References of "Scheen, André"
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See detailL’exploration des perceptions relatives à l’excès de poids pour mieux comprendre les difficultés dans la prise en charge de l’obésité : une étude populationnelle exploratoire
Crutze, Céline ULiege; Pétré, Benoît ULiege; Dardenne, Nadia ULiege et al

in Revue d'Epidémiologie et de Santé Publique = Epidemiology and Public Health (2017), 65(3), 209-219

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See detailSafety update on dapagliflozin (DAPA) across the phase 2b/3 clinical trial program
Jabbour, Serge; Seufert, Jochen; SCHEEN, André ULiege et al

Poster (2017, June)

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See detailImpact of glucose-lowering therapies on risk of stroke in type 2 diabetes.
Bonnet, Fernand ULiege; Scheen, André ULiege

in Diabètes & Métabolism (2017)

Patients with type 2 diabetes (T2D) have an increased risk of stroke compared with people without diabetes. However, the effects of glucose-lowering drugs on risk of ischaemic stroke in T2D have been less ... [more ▼]

Patients with type 2 diabetes (T2D) have an increased risk of stroke compared with people without diabetes. However, the effects of glucose-lowering drugs on risk of ischaemic stroke in T2D have been less extensively investigated than in coronary heart disease. Some evidence, including the UKPDS, has suggested a reduced risk of stroke with metformin, although the number of studies is limited. Inhibition of the KATP channels increases ischaemic brain lesions in animals. This is in agreement with a recent meta-analysis showing an increased risk of stroke with sulphonylureas vs. various comparators as both mono- and combination therapy. Pioglitazone can prevent recurrence of stroke in patients with previous stroke, as already shown in PROactive, although results are less clear for first strokes. As for DPP-4 inhibitors, there was a non-significant trend towards benefit for stroke, whereas a possible increased risk of stroke with SGLT2 inhibitors-and in particular, empagliflozin in the EMPA-REG OUTCOME trial-has been suggested and requires clarification. Experimental results support a potential protective effect of GLP-1 receptor agonists against stroke that has, at least in part, been translated to clinical benefits in T2D patients in the LEADER and SUSTAIN-6 trials. Further interventional studies are now warranted to confirm the effects of glucose-lowering agents on risk of stroke in patients with T2D. In summary, the effects of antidiabetic drugs on risk of stroke appear to be heterogeneous, with some therapies (pioglitazone, GLP-1 receptor agonists) conferring possible protection against ischaemic stroke, other classes showing a neutral impact (DPP-4 inhibitors, insulin) and some glucose-lowering agents being associated with an increased risk of stroke (sulphonylureas, possibly SGLT2 inhibitors, high-dose insulin in the presence of insulin resistance). [less ▲]

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See detailInvestigational glucagon receptor antagonists in Phase I and II clinical trials for diabetes.
Scheen, André ULiege; Paquot, Nicolas ULiege; Lefèbvre, Pierre ULiege

in Expert Opinion on Investigational Drugs (2017), 26(12), 1373-1389

INTRODUCTION: Despite type 2 diabetes (T2D) being recognized as a bihormonal pancreatic disease, current therapies are mainly focusing on insulin, while targeting glucagon has been long dismissed. However ... [more ▼]

INTRODUCTION: Despite type 2 diabetes (T2D) being recognized as a bihormonal pancreatic disease, current therapies are mainly focusing on insulin, while targeting glucagon has been long dismissed. However, glucagon receptor (GCGr) antagonists are currently investigated in clinical trials. Area covered: Following a brief description of the rationale for antagonizing GCGr in T2D, lessons from GCGr knock-out mice and pharmacological means to antagonize GCGr, a detailed description of the main results obtained with GCGr antagonists in Phase I-II clinical trials is provided. The development of several small molecules has been discontinued, while new ones are currently considered as well as innovative approaches such as monoclonal antibodies or antisense oligonucleotides inhibiting GCGr gene expression. Their potential benefits but also limitations are discussed. Expert opinion: The proof-of-concept that antagonizing GCGr improves glucose control in T2D has been confirmed in humans. Nevertheless, some adverse events led to stopping the development of some of these GCGr antagonists. New approaches seem to have a better benefit/risk balance, although none has progressed to Phase III clinical trials so far. Pharmacotherapy of T2D is becoming a highly competitive field so that GCGr antagonists should provide clear advantages over numerous existing glucose-lowering medications before eventually reaching clinical practice. [less ▲]

