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 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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See detailPharmacokinetic drug evaluation of saxagliptin plus dapagliflozin for the treatment of type 2 diabetes.
Scheen, André ULiege

in Expert Opinion on Drug Metabolism & Toxicology (2017), 13(5), 583-592

INTRODUCTION: Combining a dipeptidyl peptidase-4 inhibitor and a sodium-glucose cotransporter type 2 inhibitor is an attractive option to treat hyperglycaemia in type 2 diabetes. Areas covered: The ... [more ▼]

INTRODUCTION: Combining a dipeptidyl peptidase-4 inhibitor and a sodium-glucose cotransporter type 2 inhibitor is an attractive option to treat hyperglycaemia in type 2 diabetes. Areas covered: The saxagliptin plus dapagliflozin combination is carefully analysed, focusing on: 1) pharmacokinetic properties, 2) pharmacodynamics data, and 3) results of randomised controlled trials (dual combination versus either monotherapy, sequential therapy saxagliptin added to dapagliflozin or dapagliflozin added to saxagliptin). Expert opinion: Pharmacokinetic findings demonstrate the absence of drug-drug interaction and the bioequivalence of the FDC compared with separated tablets. Pharmacodynamic observations confirm a complementary mode of action of the two agents. Dual saxagliptin-dapagliflozin therapy is more potent than either monotherapy. It may be used as an initial combination, although this approach remains debatable and should probably be reserved in case of high glycated hemoglobin, or a stepwise strategy, according to a personalized approach. The developed saxagliptin-dapagliflozin FDC may simplify anti-hyperglycemic therapy and improve drug compliance. [less ▲]

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See detailFactors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.
Scheen, André ULiege; Schmitt, H.; Jiang, H. H. et al

in Diabètes & Métabolism (2017), 43(69-78),

AIMS: To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA1c) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as ... [more ▼]

AIMS: To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA1c) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. METHODS: This post-hoc analysis of insulin-naive patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA1c of <7.0% (<53mmol/mol) per baseline HbA1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia. RESULTS: Patients had comparable demographic characteristics and similar HbA1c and FHG values at baseline in each HbA1c quartile regardless of whether they reached the target HbA1c. The higher the HbA1c quartile, the greater was the decrease in HbA1c, but also the smaller the percentage of patients achieving the target HbA1c. HbA1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA1c quartiles with either insulin treatment. Patients not achieving the target HbA1c had slightly higher insulin doses, but lower total hypoglycaemia rates. CONCLUSION: Smaller decreases in FHG were associated with not reaching the target HbA1c, suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens. [less ▲]

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See detailEffects of reducing blood pressure on renal outcomes in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME.
Scheen, André ULiege; Delanaye, P.

in Diabètes & Métabolism (2017), (epub ahead of print),

Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has enabled remarkable reductions in cardiovascular and all-cause mortality as well as in renal outcomes in patients with type 2 ... [more ▼]

Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has enabled remarkable reductions in cardiovascular and all-cause mortality as well as in renal outcomes in patients with type 2 diabetes (T2D) and a history of cardiovascular disease in the EMPA-REG OUTCOME. These results have been attributed to haemodynamic rather than metabolic effects, in part due to the osmotic/diuretic action of empagliflozin and the reduction in arterial blood pressure (BP). The present narrative review includes the results of meta-analyses of trials evaluating the effects on renal outcomes of lowering BP in patients with T2D, with a special focus on the influence of baseline and achieved systolic BP, and compares the renal outcome results of the EMPA-REG OUTCOME with those of other major trials with inhibitors of the renin-angiotensin system in patients with T2D and the preliminary findings with other SGLT2 inhibitors, and also evaluates post hoc analyses from the EMPA-REG OUTCOME of special interest as regards the BP-lowering hypothesis and renal function. While systemic BP reduction associated to empagliflozin therapy may have contributed to the renal benefits reported in EMPA-REG OUTCOME, other local mechanisms related to kidney homoeostasis most probably also played a role in the overall protection observed in the trial. [less ▲]

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See detailPharmacotherapy of 'treatment resistant' type 2 diabetes.
Scheen, André ULiege

in Expert Opinion on Pharmacotherapy (2017), 1

INTRODUCTION: Despite type 2 diabetes (T2D) management offers a variety of pharmacological interventions targeting different defects, numerous patients remain with persistent hyperglycaemia responsible ... [more ▼]

