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 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 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 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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See detailLe médicament du mois. Humalog® 200 U/ml KwikPenTM
SCHEEN, André ULg

in Revue Médicale de Liège (2015), 70

Summary : Insulin lispro (Humalog®) was the first short-acting insulin analogue to be indicated for the treatment of diabetes mellitus requiring insulin therapy. After subcutaneous injection, insulin ... [more ▼]

Summary : Insulin lispro (Humalog®) was the first short-acting insulin analogue to be indicated for the treatment of diabetes mellitus requiring insulin therapy. After subcutaneous injection, insulin lispro has a more favourable pharmacokinetics/pharmacodynamics profile than human insulin, characterized by a faster resorption and a more rapid and less prolonged glucose-lowering activity. These properties allow a better control of postprandial hyperglycaemia and a reduction of the risk of delayed hypoglycaemia, especially at night. The patient’s quality of life is also improved because insulin lispro can be injected within the 15 minutes before meal and even possibly after meal when the amount of food intake is unpredictable. Already commercialized as Humalog® 100 U/ml, insulin lispro is now also available as Humalog® 200 U/ml. A pharmacokinetics/pharmacodynamics study confirmed the bioequivalence of the two formulations, based upon the analysis of both plasma free insulin concentrations and glucose infusion rates to maintain normoglycaemia. Humalog® 200 U/ml is available in a novel disposable 3 ml pen (KwikPenTM), with lower glide force and injection volume; thus this new pen is more convenient for the patient compared with the current pen used to inject Humalog® 100 U/ml. The new formulation Humalog® 200 U/ml is indicated in Europe for adult patients with type 1 or type 2 diabetes who require more than 20 units of prandial insulin per day to cover their meals. [less ▲]

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See detailL’ÉTUDE CLINIQUE DU MOIS TECOS : confirmation de la sécurité cardiovasculaire de la sitagliptine
SCHEEN, André ULg; PAQUOT, Nicolas ULg

in Revue Médicale de Liège (2015), 70

Summary : The cardiovascular safety of sitagliptin has been evaluated in TECOS («Trial Evaluating Cardiovascular Outcomes with Sitagliptin»). TECOS recruited patients with type 2 diabetes and a history of ... [more ▼]

Summary : The cardiovascular safety of sitagliptin has been evaluated in TECOS («Trial Evaluating Cardiovascular Outcomes with Sitagliptin»). TECOS recruited patients with type 2 diabetes and a history of cardiovascular disease who received, as add-on to their usual therapy, either sitagliptin (n = 7.257) or placebo (n = 7.266), with a median follow-up of 3 years. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95 % confidence interval, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95 % CI, 0.83 to 1.20; P=0.98). The cardiovascular safety of sitagliptin, which was already shown in meta-analyses of phase II-III randomised controlled trials and in observational cohort studies in real life, is now confirmed in the landmark prospective cardiovascular outcome study TECOS. [less ▲]

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

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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