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See detailType 2 diabetes mellitus and osteoarthritis
Veronese, Nicola; Cooper, Cyrus; Reginster, Jean-Yves ULiege et al

in Seminars in Arthritis and Rheumatism (in press)

OBJECTIVES: Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are common diseases that frequently co-exist, along with overweight/obesity. While the mechanical impact of excess body weight on joints ... [more ▼]

OBJECTIVES: Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are common diseases that frequently co-exist, along with overweight/obesity. While the mechanical impact of excess body weight on joints may explain lower limb OA, we sought to explore whether T2DM is linked to OA outside of excess weight and whether T2DM may play a role in OA pathophysiology. The consequence of T2DM on OA outcomes is a question of research interest. METHODS: We conducted a critical review of the literature to explore the association between T2DM and OA, whether any association is site-specific for OA, and whether the presence of T2DM impacts on OA outcomes. We also reviewed the literature to assess the safety of anti-OA treatments in patients with T2DM. RESULTS: T2DM has a pathogenic effect on OA through 2 major pathways involving oxidative stress and low-grade chronic inflammation resulting from chronic hyperglycemia and insulin resistance. T2DM is a risk factor for OA progression and has a negative impact on arthroplasty outcomes. Evidence is mounting for safety concerns with some of the most frequently prescribed anti-OA medications, including paracetamol, non-steroidal anti-inflammatory drugs, and corticosteroid injections, while other anti-OA medications may be safely prescribed in OA patients with T2DM, such as glucosamine and intra-articular hyaluronic acid. CONCLUSIONS: Future research is needed to better understand whether diabetes control and prevention can modulate OA occurrence and progression. The selection of therapy to treat OA symptoms in patients with T2DM may require careful consideration of the evidence based to avoid untoward safety issues. [less ▲]

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See detailPrise de position de la Société Francophone du Diabète (SFD) sur la prise en charge médicamenteuse de l'hyperglycémie du patient diabétique de type 2
Bauduceau, Bernard; Bordier, Lyse; Bringer, Jacques et al

in Médecine des Maladies Métaboliques (2019), 13(2), 577-593

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See detailIntérêt des inhibiteurs SGLT-2 dans le diabète de type 1
PHILIPS, Jean-Christophe ULiege; PAQUOT, Nicolas ULiege; SCHEEN, André ULiege

in Diabetes and Metabolism (2019)

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See detailÉtudes cardiovasculaires chez le patient diabétique de type 2 à risque : conclusions et impact des essais publiés en 2017-2018
SCHEEN, André ULiege

in Médecine des Maladies Métaboliques (2019), 13(supplément 1), 10-24

Les études à visée cardiovasculaire (CV) dans le diabète de type 2 (DT2) ont concerné les trois classes antidiabétiques les plus récentes, les inhibiteurs de la dipeptidyl peptidase-4 (DPP-4) (gliptines ... [more ▼]

Les études à visée cardiovasculaire (CV) dans le diabète de type 2 (DT2) ont concerné les trois classes antidiabétiques les plus récentes, les inhibiteurs de la dipeptidyl peptidase-4 (DPP-4) (gliptines), les agonistes des récepteurs du glucagon-like peptide-1 (GLP-1), et les inhibiteurs des cotransporteurs sodium-glucose de type 2 (SGLT2) (gliflozines). Les gliptines ont démontré leur sécurité cardiovasculaire, mais sans supériorité par rapport à un placebo. Les agonistes des récepteurs du GLP-1 ont montré une protection CV chez des patients à haut risque CV, mais avec certains résultats discordants selon les molécules testées. Les gliflozines ont montré une réduction des événements CV majeurs, tout en réduisant les hospitalisations pour insuffisance cardiaque et les événements rénaux. Les résultats des essais initiaux ont été généralement confirmés dans des études récentes, respectivement CARMELINA pour les gliptines, EXSCEL et HARMONY OUTCOMES pour les agonistes des récepteurs du GLP-1, et CANVAS et DECLARE-TIMI 58 pour les inhibiteurs des SGLT2. Les résultats de ces essais cliniques contrôlés ont considérablement impacté la nouvelle stratégie de prise en charge de l’hyperglycémie chez les patients DT2 dans le consensus ADA-EASD 2018. D’autres essais sont en cours, en particulier avec les inhibiteurs des SGLT2 chez des patients avec insuffisance cardiaque ou atteinte rénale. [less ▲]

