References of "SCHEEN, André"
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See detailRelations entre neuropathie autonome cardiaque (NAC), pression pulsée (PP) et insuffisance rénale chronique (IRC) chez le patient diabétique de type 2 (DT2)
PHILIPS, Jean-Christophe ULg; MARCHAND, Monique ULg; SCHEEN, André ULg

Poster (2016, March)

Objectifs : Ce travail étudie les relations entre trois complications diabétiques, la NAC, l’élévation de PP (marqueur de rigidité artérielle) et la diminution du débit de filtration glomérulaire (DFG ... [more ▼]

Objectifs : Ce travail étudie les relations entre trois complications diabétiques, la NAC, l’élévation de PP (marqueur de rigidité artérielle) et la diminution du débit de filtration glomérulaire (DFG) chez le patient DT2. Patients et méthodes : L’étude comprend 79 patients DT2 (53H/26F; 56±8 années; 11±8 années de DT2; IMC 28,4±4,6 kg/m²) analysés par enregistrement continu de la pression artérielle (PA) et de la fréquence cardiaque (appareil Finapres) lors d’un test postural standardisé. Le gain baro-réflexe (GBR, indice de NAC) correspond à la pente de la relation entre les espaces R-R et PA systolique (PAS) lors du redressement accroupi-debout. PP est analysée pendant tout le test et par son augmentation durant l’accroupissement (delta PP). DFG est estimé par la formule MDRD au début puis après un suivi moyen de 12±5 ans. Résultats : Les valeurs initiales sont : HbA1c : 8,8± 1,7%; DFG : 86±25 ml/min ; PP : 62±10 mmHg; BRG : 1,8±1,4 msec/mmHg. DFG est inversement corrélé à l’âge (r=-0,317; p=0,020), très positivement corrélé avec GBR (r=0,453; p=0,008), sans corrélation significative avec HbA1c (r=-0,023; p=0,935) ni avec PAS, PP ou encore delta PP (r=-0,206; p=0,114; NS). La diminution de DFG (-12±23 ml/min) lors du suivi de 12 ans n’a pu être corrélée de façon significative aux valeurs initiales et finales d’HbA1c, ni aux valeurs initiales de GBR (et d’autres marqueurs de NAC) ou de PA, même si la relation est proche de la signification pour delta PP (r=0,20; p=0,060). Conclusion : La forte relation initiale entre DFG et GBR suggère que IRC et NAC sont aggravées de façon conjointe et, possiblement, qu’une des deux complications influence l’autre. L’absence de toute corrélation entre la chute ultérieure de DFG et les autres paramètres initiaux peut s’expliquer par l’origine multifactorielle de la progression de l’IRC chez le patient DT2. [less ▲]

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See detailAntihyperglycémiants, antihypertenseurs et hypolipidémiants : comparaison des effets sur la mortalité et la morbidité cardiovasculaire chez le patient diabétique de type 2
SCHEEN, André ULg

Poster (2016, March)

Introduction : Réduire le risque de mortalité et morbidité cardiovasculaire (CV) chez le patient diabétique de type 2 (DT2) est primordial, mais les effets protecteurs semblent différents selon le mode ... [more ▼]

Introduction : Réduire le risque de mortalité et morbidité cardiovasculaire (CV) chez le patient diabétique de type 2 (DT2) est primordial, mais les effets protecteurs semblent différents selon le mode d’intervention pharmacologique étudié. Patients et méthodes : Les données de mortalité (totale et CV) et morbidité (infarctus du myocarde ou IDM, accidents vasculaires cérébraux ou AVC) rapportées (réduction du risque relatif) dans les essais ayant testé un traitement anti-hyperglycémiant sont comparées avec les résultats publiés dans deux méta-analyses concernant les hypolipidémiants et les anti-hypertenseurs consacrées au DT2. Résultats : Les antihypertenseurs réduisent les IDM (-12%) et la mortalité globale (-13%) de façon comparable, et diminuent davantage les AVC (-27%). Les hypolipidémiants diminuent davantage les IDM (- 22%) et les AVC (-21%) que la mortalité globale (-9%) (ou la mortalité CV : - 13%). Les données concernant les antihyperglycémiants diffèrent considérablement selon les médications testées. L’insuline et les sulfamides (UKPDS) réduisent plus les IDM (- 21%) que la mortalité totale (-8%), mais augmentent les AVC (+ 14%). La metformine (UKPDS) réduit, de façon comparable, les IDM (-39%), les AVC (-41%) et la mortalité totale (-36%). La pioglitazone (PROactive) diminue davantage les IDM (-17%) et les AVC (-19%) que la mortalité (-4%). Les gliptines (combinaison de SAVOR TIMI 53, EXAMINE, TECOS) ont montré des effets globalement neutres sur la mortalité totale (0%), les IDM (-2%) et les AVC (-1%). L’empagliflozine (EMPA-REG OUTCOME) se singularise par un effet favorable nettement plus marqué sur la mortalité totale (-32 %) et CV (- 38%) que sur les IDM (-13%) ou les AVC (+18%). Conclusion : Les discordances observées suggèrent l’implication de mécanismes protecteurs différents selon les interventions testées. EMPA-REG OUTCOME, le seul essai démontrant un effet plus marqué sur la mortalité que sur les événements CV, suggère un mécanisme propre de l’inhibiteur des SGLT2. [less ▲]

