References of "SCHEEN, André"
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See detailLe médicament du mois. Le dulaglutide (Trulicity®) : Nouvel agoniste des récepteurs du Glucagon-Like Peptide-1 en injection hebdomadaire pour traiter le diabète de type 2
SCHEEN, André ULg

in Revue Médicale de Liège (2016), 71

Summary : Dulaglutide (Trulicity®) is a new once-weekly agonist of Glucagon-Like Peptide-1 (GLP-1) receptors indicated in the treatment of type 2 diabetes. Phase III clinical trials in AWARD programme ... [more ▼]

Summary : Dulaglutide (Trulicity®) is a new once-weekly agonist of Glucagon-Like Peptide-1 (GLP-1) receptors indicated in the treatment of type 2 diabetes. Phase III clinical trials in AWARD programme demonstrated the efficacy and safety of dulaglutide in patients with type 2 diabetes treated by diet and exercise, metformin, a combination of metformin and a sulfonylurea or metformin and pioglitazone or even by supplements of prandial insulin. In the AWARD programme, dulaglutide (subcutaneous 0.75 or 1.5 mg once weekly) exerted a greater glucose-lowering activity than metformin, sitagliptin, exenatide or insulin glargine, and was non-inferior to liraglutide 1.8 mg once daily. Dulaglutide is currently reimbursed in Belgium after failure of and in combination with a dual oral therapy with metformin and a sulfonylurea or metformin and pioglitazone. [less ▲]

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See detailLa vignette diagnostique de l’étudiant. L’importance du facteur temps et de la chronologie des événements dans l’anamnèse médicale
SCHEEN, André ULg

in Revue Médicale de Liège (2016), 71

Summary : Medical history taking represents a key step in the diagnostic approach. A structured interview with a special attention to the chronology of events is mandatory. The medical student often fails ... [more ▼]

Summary : Medical history taking represents a key step in the diagnostic approach. A structured interview with a special attention to the chronology of events is mandatory. The medical student often fails to use the information on time in an optimal way. The aim of this article is to draw the attention on a few key elements, especially the age of the patient, the duration of symptoms, the time of occurrence of complaints within the 24h period and, finally, how to interpret the simultaneous or sequential occurrence of two (or more) events. [less ▲]

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See detailLe médicament du mois. Insuline glargine 300 U/mL (Toujeo®)
SCHEEN, André ULg

in Revue Médicale de Liège (2016), 71

Summary : This article presents a new formulation of insulin glargine concentrated at 300 U/mL (Gla-300). It is commercialized under the trade name of Toujeo® in an optimized pre-filled SoloStar™ pen for ... [more ▼]

Summary : This article presents a new formulation of insulin glargine concentrated at 300 U/mL (Gla-300). It is commercialized under the trade name of Toujeo® in an optimized pre-filled SoloStar™ pen for the treatment of type 1 and type 2 diabetes in adults. Besides a threefold higher concentration compared to the classical insulin Lantus® (100 U/mL or Gla-100), both pharmacokinetic and pharmacodynamic profiles of Gla-300 are flatter and longer (more than 24 hours) and have a lesser intra-/inter-variability, which makes them more reproducible. Overall, Toujeo® offers the same hypoglycaemic efficacy and the same safety profile when compared with Lantus®. However, a lower risk of hypoglycaemia, especially at night, a slightly smaller weight gain and a better flexibility in the time of injection have been reported. The two insulin formulations are not bioequivalent and the daily insulin requirement is slightly higher with insulin Gla-300 than with insulin Gla-100. The shift from an already available basal insulin towards Toujeo® may require a dose adjustment and a reinforcement of blood glucose monitoring. [less ▲]

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See detailPossible survivorship bias rather than reverse causality in EMPA-REG OUTCOME.
Scheen, André ULg

in Diabetes Research & Clinical Practice (2016), (in press),

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See detailPharmacokinetic Characteristics and Clinical Efficacy of an SGLT2 Inhibitor Plus DPP-4 Inhibitor Combination Therapy in Type 2 Diabetes.
Scheen, André ULg

in Clinical Pharmacokinetics (2016)

Type 2 diabetes (T2D) generally requires a combination of several pharmacological approaches to control hyperglycaemia. Combining a sodium-glucose cotransporter type 2 inhibitor (SGLT2I, also known as ... [more ▼]