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See detailBeneficial effects of SGLT2 inhibitors on fatty liver in type 2 diabetes: A common comorbidity associated with severe complications.
Scheen, André ULiege

in Diabetes & metabolism (2019)

Patients with type 2 diabetes mellitus (T2DM) are exposed to non-alcoholic fatty liver disease (NAFLD), a comorbidity associated with cardiovascular disease and chronic kidney disease, and which may ... [more ▼]

Patients with type 2 diabetes mellitus (T2DM) are exposed to non-alcoholic fatty liver disease (NAFLD), a comorbidity associated with cardiovascular disease and chronic kidney disease, and which may progress to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Sodium-glucose cotransporter type-2 (SGLT2) inhibitors are glucose-lowering agents that improve glucose control while promoting weight loss and lowering serum uric acid levels. These agents may exert cardiovascular and renal protection in T2DM patients with established cardiovascular disease. Recent findings from both randomized controlled trials and open-label studies have also shown that SGLT2 inhibitors are able to reduce fatty liver content, as assessed by different imaging techniques, and improve biological markers of NAFLD, especially serum liver enzymes, in patients with T2DM. In addition, there are emerging data to suggest a mechanism beyond the reduction of hyperglycaemia and body weight, and a potential role for the decrease in low-grade inflammation and oxidative stress associated with SGLT2 inhibitor therapy. This positive effect of SGLT2 inhibitors on NAFLD complements their already well-known effects on cardiovascular and chronic kidney diseases. [less ▲]

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See detailAn update on the safety of SGLT2 inhibitors.
Scheen, André ULiege

in Expert opinion on drug safety (2019), 18(4), 295-311

INTRODUCTION: Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) are recommended after metformin for a large spectrum of patients with type 2 diabetes, because of a favorable benefit/risk profile ... [more ▼]

INTRODUCTION: Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) are recommended after metformin for a large spectrum of patients with type 2 diabetes, because of a favorable benefit/risk profile despite a variety of adverse events. Areas covered: This narrative review discusses the safety profile of SGLT2is: initial concerns (cardiovascular safety, acute renal failure, hypoglycemia, urinary and genital infections, volume depletion, bladder cancer), further concerns (euglycemic ketoacidosis, bone fractures) and more recent concerns (lower limb amputation, Fournier's gangrene). Expert opinion: Overall, the safety profile of SGLT2is is good. The only increased adverse event that was consistently reported in clinical trials and observational studies is genital mycotic infections, with only a borderline increase in urinary tract infections. Among clinical trials, only the CANVAS program reported an unexpected increase in bone fractures and peripheral amputations. A variety of rare adverse events have been described as case reports, including ketoacidosis, amputations and Fournier gangrene, which led to specific warnings by regulatory agencies. Identifying predisposing patient's characteristics and/or precipitating clinical conditions would help prevent the most severe complications. These adverse events should not mask the overall cardiovascular and renal benefit of SGLT2is, especially in patients with type 2 diabetes at high cardiovascular risk. [less ▲]

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See detailFocus sur l'empagliflozine. Synthese des analyses post hoc de l'etude cardiovasculaire empa-reg outcome.
Scheen, André ULiege

in Revue medicale de Liege (2019), 74(4), 185-191

EMPA-REG OUTCOME trial studied the cardiovascular safety of empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, compared to placebo, in patients with type 2 diabetes and high ... [more ▼]

EMPA-REG OUTCOME trial studied the cardiovascular safety of empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, compared to placebo, in patients with type 2 diabetes and high cardiovascular risk. It showed a significant reduction of major cardiovascular events (-14 %), cardiovascular mortality (-38 %), all-cause death (-32 %), hospitalisations for heart failure (-35 %) and progression of renal disease (-39 %). This article proposes an update, almost 4 years after the original publication, of recent post hoc analyses of this landmark study. [less ▲]

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See detailLe medicament du mois. Insuline basale degludec (Tresiba(R)).
Scheen, André ULiege; Mathieu, Chantal

in Revue medicale de Liege (2019), 74(4), 226-232

Insulin degludec (Tresiba(R)) is characterized by an original mode of prolonged and continuous insulin release after its subcutaneous injection. Thereby, it has a very long glucose-lowering effect, around ... [more ▼]

