References of "SCHEEN, André"
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See detailMetabolic effects of SGLT-2 inhibitors beyond increased glucosuria: A review of the clinical evidence.
Scheen, André ULg; Paquot, Nicolas ULg

in Diabetes & metabolism (2014), 40(6 Suppl 1), 4-11

Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin) are new glucose-lowering agents that exert their therapeutic activity independently of insulin by ... [more ▼]

Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin) are new glucose-lowering agents that exert their therapeutic activity independently of insulin by facilitating glucose excretion through the kidneys. However, this simple renal mechanism that results in sustained glucose urinary loss leads to more complex indirect metabolic effects. First, by reduction of chronic hyperglycaemia and attenuation of glucose toxicity, SGLT-2 inhibitors can improve both insulin secretion by beta cells and peripheraltissue insulin sensitivity. In the case of canagliflozin, because of low-potency SGLT1 inhibition, a non-renal (intestinal) effect may also be considered, which may contribute to better control of postprandial hyperglycaemia, although this contribution remains to be better analyzed in humans. Second, chronic glucose loss most probably leads to compensatory mechanisms. One of them, although not well evidenced in humans, might involve an increase in energy intake, an effect that may limit weight loss in the long run. Another could be an increase in endogenous glucose production, most probably driven by increased glucagon secretion, which may somewhat attenuate the glucoselowering effect. Nevertheless, despite these compensatory mechanisms and most probably because of the positive effects of the reduction in glucotoxicity, SGLT-2 inhibitors exert clinically relevant glucose-lowering activity while promoting weight loss, a unique dual effect among oral antidiabetic agents. Furthermore, the combination of SGLT-2 inhibitors with other drugs that either have anorectic effects (such as incretin-based therapies) or reduce hepatic glucose output (like metformin) and, thus, may dampen these two compensatory mechanisms appears appealing for the management of type 2 diabetes mellitus. [less ▲]

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See detailEditorial. SGLT-2 receptor inhibitors: An opportunity to revise our therapeutic strategy for type 2 diabetes?
Bonnet, Fabrice; Scheen, André ULg

in Diabetes & metabolism (2014), 40(6 Suppl 1), 1-3

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See detailEditorial. SGLT-2 receptor inhibitors: An opportunity to revise our therapeutic strategy for type 2 diabetes?
Bonnet, Fabrice; Scheen, André ULg

in Diabetes & metabolism (2014), 40(6 Suppl 1), 1-3

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See detailEditorial. SGLT-2 receptor inhibitors: An opportunity to revise our therapeutic strategy for type 2 diabetes?
Bonnet, Fabrice; Scheen, André ULg

in Diabetes & metabolism (2014), 40(6 Suppl 1), 1-3

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See detailEditorial. SGLT-2 receptor inhibitors: An opportunity to revise our therapeutic strategy for type 2 diabetes?
Bonnet, Fabrice; Scheen, André ULg

in Diabetes & metabolism (2014), 40(6 Suppl 1), 1-3

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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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See detailBien gerer les couts des soins de sante aux personnes agees: un des defis majeurs'pour le 21(eme) siecle.
Scheen, André ULg; Petermans, Jean ULg

in Revue medicale de Liege (2014), 69(5-6), 229-32

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See detailMaladies hepatiques chroniques et diabete.
Jaafar, Jaafar; de Kalbermatten, Benedicte; Philippe, Jacques et al

in Revue medicale suisse (2014), 10(433), 12541256-60

The presence of chronic liver diseases may drastically limit the use of anti-diabetic drugs. Chronic liver diseases increase insulin resistance, and in some risk groups promote the development of diabetes ... [more ▼]

The presence of chronic liver diseases may drastically limit the use of anti-diabetic drugs. Chronic liver diseases increase insulin resistance, and in some risk groups promote the development of diabetes. Therefore, antidiabetic treatment should be adapted to the severity of liver disease. However, diabetes, notably when associated with obesity and dyslipidemia, participates in the development of nonalcoholic fatty liver disease and to steato-hepatitis that may progress to cirrhosis and hepatocellular carcinoma. Other relations between diabetes and chronic liver disease will be discussed in this article. Finally, the indications and limits of each anti-diabetic therapy group will be discussed according to the degree of liver damage. [less ▲]