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See detailQuelle est la stratégie idéale pour traiter l’hyperglycémie du diabète de type 2 ?
SCHEEN, André ULg

in Médecine des Maladies Métaboliques (2016), 10(2), 91-93

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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 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 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 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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See detailReduction in cardiovascular and all-cause mortality in the EMPA-REG OUTCOME trial: A critical analysis.
SCHEEN, André ULg

in Diabetes & metabolism (2016), 42(2), 71-6

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See detailCreatinine-based equations for the adjustment of drug dosage in an obese population.
BOUQUEGNEAU, Antoine ULg; Vidal-Petiot, E; Moranne, O et al

in British Journal of Clinical Pharmacology (2016), 81(2), 349-361

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See detailWill delayed release metformin provide better management of diabetes type 2?
Scheen, André ULg

in Expert opinion on pharmacotherapy (2016), 17(5), 627-30

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See detailDulaglutide (LY-2189265) for the treatment of type 2 diabetes.
Scheen, André ULg

in Expert review of clinical pharmacology (2016), 9(3), 385-99

Dulaglutide is a new once-weekly glucagon-like peptide-1 receptor agonist for the management of hyperglycemia in adult patients with type 2 diabetes. It stimulates dose-dependent insulin secretion and ... [more ▼]

Dulaglutide is a new once-weekly glucagon-like peptide-1 receptor agonist for the management of hyperglycemia in adult patients with type 2 diabetes. It stimulates dose-dependent insulin secretion and reduces glucagon secretion, both in a glucose-dependent manner. Efficacy on blood glucose control and safety were demonstrated in the large AWARD program in type 2 diabetic patients treated with diet, metformin, dual oral therapy or insulin lispro with or without metformin, confirming findings of pilot studies in Caucasian patients and data in Japanese patients. Dulaglutide 1.5 mg once weekly was superior to metformin, sitagliptin, insulin glargine and exenatide twice daily, and non-inferior to liraglutide 1.8 mg once daily regarding the reduction in glycated hemoglobin. A modest but significant weight loss was consistently observed. Most frequent adverse events were transient and generally mild gastrointestinal disturbances. Clinical outcomes of dulaglutide will not be known until the large prospective cardiovascular outcome trial REWIND is complete. [less ▲]

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See detailInvestigational insulin secretagogues for type 2 diabetes.
SCHEEN, André ULg

in Expert opinion on investigational drugs (2016), 25(4), 405-22

INTRODUCTION: Insulin secretory defects are a key feature in the pathophysiology of type 2 diabetes (T2D). Classical insulin-secreting agents such as sulfonlyureas stimulate insulin secretion independent ... [more ▼]

INTRODUCTION: Insulin secretory defects are a key feature in the pathophysiology of type 2 diabetes (T2D). Classical insulin-secreting agents such as sulfonlyureas stimulate insulin secretion independent of glucose and cause hypoglycemia. Despite the advantages offered by incretin-based therapies, there is still a medical need for developing new insulin secretagogues for treating T2D. AREA COVERED: This article discusses: the new advances in the field of incretin-based therapies, glucokinase (GK) activators, free fatty acid receptor (FFAR) or G protein-coupled receptor (GPR) agonists (GPR40, GPR119, GPR120), imeglimin and some other insulin secretagogues with diverse mechanisms of action still in preclinical development. EXPERT OPINION: New insulin secretagogues should offer major advantages over sulfonylureas and gliptins. The challenge is to avoid uncontrolled insulin secretion and minimize the risk of hypoglycemia, to protect cells from progressive loss of mass and function for a better durability of glucose control, and to offer a good safety profile. Numerous approaches are in development. However, it is too early to decide whether one new pharmacological class will emerge as a clinically useful insulin secretagogue in the near feature. [less ▲]