Insulin degludec (Tresiba(R)) is characterized by an original mode of prolonged and continuous insulin release after its subcutaneous injection. Thereby, it has a very long glucose-lowering effect, around 42 hours, and a better reproducibility from both a pharmacokinetic and pharmacodynamic point of view. Its efficacy and safety have been assessed in the phase 3 clinical programme BEGIN as compared with insulin glargine U100, in patients with type 1 diabetes (T1D) and type 2 (T2D). For a similar glucose control (reduction in glycated haemoglobin), less hypoglycaemic episodes were recorded, including severe hypoglycaemia, during the nocturnal period, with insulin degludec than with insulin glargine U100. This clinical benefit has been confirmed in the complementary SWITCH programme in T1D and T2D patients at higher risk of hypoglycaemia, in the double-blind cardiovascular outcome trial DEVOTE in T2D patients at high cardiovascular risk and in real-life conditions in the observational European EU-TREAT study in patients with T1D and T2D. Insulin degludec (Tresiba(R)) is indicated and reimbursed for the treatment of patients with T1D, combined with a prandial insulin, and T2D, alone or combined with oral antidiabetic agents, a glucagon-like peptide-1 receptor agonist or a short-acting insulin. [less ▲]

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See detailLe medicament du mois. Combinaison a ratio fixe insuline basale glargine-lixisenatide (Suliqua(R)).
Scheen, André ULiege

in Revue Médicale de Liège (2019), 74(2), 111-116

Suliqua(R) (iGlarLixi) is a fixed ratio combination of basal insulin glargine U100 and the glucagon-like peptide-1 (GLP-1) receptor agonist lixisenatide. Both molecules exert complementary ... [more ▼]

Suliqua(R) (iGlarLixi) is a fixed ratio combination of basal insulin glargine U100 and the glucagon-like peptide-1 (GLP-1) receptor agonist lixisenatide. Both molecules exert complementary antihyperglycaemic effects : insulin glargine mainly targets fasting glycaemia while lixisenatide mainly targets postprandial hyperglycaemia. Thus, iGlarLixi is associated with a greater reduction in glycated haemoglobin (HbA1c) than each individual component and thereby results in a greater percentage of patients reaching HbA1c ? 7 %. It has a good tolerance profile, with a more favourable effect on body weight compared with insulin glargine alone and less gastrointestinal adverse effects when compared with lixisenatide alone, because of a more progressive titration of the GLP-1 receptor agonist component. iGlarLixi (Suliqua(R)) is presented as two different prefilled pens, one allowing to titrate glargine up to 40 IU/day, the other up to 60 IU/day, both with lixisenatide uptitrated to a maximum of 20 microg/day. This dual presentation facilitates a personalized approach according to patient's needs. Suliqua(R) is currently reimbursed, under conditions, for the management of type 2 diabetes not well controlled with basal insulin associated or not with oral antidiabetic agents. [less ▲]

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See detailPreventing and treating kidney disease in patients with type 2 diabetes
DELANAYE, Pierre ULiege; SCHEEN, André ULiege

in Expert Opinion on Pharmacotherapy (2019), 20(3), 277-294

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See detailComplications metaboliques et carences nutritionnelles liees a une consommation excessive d'alcool.
De Flines, J.; Scheen, André ULiege; Paquot, Nicolas ULiege

in Revue medicale de Liege (2019), 74(5-6), 304-309

Metabolic disturbances associated with chronic alcohol consumption, among which those affecting glucose regulation, lipid profile, uric acid and nutritional status, are described. In fact, alcohol abuse ... [more ▼]

Metabolic disturbances associated with chronic alcohol consumption, among which those affecting glucose regulation, lipid profile, uric acid and nutritional status, are described. In fact, alcohol abuse can lead to overweight and obesity, but also to protein-caloric malnutrition. Finally, we will discuss concerns about vitamin and mineral deficiencies that may be observed in alcoholic people and can contribute to aggravate somatic complications. [less ▲]

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See detailL'alcool, facteur protecteur ou facteur de risque pour les maladies cardiovasculaires ?
Scheen, André ULiege

in Revue medicale de Liege (2019), 74(5-6), 314-320

Alcohol may exert both positive and negative effects on cardiovascular system. Several factors may modulate these effects, among which, most importantly, the daily dose but also consumption modalities ... [more ▼]

