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See detailAnti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease.
Esser, Nathalie ULg; Paquot, Nicolas ULg; Scheen, André ULg

in Expert opinion on investigational drugs (in press)

Introduction: There is a growing body of evidence to suggest that chronic silent inflammation is a key feature in abdominal obesity, metabolic syndrome, type 2 diabetes (T2DM) and cardiovascular disease ... [more ▼]

Introduction: There is a growing body of evidence to suggest that chronic silent inflammation is a key feature in abdominal obesity, metabolic syndrome, type 2 diabetes (T2DM) and cardiovascular disease (CVD). These observations suggest that pharmacological strategies, which reduce inflammation, may be therapeutically useful in treating obesity, type 2 diabetes and associated CVD. Area covered: The article covers novel strategies, using either small molecules or monoclonal antibodies. These strategies include: approaches targeting IKK-b-NF-kB (salicylates, salsalate), TNF-alpha (etanercept, infliximab, adalimumab), IL-1beta (anakinra, canakinumab) and IL-6 (tocilizumab), AMP-activated protein kinase activators, sirtuin-1 activators, mammalian target of rapamycin inhibitors and C-C motif chemokine receptor 2 antagonists. Expert opinion: The available data supports the concept that targeting inflammation improves insulin sensitivity and beta-cell function; it also ameliorates glucose control in insulin-resistant patients with inflammatory rheumatoid diseases as well in patients with metabolic syndrome or T2DM. Although promising, the observed metabolic effects remain rather modest in most clinical trials. The potential use of combined anti-inflammatory agents targeting both insulin resistance and insulin secretion appears appealing but remains unexplored. Large-scale prospective clinical trials are underway to investigate the safety and efficacy of different anti-inflammatory drugs. Further evidence is needed to support the concept that targeting inflammation pathways may represent a valuable option to tackle the cardiometabolic complications of obesity. [less ▲]

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

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 detailLe médicament du mois Canagliflozine (Invokana®) : inhibiteur des cotransporteurs rénaux sglt2 pour traiter le diabète de type 2
SCHEEN, André ULg

in Revue Médicale de Liège (2014), 69(12), 692-699

Canagliflozin is an inhibitor of sodium-glucose cotransporters type 2 (SGLT2) that are present in renal tubules. This specific insulin-independent mechanism promotes glucosuria, which results in a ... [more ▼]

Canagliflozin is an inhibitor of sodium-glucose cotransporters type 2 (SGLT2) that are present in renal tubules. This specific insulin-independent mechanism promotes glucosuria, which results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA1c). Furthermore, canagliflozin promotes weight loss and lowers arterial (mainly systolic) blood pressure. Its efficacy is decreased in patients with renal insufficiency and the treatment should be stopped if estimated glomerular filtration rate is below 45 ml/min/1.73 m². Both the efficacy and safety of canagliflozin have been investigated in 24 to 104-week controlled trials versus placebo or versus an active comparator (glimepiride or sitagliptin). The mean reduction in HbA1c averages 0.75% when added to other treatments, as compared to placebo. The 100 mg dose is as active as sitagliptin 100 mg while the 300 mg canagliflozin dose is even more efficacious. Adverse events are mostly mycotic genital infections and more rarely mild urinary tract infections. Caution is required in elderly patients and the risk of volume depletion should be checked (hypotension). Hypoglycaemia may occur only in patients already treated with an insulin-secreting agent or insulin. Canagliflozin is commercialized under the trade name Invokana®, at the doses of 100 mg and 300 mg once daily, for the treatment of type 2 diabetes. [less ▲]

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See detailComment je traite … Recommandations pour interrompre un traitement médicamenteux
SCHEEN, André ULg

in Revue Médicale de Liège (2014), 69(12), 644-649

L’interruption d’un traitement pharmacologique est une situation clinique fréquente qui peut paraître plus simple à gérer que l’instauration d’un nouveau traitement, mais qui impose néanmoins de remplir ... [more ▼]

L’interruption d’un traitement pharmacologique est une situation clinique fréquente qui peut paraître plus simple à gérer que l’instauration d’un nouveau traitement, mais qui impose néanmoins de remplir certaines conditions et de respecter certaines précautions : 1) pouvoir expliciter les raisons qui justifient l’arrêt du traitement; 2) vérifier qu’il n’y a pas de danger à interrompre le traitement (même si cette interruption est transitoire); 3) savoir comment gérer au mieux l’arrêt de la thérapeutique, en particulier choisir entre une interruption immédiate et une décroissance posologique progressive; et, enfin, 4) assurer un suivi approprié du patient dûment informé chez lequel le traitement vient d’être stoppé. [less ▲]