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See detailDapagliflozin in patients with type 2 diabetes mellitus: A pooled analysis of safety data from phase IIb/III clinical trials.
Jabbour, Serge; Seufert, Jochen; Scheen, André ULiege et al

in Diabetes, Obesity & Metabolism (2017)

AIM: To evaluate the safety and tolerability of dapagliflozin, a highly selective sodium-glucose co-transporter-2 inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: Data were pooled ... [more ▼]

AIM: To evaluate the safety and tolerability of dapagliflozin, a highly selective sodium-glucose co-transporter-2 inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: Data were pooled from 13 placebo-controlled trials of up to 24 weeks' duration (dapagliflozin, n = 2360; placebo, n = 2295). Larger placebo-/comparator-controlled pools of 21 (</=208 weeks; dapagliflozin, n = 5936; control, n = 3403) and 30 trials (>/=12 weeks; dapagliflozin, n = 9195; control, n = 4629) assessed the rare adverse events (AEs) of diabetic ketoacidosis (DKA) and lower limb amputation, respectively. RESULTS: Over 24 weeks, the overall incidence of AEs and serious AEs (SAEs) was similar for dapagliflozin and placebo: 60.0% vs 55.7% and 5.1% vs 5.4%, respectively. Rates of hypoglycaemia, volume depletion AEs, urinary tract infections (UTIs) and fractures were balanced between the groups. Genital infections were more frequent with dapagliflozin (5.5%) vs placebo (0.6%) and renal function AEs occurred in 3.2% vs 1.8% of patients (the most common renal AE was decreased creatinine clearance: 1.1% vs 0.7%). In the 21-study pool, 1 SAE of DKA and 3 AEs of ketonuria/metabolic acidosis occurred with dapagliflozin vs none with control; estimated combined incidence for these events was 0.03% (95% confidence interval 0.010-0.089). In the 30-study pool, lower limb amputation occurred in 8 (0.1%) and 7 (0.2%) patients receiving dapagliflozin and control, respectively. CONCLUSION: The overall incidence rates of AEs and SAEs were similar in the dapagliflozin and placebo/control groups, including the incidence of hypoglycaemia, volume depletion, fractures, UTIs, amputations and DKA. Genital infections were more frequent with dapagliflozin than placebo. [less ▲]

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See detailPharmacological management of type 2 diabetes: what's new in 2017?
Scheen, André ULiege

in Expert Review of Clinical Pharmacology (2017)

INTRODUCTION: Novelties in the management of type 2 diabetes are dominated by the commercialisation of new glucose-lowering agents, which offer alternatives to older antidiabetic medications, and by the ... [more ▼]

INTRODUCTION: Novelties in the management of type 2 diabetes are dominated by the commercialisation of new glucose-lowering agents, which offer alternatives to older antidiabetic medications, and by the publication of several prospective placebo-controlled outcome trials, which demonstrated not only cardiovascular safety but also cardiovascular and renal protection with some new medications. Areas covered: Updates regarding the use of glucose-lowering agents are discussed from a clinical point of view. Some new viewpoints concern older antidiabetic agents such as metformin, sulfonylureas and glitazones whose benefit-risk balance has been revisited, especially in high risk patients. The recent data regarding DPP-4 inhibitors (gliptins) focused on the safety profile of this pharmacological class, including in patients with impaired renal function. The highlight concerns the cardiovascular (and renal) protection by some GLP-1 receptor agonists (liraglutide, semaglutide) and SGLT2 inhibitors (empagliflozin, canagliflozin) in patients with high cardiovascular risk. Finally, efficacy and safety of new combinations and advances in insulin therapy will be briefly discussed. Expert commentary: The recent data from randomized controlled trials, meta-analyses and observational real-life studies should trigger a revision of the algorithm for the treatment of hyperglycemia in type 2 diabetes, especially in patients with high cardiovascular and/or renal risk. [less ▲]

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See detailVignette therapeutique de l'etudiant. Quel medicament antidiabetique choisir chez un patient diabetique de type 2 avec insuffisance cardiaque ?
Scheen, André ULiege; Paquot, Nicolas ULiege

in Revue Médicale de Liège (2017), 72(9), 423-428

Heart failure is raising an increasing interest in patients with type 2 diabetes. Indeed, they combine different risk factors for this complication and they have time to develop it because they survive ... [more ▼]