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See detailInsulinosensibilisateurs (metformine/glitazones) : niveau de preuve et controverse
SCHEEN, André ULg

in Médecine des Maladies Métaboliques (2015), 9

Summary Because of the deleterious role attributed to insulin resistance, insulin sensitizing agents should theoretically reduce the incidence of cardiovascular complications in type 2 diabetes. In the ... [more ▼]

Summary Because of the deleterious role attributed to insulin resistance, insulin sensitizing agents should theoretically reduce the incidence of cardiovascular complications in type 2 diabetes. In the UKPDS, metformin reduced the risk of myocardial infarction and cardiovascular mortality in a rather small group of recently diagnosed patients at a low cardiovascular risk. These results deserve confirmation in a larger study with patients a high cardiovascular risk. Glitazones, as more specific insulin sensitizers, raised much hope. However, rosiglitazone fell from its pedestal after the suspicion of an increased risk of myocardial infarction. In PROactive among patients at high cardiovascular risk, pioglitazone gave positive but questionable results: statistical significance was not reached regarding the large composite primary endpoint, but well regarding the prespecified more focused principal secondary endpoint or in various post-hoc analyses. Thus, even if data with insulin sensitizers appear globally rather promising, evidence is rather weak, therefore leading to recurrent controversy. [less ▲]

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See detailComment je traite ... A propos du positionnement des inhibiteurs de la DPP-4 (gliptines) dans le traitement du diabète de type 2
SCHEEN, André ULg

in Revue Médicale de Liège (2015), 70

Summary : Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are more and more prominent medications in the management of type 2 diabetes (T2D), with five molecules commercialized and as many fixed-dose ... [more ▼]

Summary : Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are more and more prominent medications in the management of type 2 diabetes (T2D), with five molecules commercialized and as many fixed-dose combinations with metformin. After failure of metformin monotherapy, gliptins compete with old medications such as sulphonylureas, on the one hand, or with new oral antidiabetic agents such as inhibitors of renal sodium-glucose cotransporters type 2 (SGLT2) (gliflozines), on the other hand. Another alternative is the use of an incretin mimetic (agonist of glucagon-like peptide-1 receptors, to be injected subcutaneously) rather than an incretin enhancer such as a gliptin, before considering insulin therapy. This article analyses the arguments in favour of DPP-4 inhibitors. We will mainly consider the use of gliptins in patients with recently diagnosed T2D, in elderly and frail patients and in those with chronic kidney disease. To illustrate the discussion, we will analyze the results of both interventional and observational studies with vildagliptin. Obviously, these various groups of patients represent a large proportion of T2D population. [less ▲]

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See detailL’ETUDE CLINIQUE DU MOIS EMPA-REG OUTCOME : L’empagliflozine réduit la mortalité chez le patient diabétique de type 2 à haut risque cardiovasculaire
SCHEEN, André ULg

in Revue Médicale de Liège (2015), 70

Summary : EMPA-REG OUTCOME is an international, prospective, placebo-controlled clinical trial investigating the cardiovascular outcomes of empagliflozin, an inhibitor of sodium-glucose cotransporters ... [more ▼]

Summary : EMPA-REG OUTCOME is an international, prospective, placebo-controlled clinical trial investigating the cardiovascular outcomes of empagliflozin, an inhibitor of sodium-glucose cotransporters type 2 (SGLT2), in patients with type 2 diabetes mellitus and known cardiovascular disease. The trial succeeded in reaching the primary objective of non-inferiority and, in addition, showed, after a median follow up of 3.1 years, a superiority of empagliflozin (10 or 25 mg/day) versus placebo as regards the primary composite cardiovascular endpoint (hasard ratio or HR = 0.86; 95% CI 0.74-0.99; P = 0.04), hospitalisations for heart failure (- 35 %), cardiovascular mortality (- 38 %) and all-cause mortality (- 32 %, each p< 0.001). The reduction in mortality appeared early (< 6 months) and concerned all subgroups, without any obvious heterogeneity. This reduction in mortality does not seem to be fully explained by the concomitant slight reductions in HbA1c, body weight, waist circumference, blood pressure and serum uric acid levels in the empagliflozin groups versus the placebo group. Finally, the tolerance and safety profile of empagliflozin was good, with only a moderate increase in benign mycotic genital infections, a well-known adverse event with SGLT2 inhibitors. The remarkable effects of empagliflozin in the EMPA-REG OUTCOME trial, especially on mortality, should modify the management of patients with type 2 diabetes and a high cardiovascular risk in a near future. [less ▲]

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