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See detailComment je traite … Recommandations pour surveiller et optimiser un traitement médicamenteux en cours
SCHEEN, André ULg

in Revue Médicale de Liège (2014), 69(11), 581-585

Any pharmacological treatment should ideally be effective and safe. The supervision of an ongoing therapy should control that individualized goals are reached while tolerance and safety are present. In ... [more ▼]

Any pharmacological treatment should ideally be effective and safe. The supervision of an ongoing therapy should control that individualized goals are reached while tolerance and safety are present. In case of not reaching the predefined objectives, the causes of failure should first be screened (for instance, exclusion of poor patient compliance), and the treatment should be then optimized : dose adjustment, add-on of another drug (if possible synergistic combination) and/or shift to a more effective pharmacological therapy. In some cases, therapeutic monitoring may be useful or even mandatory in order to better adjust drug dosing and thus guarantee both efficacy and safety. [less ▲]

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See detailLe médicament du mois Combinaison fixe périndopril-indapamide-amlodipine (Triplixam®) pour le traitement de l’hypertension artérielle
SCHEEN, André ULg; LANCELLOTTI, Patrizio ULg; KRZESINSKI, Jean-Marie ULg

in Revue Médicale de Liège (2014), 69(10), 565-570

Triplixam® is a fixed dose combination of three well known antihypertensive agents, with complementary activities, to control blood pressure in patients with arterial hypertension : perindopril, an ... [more ▼]

Triplixam® is a fixed dose combination of three well known antihypertensive agents, with complementary activities, to control blood pressure in patients with arterial hypertension : perindopril, an angiotensin converting enzyme inhibitor, indapamide, un diuretic whith thiazide-like effects but also specific properties, and amlodipine, a long-acting calcium antagonist of the dihydropyridine family. The potential synergic action allows better control of blood pressure with once daily administration, while limiting the incidence of adverse events. Various presentations with different dosages are available to facilitate individualized therapy. Warnings and precautions for use of every molecule should of course be respected. Such a fixed dose combination should contribute to limit clinical inertia and to improve therapeutic compliance. [less ▲]

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See detailComment je traite … recommandations pour instaurer un traitement medicamenteux
SCHEEN, André ULg

in Revue Médicale de Liège (2014), 69(10), 526-530

Initiating a new pharmacological therapy is an important step in the global medical approach. Such a decision is the final step of a careful reasoning and should respect some rules in order to guarantee ... [more ▼]

Initiating a new pharmacological therapy is an important step in the global medical approach. Such a decision is the final step of a careful reasoning and should respect some rules in order to guarantee the best efficacy, but also safety for the patient. Clinical inertia should be avoided, but the essential principles of the evidence based medicine should also be taken into account. This concise article summarizes the main fundamental rules and cautions that should be respected by any clinician when initiating a new pharmacological therapy. [less ▲]

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See detailComment je traite ... Le choix entre un sulfamide hypoglycémiant et une gliptine pour traiter le diabète de type 2
SCHEEN, André ULg

in Revue Médicale de Liège (2014), 69(9), 476-484

The pharmacological therapy of hyperglycaemia in type 2 diabetes becomes increasingly complex. After failure of metformin monotherapy, several choices are possible. In clinical practice, the most common ... [more ▼]

The pharmacological therapy of hyperglycaemia in type 2 diabetes becomes increasingly complex. After failure of metformin monotherapy, several choices are possible. In clinical practice, the most common dilemma is to choose between adding a sulphonylurea or adding a dipeptidyl peptidase-4 inhibitor (gliptin). This review analyses the arguments in favour of one or the other pharmacological option, based upon criteria of efficacy, tolerance, safety, easiness of use, use in at risk populations and, last but not least, cost of therapy. In general, a patient-centered approach is recommended with an individualization of the therapy in function of the characteristics of each patient with the aim to obtain the best benefits/risks ratio, at an affordable cost. [less ▲]

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See detailLes objectifs de la formation des soignants en Education Thérapeutique du Patient : une proposition
Pétré, Benoît ULg; Guillaume, Michèle ULg; LEGRAND, Catherine et al

Conference (2014, September)

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See detailFactors associated with clinical inertia: an integrative review
Aujoulat, I; Jacquemin, p; Rietzschel, E et al

in Advances in Medical Education and Practice (2014), 5

Failure to initiate or intensify therapy according to evidence-based guidelines is increasingly being acknowledged as a phenomenon that contributes to inadequate management of chronic conditions, and is ... [more ▼]

Failure to initiate or intensify therapy according to evidence-based guidelines is increasingly being acknowledged as a phenomenon that contributes to inadequate management of chronic conditions, and is referred to as clinical inertia. However, the number and complexity of factors associated with the clinical reasoning that underlies the decision-making processes in medicine calls for a critical examination of the consistency of the concept. Indeed, in the absence of information on and justification of treatment decisions that were made, clinical inertia may be only apparent, and actually reflect good clinical practice. This integrative review seeks to address the factors generally associated with clinical inaction, in order to better delineate the concept of true clinical inertia. [less ▲]