Heart failure is raising an increasing interest in patients with type 2 diabetes. Indeed, they combine different risk factors for this complication and they have time to develop it because they survive longer due to a better prevention of atherothrombotic cardiovascular events. Beyond the classical therapy of heart failure, management should select the most suited glucose-lowering agents. Indeed, all do not have the same impact as some of them have proven their ability to reduce the risk of hospitalisation for heart failure whereas others are associated with an increased risk, either well proven or at least suspected. The aim of this clinical case is to discuss the use of glucose-lowering drugs in a patient with type 2 diabetes with or at risk to develop heart failure. [less ▲]

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See detailVignette therapeutique de l'etudiant Comment prescrire un medicament antidiabetique oral chez un patient diabetique de type 2 avec insuffisance renale ?
Scheen, André ULiege; Paquot, Nicolas ULiege

in Revue Médicale de Liège (2017), 72(10), 462-468

Patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) are increasingly numerous, especially in the elderly population. Surprisingly, this situation is often under-recognized or even ... [more ▼]

Patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) are increasingly numerous, especially in the elderly population. Surprisingly, this situation is often under-recognized or even neglected in clinical practice. Yet, most oral antidiabetic (OAD) agents have limitations in case of renal impairment, either because they require a dose reduction, or are contra-indicated mainly for safety reasons. This clinical case gives the opportunity to discuss the modalities of prescription and cautions to be taken when using most commonly prescribed OAD, metformin, insulin secretagogues (sulfonylureas, repaglinide), DPP-4 inhibitors (gliptins) and SGLT2 inhibitors, in a patient with T2D and CKD. [less ▲]

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See detailDapagliflozin and saxagliptin tablets for adults with type 2 diabetes.
Scheen, André ULiege

in Expert Review of Clinical Pharmacology (2017)

INTRODUCTION: Saxagliptin (a dipeptidyl peptidase-4 inhibitor, DPP-4i) and dapagliflozin (a sodium-glucose cotransporter type 2 inhibitor, SGLT2i) improve glucose control in type 2 diabetes (T2D) through ... [more ▼]

INTRODUCTION: Saxagliptin (a dipeptidyl peptidase-4 inhibitor, DPP-4i) and dapagliflozin (a sodium-glucose cotransporter type 2 inhibitor, SGLT2i) improve glucose control in type 2 diabetes (T2D) through different potentially complementary mechanisms, thus offering the opportunity for a combined therapy. Area covered: The characteristics of the saxagliptin/dapagliflozin combination are analysed, focusing on: 1) pharmacokinetic and pharmacodynamic properties; 2) efficacy and safety in phase III trials with concurrent and sequential add-on therapy; and 3) potential use in clinical practice, including in special populations (cardiovascular disease, heart failure, chronic kidney disease, elderly). Expert commentary: Conclusions drawn from clinical trials investigating combination with the separate drugs are considered to apply to the fixed-dose combination (FDC) that demonstrates bioequivalence. Dual saxagliptin/dapagliflozin therapy is more potent than either monotherapy and can be used as an initial combination or a stepwise sequential approach. Dual therapy is generally well tolerated and may be used in special populations, with some limitations because of the presence of dapagliflozin. However, the latter may offer some advantages because of multiple effects attributed to SGLT2i. The best place of this dual combination for the management of T2D and the profile of patients who will make the most of this combined therapy remains to be defined. [less ▲]

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See detailProtection cardio-renale par les inhibiteurs des SGLT2 (gliflozines) : d'EMPA-REG OUTCOME a CANVAS.
Scheen, André ULiege; Ernest, Philippe; Jandrain, Bernard

in Revue Médicale Suisse (2017), 13(571), 1421-1426

The cardiovascular (CV) and renal protection reported with empagliflozin in EMPA-REG OUTCOME is now confirmed with canagliflozin in CANVAS in patients with type 2 diabetes and high cardiovascular risk ... [more ▼]

The cardiovascular (CV) and renal protection reported with empagliflozin in EMPA-REG OUTCOME is now confirmed with canagliflozin in CANVAS in patients with type 2 diabetes and high cardiovascular risk: similar and significant reductions in major CV events (-14 vs. -14%), in hospitalisations for heart failure (-35 vs. -33%) and in renal events (-39 vs. -40%). The greater reduction in CV mortality (-38 vs. - 13%) and all-cause mortality (-32 vs. -13%) in EMPA-REG OUTCOME than in CANVAS may be explained by the greater proportion of patients with CV disease (secondary prevention : 99 vs. 65%). In contrast to EMPA-REG OUTCOME, CANVAS did not show an increase in stroke (-10%, NS), but reported a higher rate of fractures and amputations with canagliflozin. Overall, these results support a class effect for the cardiorenal protection by inhibitors of sodium-glucose type 2 (SGLT2) cotransporters. [less ▲]

