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See detailPharmacokinetics and clinical evaluation of the alogliptin plus pioglitazone combination for type 2 diabetes.
Scheen, André ULiege

in Expert opinion on drug metabolism & toxicology (2015), 11(6), 1005-20

INTRODUCTION: Type 2 diabetes is a complex disease with multiple defects, which generally requires a combination of several pharmacological approaches to reach glucose control targets. A unique fixed-dose ... [more ▼]

INTRODUCTION: Type 2 diabetes is a complex disease with multiple defects, which generally requires a combination of several pharmacological approaches to reach glucose control targets. A unique fixed-dose combination combines a thiazolidinedione (pioglitazone) and a dipeptidyl peptidase-4 inhibitor (alogliptin). Area covered: An extensive literature search was performed to analyze the pharmacokinetics of pioglitazone and alogliptin when used separately and in combination as well as to summarize clinical and toxicological considerations about the combined therapy. Expert opinion: Pioglitazone, a potent insulin sensitizer, and alogliptin, an incretin-based agent that potentiates post-meal insulin secretion and reduces glucagon secretion, have complementary mechanisms of action. The clinical efficacy of a combined therapy is superior to any single therapy in patients treated with diet or with metformin (with or without sulphonylurea). These two drugs can be administered once daily, with or without a meal. No clinically relevant pharmacokinetic interactions between the two agents have been described and the fixed-dose combination has shown bioequivalence with alogliptin and pioglitazone given separately. Combining alogliptin with pioglitazone does not alter the safety profile of each compound. Weight gain observed with pioglitazone may be limited with the addition of alogliptin. The concern of an increased risk of heart failure remains to be better investigated. [less ▲]

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See detailFacteurs génétiques et risque de dysglycémie dans des familles de diabétiques de type 2: l’étude DESCENDANCE
Franc, S; Cauchi, S; Yengo, L et al

in Diabètes & Métabolism (2015, April), 41(s1), 10-35

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See detailA review of gliptins for 2014.
Scheen, André ULiege

in Expert opinion on pharmacotherapy (2015), 16(1), 43-62

Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) occupy an increasing place in the armamentarium of drugs used for the management of hyperglycaemia and offer new opportunities for a ... [more ▼]

Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) occupy an increasing place in the armamentarium of drugs used for the management of hyperglycaemia and offer new opportunities for a personalized medicine in patients with Type 2 diabetes. Areas covered: An updated review providing an analysis of available recent data with commercialized DPP-4 inhibitors, with a special focus on: differences between the various molecules, novelties regarding their mechanism of action, clinical efficacy in mono- and various combined therapies, comparison with other new therapies, efficacy-safety profile in at risk patients, concern about pancreatic safety, perspectives in cardiovascular prevention and, finally, a selection of remaining unanswered important questions for the clinician. Expert opinion: DPP-4 inhibitors offer various advantages when compared to other glucose-lowering agents. Despite they have been commercialized since a few years only, available data obtained in randomised controlled trials are of better quality compared to those available with ancient classical glucose-lowering agents, especially in more fragile populations such as elderly people, individuals with renal impairment or at high cardiovascular risk and patients at higher risk of hypoglycaemia. However, there remain uncertainties and controversies that should be resolved by further ongoing large prospective controlled trials and increasing clinical experience combined with a careful post-marketing surveillance. [less ▲]

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See detailActualisation 2015 des recommandations américaines et européennes pour le traitement du diabète de type 2
Scheen, André ULiege; Paquot, Nicolas ULiege

in Revue Médicale de Liège (2015), 70(3), 122-128

The strategy for the management of type 2 diabetes, summarized by a group of experts of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), has been ... [more ▼]

The strategy for the management of type 2 diabetes, summarized by a group of experts of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), has been updated early 2015. As in the previous position statement published in 2012, a patientcentered approach is recommended and the choice of the best medication, after failure of metformin monotherapy, should be based on the efficacy and safety profile of each pharmacological class. Besides sulfonylureas, thiazolidinediones (pioglitazone), DPP-4 inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists or basal insulin, another new possibility consists in the addition of an inhibitor of sodium-glucose cotransporters type 2 (gliflozin). Thus, the variety of possible triple therapies is increasing dramatically. Furthermore, when a basal insulin (with or without metformin) is not able to adequately control blood glucose, instead of intensifying insulin therapy (as recommended in 2012), new opportunities are available with the addition of a gliptin, a gliflozin or a GLP-1 receptor agonist in the updated 2015 version. A global integrated approach targeting all risk factors is recommended to reduce cardiovascular complications, with a special emphasis on life-style. [less ▲]