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See detailPharmacokinetics in patients with chronic liver disease and hepatic safety of incretin-based therapies for the management of type 2 diabetes mellitus.
Scheen, André ULg

in Clinical pharmacokinetics (2014), 53(9), 773-85

Patients with type 2 diabetes mellitus have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis, and about one-third of cirrhotic patients have ... [more ▼]

Patients with type 2 diabetes mellitus have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis, and about one-third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents, such as metformin and sulphonylureas, may be a concern in case of hepatic impairment (HI). New glucose-lowering agents targeting the incretin system are increasingly used for the management of type 2 diabetes. Incretin-based therapies comprise oral inhibitors of dipeptidyl peptidase-4 (DPP-4) (gliptins) or injectable glucagon-like peptide-1 (GLP-1) receptor agonists. This narrative review summarises the available data regarding the use of both incretin-based therapies in patients with HI. In contrast to old glucose-lowering agents, they were evaluated in specifically designed acute pharmacokinetic studies in patients with various degrees of HI and their hepatic safety was carefully analysed in large clinical trials. Only mild changes in pharmacokinetic characteristics of DPP-4 inhibitors were observed in patients with different degrees of HI, presumably without major clinical relevance. GLP-1 receptor agonists have a renal excretion rather than liver metabolism. Specific pharmacokinetic data in patients with HI are only available for liraglutide. No significant changes in liver enzymes were reported with DPP-4 inhibitors or GLP-1 receptor agonists, alone or in combination with various other glucose-lowering agents, in clinical trials up to 2 years in length. On the contrary, preliminary data suggested that incretin-based therapies may be beneficial in patients with CLD, more particularly in the presence of non-alcoholic fatty liver disease. Nevertheless, caution should be recommended, especially in patients with advanced cirrhosis, because of a lack of clinical experience with incretin-based therapies in these vulnerable patients. [less ▲]

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See detailL'alogliptine (Vipidia): inhibiteur selectif de la DPP-4 avec une bonne securite cardiovasculaire.
Scheen, André ULg

in Revue medicale de Liege (2014), 69(7-8), 460-6

Alogliptin (Vipidia) is a new selective inhibitor of dipeptidyl peptidase-4. By potentiating insulin secretion and by inhibiting glucagon secretion, both in a glucose-dependent manner, it improves glucose ... [more ▼]

Alogliptin (Vipidia) is a new selective inhibitor of dipeptidyl peptidase-4. By potentiating insulin secretion and by inhibiting glucagon secretion, both in a glucose-dependent manner, it improves glucose control of type 2 diabetic patients, without increasing the risk of hypoglycaemia and inducing weight gain, with an excellent clinical and biological tolerance. Both efficacy and safety have been demonstrated in randomised controlled trials, in monotherapy or in combination with other oral antidiabetic agents or even insulin. These results were obtained independently of clinical or demographic patient characteristics, including in elderly subjects and in patients with renal insufficiency. However, because alogliptin is eliminated through the kidneys, the usual dose of 25 mg once daily should be reduced to 12.5 mg per day in case of moderate renal impairment and to 6.25 mg per day in case of severe renal failure. Cardiovascular safety of alogliptin has been demonstrated in a large prospective study (EXAMINE) showing non-inferiority versus placebo in type 2 diabetic patients following an acute coronary syndrome. [less ▲]

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See detailLe diabete du sujet age: du defi epidemiologique a une approche personnalisee.
Scheen, André ULg; Paquot, Nicolas ULg; Bauduceau, B.

in Revue medicale de Liege (2014), 69(5-6), 323-8

Diabetes mellitus is a common chronic disease in the elderly, being either a known disease with a long history (type 1 or even more often type 2 diabetes) and then frequently associated with various ... [more ▼]

Diabetes mellitus is a common chronic disease in the elderly, being either a known disease with a long history (type 1 or even more often type 2 diabetes) and then frequently associated with various diabetic complications, or a recently diagnosed diabetes that may, however, have been ignored for a rather long time. In this latter case, diabetes may present as the occurrence or aggravation of one or several geriatric syndromes that overall result in a loss of autonomy. The global geriatric assessment, the estimation of life expectancy and the justification of glucose-lowering treatments should be performed at regular intervals in elderly diabetic people as they determine the right choice of glucose target levels and the best selection of glucose-lowering agents. Medications that can induce hypoglycaemia should ideally be avoided, especially in the frailty older population. The benefit-risk ratio of the proposed therapies should be analyzed first, and then regularly reassessed because of a potentially rapidly progressing condition. The recommended approach is a tailored management of diabetes that should integrate the clinical, functional and psycho-social aspects of elderly individuals. [less ▲]