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See detailEditorial - De la notion de <<bonne sante>> a des cas pathologiques exemplatifs.
Scheen, André ULiege

in Revue Médicale de Liège (2017), 72(7-8), 325-326

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See detailCanagliflozin: A Review in Type 2 Diabetes.
Deeks, Emma D.; Scheen, André ULiege

in Drugs (2017)

Canagliflozin (Invokana(R)) is a sodium-glucose co-transporter-2 (SGLT2) inhibitor indicated in various countries worldwide for the once-daily oral treatment of type 2 diabetes (T2D). Canagliflozin lowers ... [more ▼]

Canagliflozin (Invokana(R)) is a sodium-glucose co-transporter-2 (SGLT2) inhibitor indicated in various countries worldwide for the once-daily oral treatment of type 2 diabetes (T2D). Canagliflozin lowers blood glucose levels independently of insulin, with the inhibition of SGLT2 reducing renal reabsorption of glucose and increasing excretion of glucose in the urine. In well-designed clinical trials, canagliflozin (as first-line monotherapy or add-on therapy to other antihyperglycaemic agents) improved glycaemic control in adults with T2D, including those of older age and/or at high cardiovascular (CV) risk, and also had beneficial effects on their bodyweight and blood pressure (BP). CV risk reduction, as well as possible renal benefits, were also seen with canagliflozin in T2D patients at high CV risk in the CANVAS Program, an integrated analysis of two large CV outcomes studies. Canagliflozin was generally well tolerated, had a low risk of hypoglycaemia and was most commonly associated with adverse events such as genital and urinary tract infections and increased urination, consistent with its mechanism of action. Although the amputation and fracture risk observed among recipients of the drug require further investigation, canagliflozin is an important option for T2D management in adults. [less ▲]

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See detailInhibiteur de la DPP-4 ou des SGLT2 apres echec de la metformine seule dans le diabete de type 2.
Paquot, Nicolas ULiege; Scheen, André ULiege

in Revue Médicale Suisse (2017), 13(571), 1410-1415

After failure of a monotherapy with metformin, dipeptidyl peptidase-4 inhibitors (gliptins) and sodium-glucose cotransporters type 2 (gliflozins) offer an alternative to the add-on of a sulphonylurea ... [more ▼]

After failure of a monotherapy with metformin, dipeptidyl peptidase-4 inhibitors (gliptins) and sodium-glucose cotransporters type 2 (gliflozins) offer an alternative to the add-on of a sulphonylurea, especially in diabetic patients at risk of hypoglycaemia. The choice between a gliptin and a gliflozin may be guided by the individual patient characteristics : rather a gliptin in a patient without obesity or severe hyperglycaemia, in an elderly patient, with a frailty profile or with renal impairment; rather a gliflozin in an obese patient, with hypertension, hyperuricaemia, antecedents of cardiovascular disease (especially heart failure), without advanced renal insufficiency and with a low risk of urinary/genital infections or events linked to dehydration such as hypotension. [less ▲]

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See detailOptions therapeutiques chez un patient diabetique de type 2 mal controle par une insuline basale.
Scheen, André ULiege; Paquot, Nicolas ULiege

in Revue Médicale Suisse (2017), 13(571), 1416-1420

In a patient with type 2 diabetes not well controlled with a basal insulin - metformin combination, several therapeutic options may be considered: intensifying insulin therapy with different schemes ... [more ▼]

In a patient with type 2 diabetes not well controlled with a basal insulin - metformin combination, several therapeutic options may be considered: intensifying insulin therapy with different schemes (appropriate titration using a more favourable basal insulin analogue, adding one, two or three rapid-acting insulin analogues, shift to two or three premix insulin injections), adding a dipeptidyl peptidase-4 inhibitor (gliptin) or an inhibitor of sodium-glucose cotransporters type 2 (gliflozin), or combining a glucagon-like peptide-1 receptor agonist with basal insulin. The choice should be made according the individual profile and preference of the patient, in a personalized approach, taking into account the advantages and disadvantages of each therapeutic solution. [less ▲]