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See detailLe mot de la... Société francophone du diabète: Société francophone du diabète et Afrique francophone: une relation enrichissante à double sens
Scheen, André ULiege; Hadjadj, S.

in Médecine des Maladies Métaboliques (2015), 9(2), 113-114

[No abstract available]

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See detailAvant-propos Journée thématique 2015 de la Société francophone du diabète (SFD)
Scheen, André ULiege

in Médecine des Maladies Métaboliques (2015), 9(8), 731

[No abstract available]

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See detailInstauration et optimisation d'une insulinothérapie en médecine générale : InsuStar, une étude observationnelle prospective belge dans le diabète de type 2
Scheen, André ULiege; Mathieu, C.; Nobels, F.

in Revue Médicale de Liège (2015), 70(9), 423-431

Initiating or intensifying insulin therapy is often considered as a challenge in general practice. The observational prospective Belgian study InsuStar was performed in 2011-2013 among 150 representative ... [more ▼]

Initiating or intensifying insulin therapy is often considered as a challenge in general practice. The observational prospective Belgian study InsuStar was performed in 2011-2013 among 150 representative general practitioners, who were invited to initiate or intensify insulin therapy when necessary in 523 patients with type 2 diabetes (mean age : 65.5 years; mean HbA1c : 8.8 %). The initiation of insulin therapy (glargine in > 50 %) was justified by insufficient glycaemic control (96 %) and its intensification (replacement of insulin NPH or premixed insulins by insulin glargine, eventually with the addition of a short-acting insulin analogue) aimed at improving glucose control (58 %), avoiding hypoglycaemia (17 %) or both (17 %). After a follow up of 6 ± 1 months, HbA1c level decreased from 8.79% to 7.52% (-1.27 %; 95 % confidence interval : -1.43,-1.11; p<0.001). Overall 27.6 % of patients reached an HbA1c < 7% versus 5.9 % at inclusion (p<0.001), with rather few hypoglycaemia and a high physician confidence level regarding insulin therapy. These results should encourage general practitioners to initiate insulin therapy at an earlier stage and to intensify it when necessary in patients with insufficiently controlled type 2 diabetes. [less ▲]

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See detailUn nouveau florilege estival de cas cliniques.
Scheen, Andre ULiege

in Revue Médicale de Liège (2015), 70(7-8), 349-50

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See detailMédecine personnalisée : Nouveaux défis pour le praticien
Scheen, Andre ULiege

in Revue medicale de Liege (2015), 70(5-6), 242-6

The clinician has to cope with new advances in medicine. Traditional medicine, which is based upon pathophysiological reasoning and clinical experience, has been reinforced by evidence-based medicine ... [more ▼]

The clinician has to cope with new advances in medicine. Traditional medicine, which is based upon pathophysiological reasoning and clinical experience, has been reinforced by evidence-based medicine, which relies on levels of evidence provided by controlled clinical trials carried out on cohorts of patients. Since a few years, personalized medicine has been put at the forefront. A therapy tailored to every patient, if possible characterized by biomarkers, among which, since the achievement of the whole human genome sequencing, an increasing number of genetic markers. Personalized medicine should be used as a complement of traditional and evidence-based medicine. Physicians should progressively integrate this new strategy in their therapeutic approach. Hence, clinicians have to face new challenges as far as scientific knowledge, practical applications and physician-patient relationship are concerned. [less ▲]

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See detailQuels médecins pour quelle médecine?
Scheen, André ULiege

in Revue medicale de Liege (2015), 70(1), 1-4

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See detailInflammatory markers and cardiometabolic diseases.
ESSER, Nathalie ULiege; Paquot, Nicolas ULiege; Scheen, André ULiege

in Acta clinica Belgica (2015), 70(3), 193-9

OBJECTIVES: A growing body of evidence emerges that obesity, metabolic syndrome, type 2 diabetes and cardiovascular disease are intimately related to chronic inflammation. METHODS: A narrative review ... [more ▼]