Alcohol may exert both positive and negative effects on cardiovascular system. Several factors may modulate these effects, among which, most importantly, the daily dose but also consumption modalities (type of beverage, regular or hectic consumption, for instance). Many epidemiological studies showed a J curve, with a greater risk of cardiovascular disease in non-consumers compared with light to moderate regular drinkers, but with a higher risk in heavy drinkers, in a dose-dependent manner. This article analyses the complex relationships between alcohol consumption and the risk of coronary and cerebrovascular diseases, including cardiovascular mortality. Owing to the remaining uncertainties, in absence of controlled trials, and the difficulty not to overcome the positive threshold, it is not currently recommended to drink alcohol in order to benefit of a cardiovascular protection. [less ▲]

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See detailAlcool et conduite automobile.
Scheen, André ULiege

in Revue medicale de Liege (2019), 74(5-6), 258-264

Alcohol intoxication during car driving represents a well-recognized danger and is responsible for numerous accidents leading to premature death or infirmities. The objectives of this article are to ... [more ▼]

Alcohol intoxication during car driving represents a well-recognized danger and is responsible for numerous accidents leading to premature death or infirmities. The objectives of this article are to describe some epidemiological data about driving under alcohol influence and associated car accidents, to remind which alcohol blood concentrations are acceptable from a legal point of view, to analyse the acute effects of alcohol on cortical function that could alter driving capacities and, finally, to consider some conditions that may reduce or increase the effects of alcohol on the performances during car driving. Keywords : Alcohol - Car accident - Driving - Brain. [less ▲]

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See detailEditorial. L'alcool, probleme de sante publique : de la consommation hedonique a la decheance physique et psychologique.
Scheen, André ULiege

in Revue medicale de Liege (2019), 74(5-6), 237-240

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See detailInhibiteurs des SGLT2 et « perte de chance » : une interprétation diamétralement opposée de la Commission de Transparence de la Haute Autorité de santé (HAS) et de la Société Francophone du Diabète (SFD)
SCHEEN, André ULiege

in Médecine des Maladies Métaboliques (2019), 13(3), 309-312

The « loss of chance » is a legal term whose definition is a prejudice characterized by the deprivation of a probable gain or the occurrence of a loss that could have been avoided. This notion has been ... [more ▼]

The « loss of chance » is a legal term whose definition is a prejudice characterized by the deprivation of a probable gain or the occurrence of a loss that could have been avoided. This notion has been expanded to medical practice. As far the evaluation of sodium-glucose type 2 cotransporter inhibitors (SGLT2i, or gliflozins), the Société Francophone du Diabète (SFD) has a completely different view about the interpretation of the loss of chance given by the Commission de Transparence of the French Haute Autorité de santé (HAS). For the latter, the loss of chance associated with the prescription of a SGLT2i would correspond to a loss, i.e. the risk of severe adverse events, which may be avoided if another already available antidiabetic agent would have been prescribed instead of a SGLT2i. In contrast, for the SFD, the loss of chance results in the privation of a potential gain, i.e. a well demonstrated cardiovascular and renal protection, at least in patients with type 2 diabetes and at high risk. [less ▲]

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See detailDiabetes Research & Clinical Practice Series : Implications of the recent CVOTs in Type 2 Diabetes: Impact on guidelines: the endocrinologist point of view.
Scheen, André ULiege

in Diabetes research and clinical practice (2019)

The management of type 2 diabetes mellitus (T2DM) essentially consists in controlling hyperglycaemia, together with other vascular risk factors, in order to reduce the incidence and severity of diabetic ... [more ▼]

The management of type 2 diabetes mellitus (T2DM) essentially consists in controlling hyperglycaemia, together with other vascular risk factors, in order to reduce the incidence and severity of diabetic complications. Whereas glucose control using classical glucose-lowering agents (except perhaps metformin) largely fails to reduce cardiovascular disease (CVD), two new pharmacological classes, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter type 2 inhibitors (SGLT2is), have proven their ability to reduce major cardiovascular events in patients with established CVD. Furthermore, SGLT2is reduced the risk of hospitalisation for heart failure and the progression of renal disease. According to the 2018 ADA-EASD consensus report, the choice of a second agent to be added to metformin should now be driven by the presence or not of atherosclerotic CVD, heart failure or renal disease, all conditions that should promote the use of a SGLT2i or a GLP-1 RA with proven efficacy. Thus endocrinologists have to face a new paradigm in the management of T2DM, with a shift from a primary objective of glucose control without inducing hypoglycaemia and weight gain to a goal of cardiovascular and renal protection, largely independent of glucose control. Of note, however, the latter remains crucial to reduce the risk of microangiopathy. [less ▲]