INTRODUCTION: Despite type 2 diabetes (T2D) management offers a variety of pharmacological interventions targeting different defects, numerous patients remain with persistent hyperglycaemia responsible for severe complications. Unlike resistant hypertension, treatment resistant T2D is not a classical concept although it is a rather common observation in clinical practice. Areas covered: This article proposes a definition for 'treatment resistant diabetes', analyses the causes of poor glucose control despite standard therapy, briefly considers the alternative approaches to glucose-lowering pharmacotherapy and finally describes how to overcome poor glycaemic control, using innovative oral or injectable combination therapies. Expert opinion: Before considering intensifying the pharmacotherapy of a patient with poorly controlled T2D, it is important to verify treatment adherence, target obesity and consider various non pharmacological improvement quality interventions. If treatment resistant diabetes is defined as not achieving glycated haemoglobin target despite oral triple therapy with a third glucose-lowering agent added to metformin-sulfonylurea dual treatment, the combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor and a sodium glucose cotransporter type 2 (SGLT2) inhibitor may offer new opportunities before considering injectable therapies. Insulin basal therapy (+/- metformin) may be optimized by the addition of a SGLT2 inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist. [less ▲]

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See detailDulaglutide for the treatment of type 2 diabetes.
Scheen, André ULiege

in Expert Opinion on Biological Therapy (2017), 17(4), 485-496

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are injectable agents used for the treatment of hyperglycemia in type 2 diabetes. The interest for this pharmacological class is rising ... [more ▼]

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are injectable agents used for the treatment of hyperglycemia in type 2 diabetes. The interest for this pharmacological class is rising with the development of once weekly compounds and the demonstration of a potential reduction in cardiorenal outcomes. Areas covered: The paper describes the main pharmacokinetic/pharmacodynamic characteristics of dulaglutide, a new once-weekly GLP-1 RA. Dulaglutide was extensively investigated in the phase-3 AWARD program, which demonstrated its safety and efficacy when compared to placebo or active glucose-lowering agents in patients treated with diet alone, metformin or sulfonylurea monotherapy, oral dual therapies and basal insulin. In both Caucasian and Japanese patients, comparative trials showed better glucose control with dulaglutide, with a minimal risk of hypoglycemia and weight loss, but at the expense of an increased dropout rate due to side effects, mostly transient gastrointestinal disturbances. Dulaglutide proved its non-inferiority versus liraglutide and the safety and tolerance profile is similar to that of other GLP-1 RAs. Expert opinion: The once-weekly formulation and the combined positive effects on both glucose control and weight improves patient satisfaction despite nausea. Dulaglutide must prove its capacity to reduce cardiovascular and diabetic complications in the ongoing prospective REWIND trial. [less ▲]

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See detailUnderstanding and overcoming metformin gastrointestinal intolerance.
Bonnet, Fabrice; Scheen, André ULiege

in Diabetes, Obesity & Metabolism (2017), 19(473-481),

Metformin is the most widely prescribed drug for patients with type 2 diabetes mellitus and the first-line pharmacologic option as supported by multiple international guidelines, yet a rather large ... [more ▼]

Metformin is the most widely prescribed drug for patients with type 2 diabetes mellitus and the first-line pharmacologic option as supported by multiple international guidelines, yet a rather large proportion of patients cannot tolerate metformin in adequate amounts because of its associated gastrointestinal (GI) adverse events (AEs). GI AEs typically encountered with metformin therapy include diarrhoea, nausea, flatulence, indigestion, vomiting, and abdominal discomfort, with diarrhoea and nausea being the most common. Although starting at a low dose and titrating slowly may help prevent some of metformin's GI AEs, some patients are unable to tolerate metformin at all and it may also be difficult to convince patients to start metformin again after a bout of GI AEs. Despite this clinical importance the underlying mechanisms of metformin's GI intolerance are poorly known. This review discusses the epidemiology of metformin GI intolerance; its underlying mechanisms; genotype variability and associated factors affecting metformin GI intolerance, such as comorbidities, co-medications, and bariatric surgery; clinical consequences, and therapeutic strategies to overcome metformin GI intolerance. These strategies include appropriate titration of immediate-release metformin, use of extended-release metformin, the promise of delayed-release metformin and gut microbiome modulators, and alternative pharmacological therapies when metformin cannot be tolerated at all. Given the available data, all efforts should be made to maintain metformin before considering a shift to another drug therapy. [less ▲]

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