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See detailPossible survivorship bias rather than reverse causality in EMPA-REG OUTCOME.
Scheen, André ULiege

in Diabetes Research & Clinical Practice (2017), (May),

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See detailSemaglutide: a promising new glucagon-like peptide-1 receptor agonist.
Scheen, André ULiege

in Lancet Diabetes & Endocrinology (2017)

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See detailGLP-1 receptor agonists and heart failure in diabetes.
Scheen, André ULiege

in Diabètes & Métabolism (2017), 43 Suppl 1

The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization ... [more ▼]

The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization. Such an increased risk has been consistently reported with thiazolidinediones (glitazones) and perhaps also with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR - TIMI 53), whereas a markedly decreased risk was highlighted with the sodium - glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME. Yet, the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on myocardial function remain controversial. Whereas some promising observations have been reported in various animal models, the effects of GLP-1RAs on myocardial function in humans are more heterogeneous, while the positive effect on left ventricular ejection fraction (LVEF), if any, appears to be inconsistent and rather modest in most patients with HF. However, no increased risk of hospitalization for HF has been reported with GLP-1RAs in meta-analyses of phase-II/III trials (exenatide, albiglutide, dulaglutide, liraglutide), demonstrating the safety of this pharmacological class, and such findings have been confirmed by three large prospective cardiovascular outcome trials (ELIXA with lixisenatide, LEADER with liraglutide and SUSTAIN-6 with semaglutide). In particular, LEADER reported a trend towards a reduction in HF hospitalization (-13%, P = 0.14), together with a significant reduction in cardiovascular and all-cause mortality in patients with T2D at risk of cardiovascular disease. These results are reassuring in the face of the somewhat negative results of the FIGHT trial, which evaluated the effects of liraglutide in patients with advanced HF and low LVEF, such that further studies and caution are now required when using this agent to treat such patients in clinical practice. [less ▲]

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See detailCardiovascular outcome studies with incretin-based therapies: Comparison between DPP-4 inhibitors and GLP-1 receptor agonists.
Scheen, André ULiege

in Diabetes Research & Clinical Practice (2017), 127

Dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent two distinct classes of incretin-based therapies used for the treatment of type 2 diabetes ... [more ▼]

Dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent two distinct classes of incretin-based therapies used for the treatment of type 2 diabetes. Non-inferiority versus placebo was shown in large prospective cardiovascular outcome trials in patients with high cardiovascular risk: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin); ELIXA (lixisenatide), LEADER (liraglutide) and SUSTAIN 6 (semaglutide). The promises raised by meta-analyses of phase 2-3 trials with DPP-4is were non confirmed as no cardiovascular protection could be evidenced. However, LEADER showed a significant reduction in major cardiovascular events, myocardial infarction, cardiovascular and all-cause mortality in patients treated by liraglutide compared to placebo. These positive results contrasted with the non-inferiority results with lixisenatide in ELIXA. They were partially confirmed with semaglutide in SUSTAIN 6 despite the absence of reduction in cardiovascular mortality. Hospitalisation for heart failure was not increased except with saxagliptin in SAVOR-TIMI 53. The reasons for different outcomes between trials remain largely unknown as well as the precise underlying mechanisms explaining the cardiovascular protection by liraglutide. The clinical relevance of results with DPP-4is and GLP-1RAs is discussed. Ongoing trials with linagliptin and several once-weekly GLP-1RAs should provide new insights into remaining fundamental questions. [less ▲]

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See detailVignette therapeutique de l'etudiant. Optimisation d'un traitement par insuline basale chez le patient diabetique de type 2.
Scheen, André ULiege; Paquot, Nicolas ULiege

in Revue Médicale de Liège (2017), 72(3), 156-161

Because of the natural history of type 2 diabetes and the increasing life expectancy, more and more patients are treated with insulin after failure of oral therapy. International guidelines give the ... [more ▼]

Because of the natural history of type 2 diabetes and the increasing life expectancy, more and more patients are treated with insulin after failure of oral therapy. International guidelines give the preference to basal insulin, most often while maintaining metformin. If this treatment does not allow to reach the glycaemic objectives, optimizing therapy is mandatory. This clinical case offers the opportunity of discussing both advantages and disadvantages of three therapeutic options : the shift from basal insulin to a basal-plus or a basal-bolus insulin regimen, the addition of another oral glucose-lowering agent, either a dipeptidyl peptidase-4 inhibitor (gliptin) or an inhibitor of cotransporters sodium-glucose type 2 cotransporters (gliflozin), or the combination of basal insulin and a glucagon-like peptide-1 receptor agonist. [less ▲]

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