diabetic patients with heart failure.…”

Section: Introductionmentioning

confidence: 99%

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The Management of Diabetic Patients with Heart Failure

Rosano¹,

Seferović²

2017

ICFJ

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Patients with diabetes mellitus have an increased risk of developing heart failure and diabetes mellitus is highly prevalent amongst patients with heart failure, especially those with HFpEF. Diabetic patients with heart failure have an increased mortality and an increased risk of hospitalisations and the use of certain anti- diabetic agents increase the risk of mortality and hospitalisation in heart failure. Conversely, newer therapeutic agents have shown a significant reduction of mortality, morbidity and risk of developing heart failure in diabetic patients with proven cardiovascular disease. This highly important area is reviewed in this paper.

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The Safety of Dipeptidyl Peptidase 4 Inhibitors and the Risk for Heart Failure

Scirica

2016

JAMA Cardiol

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In 2008, the Food and Drug Administration proposed a 2-step process for the approval of oral glucose-lowering therapies for type 2 diabetes that included an initial approval contingent on effective hemoglobin A 1c reduction and then a postmarketing cardiovascular outcomes trial with predefined end points, longer follow-up, and a higher risk population to demonstrate "noninferiority" to placebo. Incretin-based therapies were the first drugs to be evaluated under the new guidance policy. Glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide are incretin hormones secreted from the small intestine after meals and lower glucose levels by increasing β-cell insulin secretion, decreasing glucagon release, improving satiety, and slowing gut motility. Glucagon-like peptide-1 is rapidly deactivated by the enzyme dipeptidyl peptidase 4 (DPP4). The incretin axis can be pharmacologically enhanced either through injections of GLP-1 mimetics to achieve supraphysiologic levels or by inhibition of DPP4, which prolongs the half-life of physiologic levels of GLP-1, thus prolonging its action, although to a lesser extent than exogenous GLP-1 agonist. In preclinical experiments, both GLP-1 agonists and DPP4 inhibitors promoted nonglycemic-mediated cardioprotective actions. 1 There were no signals of any cardiovascular harm in any of the incretin-based clinical development programs and, in fact, there were data to suggest direct cardioprotective and vasculoprotective benefits. 2 To date, 3 DPP4 inhibitors (saxagliptin, 3 alogliptin, 4 and sitagliptin 5) and 1 GLP-1 agonist (lixisenatide 6) have published the primary results of their cardiovascular outcomes trials. On balance, the studies were more similar than different. Two studies enrolled patients following an acute coronary syndrome, 4,6 while the other 2 enrolled stable patients of whom most had established cardiovascular disease. 3,5 The primary results of the trials were also similar. Each easily met the noninferiority boundary with an upper bound of the 95% CI well below 1.3 for their primary and secondary composite end points. In fact, the event curves of each trial seemed to intertwine and the hazard ratios all fell within a few hundredths of a decimal point of 1.00. These safety data alone in almost 43 000 patients with type 2 diabetes are an important advance in understanding the cardiovascular risk profile of drugs to treat diabetes. Among the different trial results, the most unexpected finding was a 27% increased relative risk of hospitalization for

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Risk of hospitalization for heart failure in patients with type 2 diabetes newly treated with DPP-4 inhibitors or other oral glucose-lowering medications: a retrospective registry study on 127,555 patients from the Nationwide OsMed Health-DB Database

Abstract: In a very large observational study, the use of DPP-4i was associated with a reduced risk of HHF when compared with sulphonylureas.

Cited by 97 publications

References 29 publications

Theeffect of Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Disease Risk in Type 2 Diabetes Mellitus

Theeffect of Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Disease Risk in Type 2 Diabetes Mellitus

The Management of Diabetic Patients with Heart Failure

The Safety of Dipeptidyl Peptidase 4 Inhibitors and the Risk for Heart Failure

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