OBJECTIVES: A growing body of evidence emerges that obesity, metabolic syndrome, type 2 diabetes and cardiovascular disease are intimately related to chronic inflammation. METHODS: A narrative review summarizing the most recent data of the literature describing the pathological implications of inflammation in obese patients with cardiometabolic disorders. RESULTS: Besides high-sensitive C-reactive protein, various circulating or in situ inflammatory markers have been identified, presumably reflecting the presence of inflammation in various key-organs (visceral adipose tissue, skeletal muscle, pancreatic islets, liver, intestine, arterial wall). Available data support the concept that targeting inflammation, not only reduces systemic inflammatory markers, but also improves insulin sensitivity and ameliorates glucose control in insulin-resistant patients, thus potentially reducing the risk of cardiovascular complications. CONCLUSION: These observations confirm the role of inflammation in cardiometabolic diseases and support the development of pharmacological strategies that aim at reducing inflammation, especially in patients with type 2 diabetes. [less ▲]

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See detailAntidiabetic agents: Potential anti-inflammatory activity beyond glucose control.
Scheen, André ULiege; ESSER, Nathalie ULiege; Paquot, Nicolas ULiege

in Diabetes & metabolism (2015)

A growing body of evidence is emerging to show that abdominal obesity, the metabolic syndrome, type 2 diabetes, cardiovascular disease and microvascular diabetic complications are intimately related to ... [more ▼]

A growing body of evidence is emerging to show that abdominal obesity, the metabolic syndrome, type 2 diabetes, cardiovascular disease and microvascular diabetic complications are intimately related to chronic inflammation. These observations pave the way to the development of new pharmacological strategies that aim to reduce silent inflammation. However, besides specific anti-inflammatory agents, glucose-lowering medications may also exert anti-inflammatory effects that could contribute to improved outcomes in diabetic patients. Most studies have used metformin, an AMP-activated protein kinase (AMPK) activator, and thiazolidinediones (TZDs), which act as peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists. Both pharmacological classes (considered insulin-sparing agents or insulin sensitizers) appear to have greater anti-inflammatory activity than insulin-secreting agents such as sulphonylureas or glinides. In particular, TZDs have shown the widest range of evidence of lowered tissue (visceral fat and liver) and serum inflammation. In contrast, despite reducing postprandial hyperglycaemia, the effect of alpha-glucosidase inhibitors on inflammatory markers appears rather modest, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) and glucagon-like peptide-1 (GLP-1) receptor agonists appear more promising in this respect. These incretin-based therapies exert pleiotropic effects, including reports of anti-inflammatory activity. No human data are available so far regarding sodium-glucose cotransporter type 2 (SGLT2) inhibitors. Although they may have indirect effects due to reduced glucotoxicity, their specific mode of action in the kidneys does not suggest systemic anti-inflammatory activity. Also, in spite of the complex relationship between insulin and atherosclerosis, exogenous insulin may also exert anti-inflammatory effects. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and potential anti-inflammatory effects related to intrinsic actions of the pharmacological class. Finally, it would also be of major clinical interest to define what role the anti-inflammatory effects of these glucose-lowering agents may play in the prevention of macrovascular and microvascular diabetic complications. [less ▲]

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See detailEffect of brivaracetam on CYP3A activity, measured by oral midazolam.
Stockis, Armel; Watanabe, Shikiko; Scheen, André ULiege

in Journal of clinical pharmacology (2015)

Brivaracetam is a synaptic vesicle protein 2A ligand in phase III development for epilepsy. A phase I, open-label, randomized study was conducted in 42 healthy male participants to assess the effect of ... [more ▼]

Brivaracetam is a synaptic vesicle protein 2A ligand in phase III development for epilepsy. A phase I, open-label, randomized study was conducted in 42 healthy male participants to assess the effect of brivaracetam on CYP3A activity using midazolam as a probe. Participants were randomized to oral brivaracetam 5, 50, or 150 mg/day from Day 8 to Day 14. A single oral dose (7.5 mg) of midazolam was administered on Days 1, 13, and 20, and full pharmacokinetic profiles were obtained. For all brivaracetam doses, the areas under the plasma concentration-time curves from 0 to infinity (AUCinf ) for midazolam and 1'-hydroxymidazolam were similar on Days 13 and 20 compared with Day 1. Following brivaracetam 150 mg/day, the Day 13/Day 1 AUCinf ratio (90% confidence interval) was 1.09 (0.97, 1.21) and 1.04 (0.93, 1.17) for midazolam and 1'-hydroxymidazolam, respectively. For the Day 20/Day 1 comparison, the corresponding AUCinf ratios were 1.10 (0.98, 1.23) and 1.07 (0.97, 1.18). Maximum midazolam plasma concentration was increased on both Day 13 and Day 20 vs. Day 1 but the relevance of this finding was unclear. This study indicates that brivaracetam up to 150 mg/day has no significant inducing or inhibiting effect on CYP3A activity. [less ▲]

