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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 ULiege

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 ULiege

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 detailEditorial: Comment faire face à ce monde empreint d'incertitude et d'inquiétude ?
Scheen, André ULiege

in Revue Médicale de Liège (2016), 71(1), 1-3

[No abstract available]

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See detailInstauration d'une insulinothérapie chez le patient diabétique de type 2 en médecine générale: Comparaison de l’étude belge InsuStar avec quelques études françaises et internationales
Scheen, André ULiege

in Médecine des Maladies Métaboliques (2016), 10(4), 334-340

Initiating insulin therapy is often considered as a challenge in general practice, thus leading to a delay in the shift to insulin. We compare the results of the observational prospective Belgian study ... [more ▼]

Initiating insulin therapy is often considered as a challenge in general practice, thus leading to a delay in the shift to insulin. We compare the results of the observational prospective Belgian study InsuStar with those of several French and international studies. In most studies, initiating insulin therapy is proposed in patients with glycated hemoglobin (HbA1c) around 9% (75 mmol/mol). The initiation of insulin therapy, in most cases using basal insulin (NPH, or glargine), is associated with a mean HbA1c reduction of about 1.5%, but only around one third of the patients reach a target HbA1c level <7% (53 mmol/mol), which should promote further intensification of treatment. The risk of hypoglycemia is low, and patient's acceptance of insulin injection is usually good. These results should encourage general practitioners to initiate insulin therapy at an earlier stage in patients with insufficiently controlled type 2 diabetes on oral agents. © 2016 Elsevier Masson SAS [less ▲]

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See detailÉditorial: Chirurgie métabolique versus traitement médical optimize dans la prise en charge du diabète de type 2?
Scheen, André ULiege

in Revue Médicale Suisse (2016), 12(527), 1355-1356

[No abstract available]

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See detailCibler la voie métabolique du cortisol comme action thérapeutique dans le diabète de type 2
Scheen, André ULiege

in Médecine des Maladies Métaboliques (2016), 10(8), 725-731

The 11ß-hydroxysteroid dehydrogenase type 1 (11βHSD1) enzyme promotes the local conversion from inactive cortisone to active cortisol. It may play a role in the pathophysiology of abdominal obesity and ... [more ▼]

The 11ß-hydroxysteroid dehydrogenase type 1 (11βHSD1) enzyme promotes the local conversion from inactive cortisone to active cortisol. It may play a role in the pathophysiology of abdominal obesity and the metabolic syndrome, both showing some similarities with the Cushing syndrome. Synthetic selective inhibitors of 11βHSD1 have been investigated in pilot studies in overweight/obese patients with type 2 diabetes or hypertension. Although some positive effects were observed, they were considered as too modest compared to what could be obtained with other available drugs. More recently, a reduction in liver steatosis was reported in overweight/obese non-diabetic patients. Whereas some early 11βHSD1 inhibitors have been abandoned, others are still in development, which demonstrates a persisting interest for this innovative therapeutic approach. © 2016 Elsevier Masson SAS [less ▲]

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See detailProtection cardiovasculaire du patient diabetique de type 2 : d'EMPA-REG OUTCOME a LEADER.
Scheen, André ULiege; Wallemacq, Caroline; Jandrain, Bernard et al

in Revue Médicale Suisse (2016), 12(527), 1370-1375

Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, an inhibitor of sodium-glucose type ... [more ▼]

Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, an inhibitor of sodium-glucose type 2 (SGLT2) cotransporters, in EMPA-REG OUTCOME, and liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) receptors, in LEADER, showed a significant reduction in major cardiovascular events (- 14 and - 13 %, respectively), cardiovascular mortality (- 38 and - 22 %, respectively) and all-cause mortality (- 32 and - 15 %, respectively). A lower progression of kidney disease and less renal events were also reported. The underlying protective mechanisms remain controverted as the discussion whether the benefits are specific to each medication or could be extended to other molecules of these two pharmacological classes. [less ▲]

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See detailEfficacite de trois techniques de chirurgie bariatrique chez des sujets obeses diabetiques de type 2.
Bessemans, Severine; Scheen, André ULiege

in Revue Médicale Suisse (2016), 12(527), 1378-1382

This retrospective work compares the efficacy of three procedures of bariatric surgery in obese patients with type 2 diabetes : gastric bypass (n = 22), sleeve gastrectomy (n = 18) and Magenstrasse & Mill ... [more ▼]

This retrospective work compares the efficacy of three procedures of bariatric surgery in obese patients with type 2 diabetes : gastric bypass (n = 22), sleeve gastrectomy (n = 18) and Magenstrasse & Mill gastroplasty (also known as reversible sleeve (n = 19). The three interventions result in a remarkable weight loss after one year, a better glycaemic control, with often a remission of diabetes, a reduction of blood pressure and an improvement of lipid profile, allowing an interruption or a dose reduction of concomitant medications. Overall, classical sleeve provides almost similar results as gastric bypass and appears slightly better than reversible sleeve. These results deserve confirmation in studies with more patients followed for a longer term. [less ▲]

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See detailCombinaison gliptine-gliflozine dans le traitement du diabete de type 2.
Scheen, André ULiege; Paquot, Nicolas ULiege

in Revue Médicale Suisse (2016), 12(527), 1384-1388

Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycaemia. Combining a dipeptidyl peptidase-4 ... [more ▼]

Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycaemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach because the two drugs exert different and potentially 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 hypoglycaemia. Two fixed-dose combinations (FDCs) are already available (saxagliptin-dapagliflozin and linagliptin-empagliflozin) and others are in current development. [less ▲]

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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 ULiege

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 ULiege; Legrand, Catherine ULiege; Pétré, Benoît ULiege 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 ULiege; Scheen, André ULiege; 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 ULiege

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 ULiege

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 ULiege

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 ULiege

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 ULiege

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 ULiege

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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