Type 2 diabetes (T2D) generally requires a combination of several pharmacological approaches to control hyperglycaemia. Combining a sodium-glucose cotransporter type 2 inhibitor (SGLT2I, also known as gliflozin) and a dipeptidyl peptidase-4 inhibitor (DPP-4I, also known as gliptin) appears to be an attractive strategy because of complementary modes of action. This narrative review analyzes the pharmacokinetics and clinical efficacy of different combined therapies with an SGLT2I (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, tofogliflozin) and DPP-4I (linagliptin, saxagliptin, sitagliptin, teneligliptin). Drug-drug pharmacokinetic interaction studies do not show any significant changes in peak concentrations (C max) and total exposure (area under the curve of plasma concentrations [AUC]) of either drug when they were administered together orally compared with corresponding values when each of them was absorbed alone. Two fixed-dose combinations (FDCs) are already available (dapagliflozin-saxagliptin, empagliflozin-linagliptin) and others are in development (ertugliflozin-sitagliptin). Preliminary results show bioequivalence of the two medications administered as FDC tablets when compared with coadministration of the individual tablets. Dual therapy is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin. SGLT2I and DPP-4I could be used as initial combination or in a stepwise approach. The additional glucose-lowering effect appears to be more marked when a gliflozin is added to a gliptin than when a gliptin is added to a gliflozin. Combining the two pharmacological options is safe and does not induce hypoglycaemia. [less ▲]

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See detailProgramme EDUDORA²: quelles leçons tirer de l'étude des représentations au sein de la triade patient/soignant/famille pour le traitement et la prévention du diabète et de l'obésité?
Degrange, Sophie ULg; Legrand, Catherine ULg; Pétré, Benoît ULg et al

in Etienne, Anne-Marie; Bragard, Isabelle (Eds.) Evolutions sociales, innovations et politiques. Nouveaux enjeux en psychologie de la santé (2016)

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See detailBody image discrepancy and subjective norm as mediators and moderators of the relationship between body mass index and quality of life
Pétré, Benoît ULg; Scheen, André ULg; ziegler, olivier et al

in Patient Preference and Adherence (2016), 10

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See detailReappraisal of the diuretic effect of empagliflozin in the EMPA-REG OUTCOME trial: Comparison with classic diuretics.
Scheen, André ULg

in Diabètes & Métabolism (2016)

AIMS: Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has been associated with a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes and ... [more ▼]

AIMS: Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has been associated with a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes and antecedents of cardiovascular disease. This effect was attributed to a diuretic (haemodynamic) rather than metabolic (antiatherogenic) effect. The aim of this review is to offer arguments that either support or challenge this 'diuretic hypothesis'. METHODS: The literature was scrutinized to: (1) examine the diuretic effects of SGLT2 inhibitors vs. hydrochlorothiazide as the reference diuretic; (2) analyze the effects of classic diuretics on cardiovascular outcomes and mortality in diabetic patients; and (3) reconsider some of the specific analyses of the EMPA-REG OUTCOME trial possibly related to a diuretic effect. RESULTS: The diuretic effect of empagliflozin has so far been poorly investigated, although SGLT2 inhibitors have actions distinct from those of classic diuretics. The effects of thiazide-like diuretics on cardiovascular and overall mortality have been limited in diabetic patients with hypertension, whereas the effects of mineralocorticoid receptor antagonists in subgroups of diabetic patients with heart failure were more impressive, but still largely inferior to those reported in EMPA-REG, where relative reductions in mortality with empagliflozin were observed in diabetic patients with or without heart failure, arterial hypertension, renal impairment or diuretic background therapy. CONCLUSION: Although the diuretic hypothesis was put forward to explain the remarkable reduction in mortality with empagliflozin in EMPA-REG, the available results do not support a major contribution of this mechanism, unless the specific diuretic effect of SGLT2 inhibitors turns out to be markedly different from those of classic diuretics. [less ▲]

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See detailEffects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME.
Scheen, André ULg

in Diabetes Research & Clinical Practice (2016), 121

Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of ... [more ▼]

Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of cardiovascular disease in the EMPA-REG OUTCOME trial. This effect has been attributed to a hemodynamic rather than a metabolic effect, partly due to the osmotic/diuretic effect of empagliflozin and to the reduction in arterial blood pressure. The present review will: (1) summarize the results of specific studies having tested the blood pressure lowering effects of SGLT2 inhibitors; (2) describe the results of meta-analyses of trials having evaluated the effects on mortality and cardiovascular outcomes of lowering blood pressure in patients with T2D, with a special focus on baseline and target blood pressures; (3) compare the cardiovascular outcome results in EMPA-REG OUTCOME versus other major trials with antihypertensive agents in patients with T2D; and (4) evaluate post-hoc analyses from EMPA-REG OUTCOME, especially subgroups of patients of special interest regarding the blood pressure lowering hypothesis. Although BP reduction associated to empagliflozin therapy may partly contribute to the benefits reported in EMPA-REG OUTCOME, other mechanisms most probably play a greater role in the overall CV protection and reduction in mortality observed in this trial. [less ▲]

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See detailSGLT2 Inhibitors: Benefit/Risk Balance.
Scheen, André ULg

in Current Diabetes Reports (2016), 16(10), 92

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycemia by increasing urinary glucose excretion. They have been evaluated in patients with type 2 diabetes treated with diet ... [more ▼]