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See detailRelations entre gain baro-réflexe et autres marqueurs de risque chez le patient diabétique de type 2
SCHEEN, André ULiege; MARCHAND, Monique ULiege; PHILIPS, Jean-Christophe ULiege

in Annales de Cardiologie et d'Angeiologie (2015), 64(s1),

André J. Scheen, Monique Marchand, Jean-Christophe Philips (1) (1) Service de Diabétologie, Nutrition et Maladies métaboliques, CHU Sart Tilman, Université de Liège, Liège, Belgique. Relations entre gain ... [more ▼]

André J. Scheen, Monique Marchand, Jean-Christophe Philips (1) (1) Service de Diabétologie, Nutrition et Maladies métaboliques, CHU Sart Tilman, Université de Liège, Liège, Belgique. Relations entre gain baro-réflexe et autres marqueurs de risque chez le patient diabétique de type 2 Relationships between baroreflex gain and other risk markers in patients with type 2 diabetes Objectifs : Le gain baro-réflexe (GBR) est un marqueur de la neuropathie autonome cardiovasculaire (NAC) qui s’avère plus discriminant que le classique R-R E/I ratio. Le but du travail est d’étudier les relations entre le GBR et d’autres marqueurs de risque comme la pression pulsée (PP) et la diminution du débit de filtration glomérulaire (DFG) chez le patient diabétique de type 2 (DT2). Méthodes : Au total, 64 patients DT2 ont été étudiés par enregistrement continu de la pression artérielle (PA) et de la fréquence cardiaque (FC) lors d’un test postural standardisé (test de «squatting» : 1min debout – 1min accroupi – 1min debout). GBR est calculé par la pente de la relation entre les espaces R-R et PA systolique lors du redressement. PP (PAS-PAD) est analysée pendant tout le test et par son augmentation durant l’accroupissement (delta PP). Le DFG est calculé par la formule MDRD avant et après un suivi moyen de 12±5 années. Résultats : Les patients ont été séparés en deux groupes en fonction de la valeur médiane du GBR : G1 (n=34) : </=1,36 msec/mm Hg (moyenne ± SD : 0,77±0,40) vs G2 (n=30) : >1,36 (3,05±0,35). Les sujets de G1 sont légèrement plus âgés (58±7 vs 54±8 ans; p=0,04), mais ont un sexe ratio, une durée du DT2, un taux d’HbA1c et des valeurs de PA comparables aux valeurs de G2. Les patients de G1 ont une FC de base plus élevée (88±15 vs 82±14 bpm; p=0,0462) et un DFG plus bas (79±19 vs 95±19 ml/min; p=0,0479). Si la PP en position debout est comparable (59±15 vs 54±15 mmHg; p=0,1983), elle devient plus élevée en position accroupie (73±18 vs 65±16 mmHg; p=0,0395) chez G1 que chez G2. Lors du redressement, la chute de PA moyenne est significativement plus importante (-46±12 vs -38±12 mmHg; p=0,0079), avec un retard à la récupération des valeurs de base (29±19 vs 21±19 sec; p=0,0107) et une tachycardisation moindre (17±8 vs 23±9 bpm; p=0,0359) chez G1. Par contre, la diminution du DFG durant le suivi est comparable chez G1 vs G2 (-13±21 vs -13±21 ml/min; p=0,8561). Conclusion : Un GBR abaissé, marqueur de la NAC, est associé à une PP élevée en position accroupie (un marqueur indirect de rigidité artérielle) et une diminution du DFG. Par contre, la seule valeur de GBR ne permet pas de prédire l’ampleur de la dégradation de la fonction rénale lors d’un suivi ultérieur de 12 années [less ▲]

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