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See detailAssessment of the benefit-risk balance of SGLT2 inhibitors: Commentary on a new 'French paradox'.
Scheen, André ULiege; Darmon, P.; Hanaire, H.

in Diabetes & metabolism (2019)

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See detailIncreased risk of severe hypoglycemic events before and after cardiovascular outcomes in TECOSSuggests an at-risk type 2 diabetes frail patient phenotype
Standl, E.; Stevens, S. R.; Armstrong, P. W. et al

in Diabetes Care (2018), 41(3), 596-603

OBJECTIVE Severe hypoglycemic events (SHEs) in type 2 diabetes are associated with subsequent cardiovascular (CV) event risk.We examined whether CV events were associated with subsequent SHE risk ... [more ▼]

OBJECTIVE Severe hypoglycemic events (SHEs) in type 2 diabetes are associated with subsequent cardiovascular (CV) event risk.We examined whether CV events were associated with subsequent SHE risk. RESEARCH DESIGN AND METHODS Time-dependent associations between SHEs and a composite CV end point (fatal/ nonfatal myocardial infarction or stroke, hospitalization for unstable angina, hospitalization for heart failure [hHF]) were examined post hoc in 14,671 TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) participants with type 2 diabetes and CV disease followed for a median of 3.0 years. RESULTS SHEs were uncommon and unassociated with sitagliptin therapy (N = 160 [2.2%], 0.78/100 patient-years vs. N = 143 [1.9%], 0.70/100 patient-years for placebo; hazard ratio [HR] 1.12 [95%CI 0.89, 1.40], P = 0.33). Patientswith (versus without) SHEswere older with longer diabetes duration, lower body weight, and lower estimated glomerular filtration rate;weremore frequentlywomen, nonwhite, and insulin treated; and more often had microalbuminuria or macroalbuminuria. Analyses adjusted for clinical factors showed SHEs were associated with increased risk of the primary composite CV end point (1.55 [1.06, 2.28], P = 0.025), all-cause death (1.83 [1.22, 2.75], P = 0.004), and CV death (1.72 [1.02, 2.87], P = 0.040). Conversely, nonfatal myocardial infarction (3.02 [1.83, 4.96], P < 0.001), nonfatal stroke (2.77 [1.36, 5.63], P = 0.005), and hHF (3.68 [2.13, 6.36], P < 0.001) were associated with increased risk of SHEs. Fully adjusted models showed no association between SHEs and subsequent CV or hHF events, but the association between CV events and subsequent SHEs remained robust. CONCLUSIONS These findings, showing greater risk of SHEs after CV events and greater risk of CV events after SHEs, suggest a common at-risk type 2 diabetes frail patient phenotype. © 2017 by The American Diabetes Association. [less ▲]

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See detailPrise en charge de l'hyperglycemie du diabete de type 2 Changement de paradigme selon le consensus ADA-EASD 2018.
Scheen, André ULiege; Paquot, Nicolas ULiege

in Revue medicale de Liege (2018), 73(12), 629-633

The strategy for the management of hyperglycaemia in type 2 diabetes was updated in October 2018 by a group of experts of the American Diabetes Association (ADA) and the European Association for the Study ... [more ▼]

The strategy for the management of hyperglycaemia in type 2 diabetes was updated in October 2018 by a group of experts of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). They are triggered by the results of cardiovascular outcome trials published since 2015, which demonstrated a cardiovascular (and renal) protection with two classes of medications, SGLT2 inhibitors (gliflozins) and some GLP-1 receptor agonists (mainly liraglutide) in patients with established cardiovascular disease. Thus, after failure of lifestyle and metformin, the addition of one of these agents is recommended in presence of atherosclerotic cardiovascular disease. In case of heart failure or renal disease, the preference is given to a SGLT2 inhibitor, provided that estimated glomerular filtration rate is adequate (superior to 45-60 ml/min/1.73 m(2)). In all other patients, the choice is guided by the main objective, in concertation with the patient : to reduce the risk of hypoglycaemia (gliptin, gliflozin, pioglitazone or GLP1 receptor agonist), body weight excess (SGLT2 inhibitor or GLP-1 receptor) or medication cost (sulphonylurea, pioglitazone). If oral treatment is insufficient, the preference is now given to a GLP-1 receptor agonist rather than basal insulin. Thus, instead of a glucocentric and metabolic viewpoint predominant in the previous position statement, a paradigm change is proposed, focusing on cardiovascular and renal protection, within a patient-centred approach. [less ▲]

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