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycemia by increasing urinary glucose excretion. They have been evaluated in patients with type 2 diabetes treated with diet/exercise, metformin, dual oral therapy or insulin. Three agents are available in Europe and the USA (canagliflozin, dapagliflozin, empagliflozin) and others are commercialized in Japan or in clinical development. SGLT2 inhibitors reduce glycated hemoglobin, with a minimal risk of hypoglycemia. They exert favorable effects beyond glucose control with consistent body weight, blood pressure, and serum uric acid reductions. Empagliflozin showed remarkable reductions in cardiovascular/all-cause mortality and in hospitalization for heart failure in patients with previous cardiovascular disease. Positive renal outcomes were also shown with empagliflozin. Mostly reported adverse events are genital mycotic infections, while urinary tract infections and events linked to volume depletion are rather rare. Concern about a risk of ketoacidosis and bone fractures has been recently raised, which deserves caution and further evaluation. [less ▲]

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See detailPrecision medicine: The future in diabetes care?
Scheen, André ULg

in Diabetes Research & Clinical Practice (2016), 117

Personalized medicine aims at better targeting therapeutic intervention to the individual to maximize benefit and minimize harm. Type 2 diabetes (T2D) is a heterogeneous disease from a genetic ... [more ▼]

Personalized medicine aims at better targeting therapeutic intervention to the individual to maximize benefit and minimize harm. Type 2 diabetes (T2D) is a heterogeneous disease from a genetic, pathophysiological and clinical point of view. Thus, the response to any antidiabetic medication may considerably vary between individuals. Numerous glucose-lowering agents, with different mechanisms of action, have been developed, a diversified armamentarium that offers the possibility of a patient-centred therapeutic approach. In the current clinical practice, a personalized approach is only based upon phenotype, taking into account patient and disease individual characteristics. If this approach may help increase both efficacy and safety outcomes, there remains considerable room for improvement. In recent years, many efforts were taken to identify genetic and genotype SNP's (Single Nucleotide Polymorphism's) variants that influence the pharmacokinetics, pharmacodynamics, and ultimately the therapeutic response of oral glucose-lowering drugs. This approach mainly concerns metformin, sulphonylureas, meglitinides and thiazolidinediones, with only scarce data concerning gliptins and gliflozins yet. However, the contribution of pharmacogenetics and pharmacogenomics to personalized therapy still needs to mature greatly before routine clinical implementation is possible. This review discusses both opportunities and challenges of precision medicine and how this new paradigm may lead to a better individualized treatment of T2D. [less ▲]

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See detailDiabetes: Time for reconciliation between cardiologists and diabetologists.
Scheen, André ULg

in Nature Reviews. Cardiology (2016)

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See detailDPP-4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects.
Scheen, André ULg

in Expert Opinion on Drug Metabolism & Toxicology (2016)

INTRODUCTION: Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycemia. Combining a dipeptidyl ... [more ▼]

INTRODUCTION: Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach. AREA COVERED: An extensive literature search was performed to analyze the pharmacokinetics, pharmacodynamics and clinical experience of different gliptin-gliflozin combinations. EXPERT OPINION: There is a strong rationale for combining a DPP-4i and a SGLT2i in patients with T2D because the two drugs exert different and complementary glucose-lowering effects. Dual therapy (initial combination or stepwise approach) is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin. Combining the two pharmacological options is safe and does not induce hypoglycemia. The additional glucose-lowering effect is more marked when a gliflozin is added to a gliptin than when a gliptin is added to a gliflozin. Two fixed-dose combinations (FDCs) are already available (saxagliptin-dapagliflozin and linagliptin-empagliflozin) and others are in current development. Bioequivalence of the two compounds given as FDC tablets was demonstrated when compared with coadministration of the individual tablets. FDCs could simplify the anti-hyperglycaemic therapy and improve drug compliance. [less ▲]

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See detailAssessment of cardiovascular risk of new drugs for the treatment of diabetes mellitus: risk assessment vs. risk aversion.
Zannad, Faiez; Stough, Wendy Gattis; Lipicky, Raymond J. et al

in European heart journal. Cardiovascular pharmacotherapy (2016), 2(3), 200-205

The Food and Drug Administration issued guidance for evaluating the cardiovascular risk of new diabetes mellitus drugs in 2008. Accumulating evidence from several completed trials conducted within this ... [more ▼]