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See detailMetabolically healthy overweight and obesity
Esser, Nathalie ULg; SCHEEN, André ULg; PAQUOT, Nicolas ULg

in Annals of Internal Medicine (2014), 160(7), 514

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See detailQu'apportent les nouvelles recommandations américaines à propos de la prise en charge des dyslipidémies en prévention cardiovasculaire ? Comparaison avec les recommandations européennes et belges
Descamps, O; Rietzschel, E; Langlois, M et al

in Louvain Medical (2014), 133(1), 26-35

Les dernières recommandations américaines concernant la prise en charge des dyslipidémies en prévention cardiovasculaire ont soulevé de nombreuses questions par leurs différences avec nos approches ... [more ▼]

Les dernières recommandations américaines concernant la prise en charge des dyslipidémies en prévention cardiovasculaire ont soulevé de nombreuses questions par leurs différences avec nos approches habituelles. Entre autres, elles ont éradiqué la nécessité de « cible » de LDL-C à atteindre en fonction du niveau de risque cardiovasculaire et ont proposé plutôt une stratégie basée sur l’intensité de la réduction relative du LDL-C. L’examen critique et la comparaison des recommandations font apparaitre, toutefois, plus de similitudes que de différences, tout en encourageant à repenser certains aspects de notre pratique et à raviver notre motivation pour le plus grand bien des patients. [less ▲]

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See detailPharmacodynamics, Efficacy and Safety of Sodium-Glucose Co-Transporter Type 2 (SGLT2) Inhibitors for the Treatment of Type 2 Diabetes Mellitus.
Scheen, André ULg

in Drugs (2014)

Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries ... [more ▼]

Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries (dapagliflozin, canagliflozin, empagliflozin and ipragliflozin) and some others are in a late phase of development. The available SGLT2 inhibitors share similar pharmacokinetic characteristics, with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites, the absence of clinically relevant drug-drug interactions and a low renal elimination as parent drug. SGLT2 co-transporters are responsible for reabsorption of most (90 %) of the glucose filtered by the kidneys. The pharmacological inhibition of SGLT2 co-transporters reduces hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. The amount of glucose excreted in the urine depends on both the level of hyperglycaemia and the glomerular filtration rate. Results of numerous placebo-controlled randomised clinical trials of 12-104 weeks duration have shown significant reductions in glycated haemoglobin (HbA1c), resulting in a significant increase in the proportion of patients reaching HbA1c targets, and a significant lowering of fasting plasma glucose when SGLT2 inhibitors were administered as monotherapy or in addition to other glucose-lowering therapies including insulin in patients with T2DM. In head-to-head trials of up to 2 years, SGLT2 inhibitors exerted similar glucose-lowering activity to metformin, sulphonylureas or sitagliptin. The durability of the glucose-lowering effect of SGLT2 inhibitors appears to be better; however, this remains to be more extensively investigated. The risk of hypoglycaemia was much lower with SGLT2 inhibitors than with sulphonylureas and was similarly low as that reported with metformin, pioglitazone or sitagliptin. Increased renal glucose elimination also assists weight loss and could help to reduce blood pressure. Both effects were very consistent across the trials and they represent some advantages for SGLT2 inhibitors when compared with other oral glucose-lowering agents. The pharmacodynamic response to SGLT2 inhibitors declines with increasing severity of renal impairment, and prescribing information for each SGLT2 inhibitor should be consulted regarding dosage adjustments or restrictions in moderate to severe renal dysfunction. Caution is also recommended in the elderly population because of a higher risk of renal impairment, orthostatic hypotension and dehydration, even if the absence of hypoglycaemia represents an obvious advantage in this population. The overall effect of SGLT2 inhibitors on the risk of cardiovascular disease is unknown and will be evaluated in several ongoing prospective placebo-controlled trials with cardiovascular outcomes. The impact of SGLT2 inhibitors on renal function and their potential to influence the course of diabetic nephropathy also deserve more attention. SGLT2 inhibitors are generally well-tolerated. The most frequently reported adverse events are female genital mycotic infections, while urinary tract infections are less commonly observed and generally benign. In conclusion, with their unique mechanism of action that is independent of insulin secretion and action, SGLT2 inhibitors are a useful addition to the therapeutic options available for the management of T2DM at any stage in the natural history of the disease. Although SGLT2 inhibitors have already been extensively investigated, further studies should even better delineate the best place of these new glucose-lowering agents in the already rich armamentarium for the management of T2DM. [less ▲]

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See detailInteret d'une combinaison agoniste des recepteurs du GLP-1 et insuline basale dans le traitement du diabete de type 2.
Scheen, André ULg; Paquot, Nicolas ULg

in Revue medicale suisse (2014), 10(439), 1549-54

The complex pathophysiology of type 2 diabetes and its natural evolution, characterized by a progressive loss of glucose control due to the exhaustion of insulin secretion, lead to consider new ... [more ▼]