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See detailPharmacotherapie du sujet agee: primum non nocere!
Scheen, André ULg

in Revue medicale de Liege (2014), 69(5-6), 282-6

Elderly patients, having various chronic diseases, are generally exposed to polypharmacy that may lead to potential adverse events. The latter may be explained by pharmacokinetic and pharmacodynamic ... [more ▼]

Elderly patients, having various chronic diseases, are generally exposed to polypharmacy that may lead to potential adverse events. The latter may be explained by pharmacokinetic and pharmacodynamic particularities that render elderly individuals more vulnerable when exposed to certain medications. Recruitment of elderly patients in clinical trials is often limited, so that it is not always easy to determine the real benefit/risk ratio of pharmacotherapy in this population. Obviously, iatrogenicity is quite frequent. Therefore, in front of unexplained alterations of health status in an elderly individual, the physician should consider the possibility of a drug adverse effect. Because of this situation, the physician should envisage a reasonable drug prescription in an elderly patient. Especially, not only the initiation of drug therapy should be carefully analyzed, but also the opportunity to eventually stop a medication that may be useless or even dangerous. Rather polypharmacy per se, it is the inappropriate prescription that should be avoided in the elderly. [less ▲]

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See detailWhich incretin-based therapy for type 2 diabetes?
Scheen, André ULg

in Lancet (2014)

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See detailLe medicament du mois. Bydureon: premier agoniste des recepteurs du GLP-1 en une injection hebdomadaire (exenatide a liberation prolongee).
Scheen, André ULg

in Revue medicale de Liege (2014), 69(4), 214-9

Bydureon is a new galenic formulation (long-acting release) of exenatide, the first agonist of Glucagon-Like Peptide-1 (GLP-1) receptors having been commercialized for the management of type 2 diabetes ... [more ▼]

Bydureon is a new galenic formulation (long-acting release) of exenatide, the first agonist of Glucagon-Like Peptide-1 (GLP-1) receptors having been commercialized for the management of type 2 diabetes. The microsphere technology permits a prolonged absorption of exenatide from the subcutaneous depot, which allows one injection per week instead of two injections per day with the initial formulation of exenatide (Byetta). The clinical development programme DURATION showed that exenatide 2 mg once weekly more markedly reduces glycated haemoglobin (HbA(1c)), with a similar weight loss but a better digestive tolerance profile (less nausea and vomiting after treatment initiation), compared with the twice daily 10 microg exenatide. When compared to other glucose-lowering agents, once weekly exenatide is more efficacious than sitagliptin, pioglitazone or basal insulin (glargine or detemir), with the advantage of producing weight loss and lowering arterial blood pressure. It does not induce hypoglycaemia and does not necessarily require home blood glucose monitoring, two advantages compared with insulin therapy. Bydureon is currently only reimbursed in Belgium after failure of and in addition to metformin-sulfonylurea combination. [less ▲]

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See detailInflammation as a link between obesity, metabolic syndrome and type 2 diabetes
ESSER, Nathalie ULg; Legrand, Sylvie ULg; Piette, Jacques ULg et al

in Diabetes Research & Clinical Practice (2014)

It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic ... [more ▼]

It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic inflammatory markers are risk factors for the development of type 2 diabetes and its macrovascular complications. Adipose tissue, liver, muscle and pancreas are themselves sites of inflammation in presence of obesity. An infiltration of macrophages and other immune cells is observed in these tissues associated with a cell population shift from an anti-inflammatory to a pro-inflammatory profile. These cells are crucial for the production of pro-inflammatory cytokines, which act in an autocrine and paracrine manner to interfere with insulin signaling in peripheral tissues or induce β-cell dysfunction and subsequent insulin deficiency. Particularly, the pro-inflammatory interleukin-1β is implicated in the pathogenesis of type 2 diabetes through the activation of the NLRP3 inflammasome. The objectives of this review are to expose recent data supporting the role of the immune system in the pathogenesis of insulin resistance and type 2 diabetes and to examine various mechanisms underlying this relationship. If type 2 diabetes is an inflammatory disease, anti-inflammarory therapies could have a place in prevention and treatment of type 2 diabetes. [less ▲]

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See detailLe temps de la reflexion... a propos de la demographie medicale et de la demographie "societale".
Scheen, André ULg

in Revue medicale de Liege (2014), 69(1), 1-3

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