The Food and Drug Administration issued guidance for evaluating the cardiovascular risk of new diabetes mellitus drugs in 2008. Accumulating evidence from several completed trials conducted within this framework raises questions as to whether requiring safety outcome studies for all new diabetes mellitus therapies remains justified. Given the burden of cardiovascular disease in patients with diabetes, the focus should shift towards cardiovascular outcome studies designed to evaluate efficacy (i.e. to determine the efficacy of a drug over placebo or standard care) rather than demonstrating that risk is not increased by a pre-specified safety margin. All stakeholders are responsible for ensuring that new drug approvals occur under conditions of appropriate safety and effectiveness. It is also a shared responsibility to avoid unnecessary hurdles that may compromise access to useful drugs and threaten the sustainability of health systems. It is critical to renew this debate so that stakeholders can collectively determine the optimal approach for developing new drugs to treat type 2 diabetes mellitus. [less ▲]

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See detailLE MEDICAMENT DU MOIS. Le liraglutide a la dose de 3 mg (Saxenda): indication dans le traitement de l'obesite.
Scheen, André ULg

in Revue Médicale de Liège (2016), 71(5), 256-61

Liraglutide is an analogue of Glucagon-Like Peptide-1 (GLP-1) already indicated under the trade name of Victoza for the treatment of type 2 diabetes, at usual doses of 1.2 or 1.8 mg as once daily ... [more ▼]

Liraglutide is an analogue of Glucagon-Like Peptide-1 (GLP-1) already indicated under the trade name of Victoza for the treatment of type 2 diabetes, at usual doses of 1.2 or 1.8 mg as once daily subcutaneous injection. It is henceforth indicated at a dose of 3.0 mg, also as once daily subcutaneous injection, for the treatment of obesity or overweight with comorbidities under the trade name of Saxenda, in combination with diet and exercise. Besides a specific action on the endocrine pancreas, mainly responsible for the antihyperglycaemic effect, liraglutide helps controlling appetite at the hypothamalic level. A specific programme of controlled trials (especially SCALE studies) demonstrated both efficacy and safety of the 3.0 mg dose of liraglutide in obese or overweight patients with various comorbidities. [less ▲]

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See detailCombinaison fixe atorvastatine-ezetimibe (Atozet(R)).
Scheen, André ULg

in Revue medicale de Liege (2016), 71(1), 47-52

Cardiovascular prevention in subjects at high or very high risk requires a drastic reduction in LDL cholesterol according to the concept "the lower, the better". The combination of an inhibitor of ... [more ▼]

Cardiovascular prevention in subjects at high or very high risk requires a drastic reduction in LDL cholesterol according to the concept "the lower, the better". The combination of an inhibitor of cholesterol synthesis and a selective inhibitor of intestinal absorption results in a complementary and synergistic LDL-lowering activity. Besides a first fixed combination ezetimibe-simvastatin (Inegy(R)), a new fixed combination is presented, Atozet(R) that combines atorvastatin and ezetimibe. Because atorvastatin is more potent than simvastatin, this novel fixed combination should facilitate reaching therapeutic goals in terms of LDL cholesterol amongst patients with severe hypercholesterolaemia and/or at high or very high cardiovascular risk. [less ▲]

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See detailEffect of rifampin on the disposition of brivaracetam in human subjects: further insights into brivaracetam hydrolysis.
Stockis, Armel; Watanabe, Shikiko; Scheen, André ULg et al

in Drug metabolism and disposition: the biological fate of chemicals (2016), 44(6), 792-799

Brivaracetam (BRV) is a high-affinity synaptic vesicle protein 2A ligand developed for the treatment of uncontrolled partial-onset seizures. The present Phase I open-label two-way crossover study was ... [more ▼]

Brivaracetam (BRV) is a high-affinity synaptic vesicle protein 2A ligand developed for the treatment of uncontrolled partial-onset seizures. The present Phase I open-label two-way crossover study was designed to assess the effect of rifampin on the pharmacokinetics of BRV and its hydroxy (BRV-OH); acid (BRV-AC); and hydroxy acid (BRV OHAC) metabolites. Twenty-six healthy subjects received BRV 150mg single oral dose, either alone or following 5 days of rifampin 600 mg/day. BRV and its metabolites were examined for their plasma profiles and urinary excretion. Pharmacokinetic modeling was developed to estimate the rate constants of the various metabolic routes. Parallel in vitro assays were conducted to characterize the hydrolysis of BRV to BRV-AC as well as to identify any potential effect of rifampin on the hydrolysis reaction. Rifampin did not significantly affect the maximum plasma concentration (Cmax) of BRV but decreased its area under the curve (AUC) by 45%. In addition, rifampin significantly increased the AUC of BRV-OH (+109%), decreased the AUC of BRV-AC (-53%), but had little effect on BRV-OHAC (-10%). In vitro assays showed that the major urinary metabolite BRV-AC (33% of the dose) was likely to be formed by amidase EC 3.5.1.4. In vitro data indicated that the enzyme was not significantly inhibited nor induced by rifampin. Modeling confirmed that all the observed changes in vivo were secondary to the induction of the CYP2C19-mediated hydroxylation of BRV to BRV-OH (3.7-fold increase in the rate constant). [less ▲]

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