The complex pathophysiology of type 2 diabetes and its natural evolution, characterized by a progressive loss of glucose control due to the exhaustion of insulin secretion, lead to consider new complementary therapeutic options. Even at the insulin-requiring stage, the addition of a glucagon-like peptide-1 (GLP-1) receptor agonist is beneficial. Besides their incretinomimetic activity (which may decrease with the loss of beta-cell mass/function), GLP-1 receptor agonists reduce glucagon secretion, slow down gastric emptying and diminish appetite through a central effect. These combined effects permit to improve glucose control, while reducing daily insulin doses, together with less weight gain (or even weight loss) and generally less hypoglycaemia. Fixed insulin glargine-lixisenatide and insulin degludec-liraglutide are currently in development. [less ▲]

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See detailFaut-il mettre en doute les benefices du controle glycemique dans le diabete de type 2?
Scheen, André ULg

in Revue medicale suisse (2014), 10(439), 1531-2

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See detailDeficiences hormonales du sujet age: faut-il les traiter?
Racaru-Honciuc, Valentina; Betea, Daniela; Scheen, André ULg

in Revue medicale suisse (2014), 10(439), 1555-61558-61

Biological aging is characterized by a progressive loss of the secretion of various hormones, a phenomenon that leads some physicians to propose an anti-aging hormonal therapy. It is mandatory to ... [more ▼]

Biological aging is characterized by a progressive loss of the secretion of various hormones, a phenomenon that leads some physicians to propose an anti-aging hormonal therapy. It is mandatory to differentiate: 1) the physiological functional loss, which is a natural phenomenon without clear deleterious consequences on health and should not be compensated by the administration of hormones only to restore plasma levels similar to those measured in young people and 2) a pathological defect that deserves a replacement therapy to correct the endocrine deficiency and improve the health status of older individuals. This article considers the deficiencies in insulin, thyroid hormones, growth hormone, dehydroepiandrosterone (DHEA) and testosterone. For each hormone, a benefit/risk ratio of a so-called replacement therapy will be analyzed. [less ▲]

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See detailPharmacokinetics and Clinical Use of Incretin-Based Therapies in Patients with Chronic Kidney Disease and Type 2 Diabetes.
Scheen, André ULg

in Clinical pharmacokinetics (2014)

The prevalence of chronic kidney disease (CKD) of stages 3-5 (glomerular filtration rate [GFR] <60 mL/min) is about 25-30 % in patients with type 2 diabetes mellitus (T2DM). While most oral antidiabetic ... [more ▼]

The prevalence of chronic kidney disease (CKD) of stages 3-5 (glomerular filtration rate [GFR] <60 mL/min) is about 25-30 % in patients with type 2 diabetes mellitus (T2DM). While most oral antidiabetic agents have limitations in patients with CKD, incretin-based therapies are increasingly used for the management of T2DM. This review analyses (1) the influence of CKD on the pharmacokinetics of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists; and (2) the efficacy/safety profile of these agents in clinical practice when prescribed in patients with both T2DM and CKD. Most DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, alogliptin) are predominantly excreted by the kidneys. Thereby, pharmacokinetic studies showed that total exposure to the drug is increased in proportion to the decline of GFR, leading to recommendations for appropriate dose reductions according to the severity of CKD. In these conditions, clinical studies reported a good efficacy and safety profile in patients with CKD. In contrast, linagliptin is eliminated by a predominantly hepatobiliary route. As a pharmacokinetic study showed only minimal influence of decreased GFR on total exposure, no dose adjustment of linagliptin is required in the case of CKD. The experience with GLP-1 receptor agonists in patients with CKD is more limited. Exenatide is eliminated by renal mechanisms and should not be given in patients with severe CKD. Liraglutide is not eliminated by the kidney, but it should be used with caution because of the limited experience in patients with CKD. Only limited pharmacokinetic data are also available for lixisenatide, exenatide long-acting release (LAR) and other once-weekly GLP-1 receptor agonists in current development. Several case reports of acute renal failure have been described with GLP-1 receptor agonists, probably triggered by dehydration resulting from gastrointestinal adverse events. However, increasing GLP-1 may also exert favourable renal effects that could contribute to reducing the risk of diabetic nephropathy. In conclusion, the already large reassuring experience with DPP-4 inhibitors in patients with CKD offers new opportunities to the clinician, whereas more caution is required with GLP-1 receptor agonists because of the limited experience in this population. [less ▲]

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See detailAlogliptin: concern about hepatotoxicity?
Scheen, André ULg

in Clinical pharmacokinetics (2014), 53(11), 1057-9

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