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See detailLa vignette thérapeutique de l'étudiant. Le choix entre un inhibiteur de la DPP-4 et un inhibiteur des SGLT2 pour traiter le diabète de type 2 (2016)
SCHEEN, André ULg; PAQUOT, Nicolas ULg

in Revue Médicale de Liège (2016), 71(12), 579-585

Summary : Two new classes of oral antidiabetic agents play an increasing role in the management of type 2 diabetes, dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) and sodiumglucose cotransporters ... [more ▼]

Summary : Two new classes of oral antidiabetic agents play an increasing role in the management of type 2 diabetes, dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) and sodiumglucose cotransporters type 2 (SGLT2) inhibitors (gliflozins). After failure of a monotherapy with metformin (first pharmacological choice in type 2 diabetes), both may offer an alternative to the add-on of a sulphonylurea, especially in patients at risk of hypoglycaemia. However, the choice between a DPP-4 inhibitor and a SGLT2 inhibitor is not easy and should be oriented based upon the individual patient characteristics. The arguments in favour of one or another pharmacological class are discussed, considering a clinical case of a patient with coronary heart disease and type 2 diabetes not well controlled with metformin. [less ▲]

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See detailEtude transfrontalière des besoins de formation en Education Thérapeutique du Patient souffrant de diabète et/ou d’obésité pour le personnel médical et paramédical : enquête par méthode du groupe nominal
Pétré, Benoît ULg; Ketterer, Frédéric ULg; Vanmeerbeek, Marc ULg et al

in Presse Médicale (2016), 45(10), 351-361

INTRODUCTION: The design of continuous training programs in therapeutic patient education (ETP) should be inspired by needs shown by the professionals concerned in terms of mobilization or acquisition of ... [more ▼]

INTRODUCTION: The design of continuous training programs in therapeutic patient education (ETP) should be inspired by needs shown by the professionals concerned in terms of mobilization or acquisition of skills in this domain. The objective of this study is to analyze needs expressed by healthcare professionals (HP) involved in patients' management presenting a type 2 diabetes (T2D) and/or obesity and to compare them with the existing recommendations. METHODS: One hundred and five PS (general practitioners, dietitians and nurses) of 3 frontier regions of French-speaking European countries (France, Belgium and Grand duchy of Luxembourg) were questioned in 12 monodisciplinary groups according to the technique of the nominal group. Needs expressed by the participants were classified in the categories of the reference table of skills to dispense TPE (National Institute for Health Prevention and Education [INPES], 2013). RESULTS/DISCUSSION: Among needs expressed by HP, 52 % of the votes targeted relational skills, 10 % of the skills relative to the biomedical techniques, 20 % of the skills relative to the educational techniques and 11 %, those of organization and the coordination. Seven percent of the proposals were out of the categories of the INPES. Results do not allow to establish profiles of skills according to the studied region or profession. The recognition of the TPE by the French legislation does not seem to influence in a major way the data. CONCLUSION: The needs expressed by PS in the context of this study are focused on the relation HP/patient that is the heart of the TPE. It would however be necessary to raise awareness among HP in the acquisition of the other skills which concern in particular the animation of group, the interprofessional coordination, the consideration of the environment or more generally the procedures. [less ▲]

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See detailLE MÉDICAMENT DU MOIS Dapagliflozine (Forxiga®) Inhibiteur des cotransporteurs rénaux SGLT2, nouvel agent anti-hyperglycémiant dans le diabète de type 2
SCHEEN, André ULg

in Revue Médicale de Liège (2016), 71(10), 463-469

Résumé : La dapagliflozine, un inhibiteur spécifique des cotransporteurs sodium-glucose de type 2 (SGLT2), inhibe la réabsorption tubulaire rénale du glucose et accroît la gluco¬surie. Il en résulte une ... [more ▼]

Résumé : La dapagliflozine, un inhibiteur spécifique des cotransporteurs sodium-glucose de type 2 (SGLT2), inhibe la réabsorption tubulaire rénale du glucose et accroît la gluco¬surie. Il en résulte une diminution de la glycémie et du taux d’hémoglobine glyquée (HbA1c), avec un risque faible d’hypo¬glycémie, une perte pondérale et une diminution de la pression artérielle. L’efficacité sur la réduction du taux d’HbA1c est d’autant plus importante que l’hyperglycémie est élevée, mais elle diminue en cas d’insuffisance rénale. Les infections géni¬tales mycotiques sont plus fréquentes, surtout chez la femme, alors que l’augmentation des infections urinaires basses n’est que marginale. La dapagliflozine (Forxiga®), commercialisée à la dose de 10 mg une fois par jour, est indiquée pour le trai¬tement du diabète de type 2 et remboursée en Belgique, sous conditions, en ajout à la metformine, un sulfamide ou le répa-glinide, une association metformine-sulfamide/répaglinide ou une insuline basale avec au moins un antidiabétique oral. Des données préliminaires ne démontrent pas d’augmentation du risque cardiovasculaire par rapport au comparateur et suggèrent même une protection cardiovasculaire et rénale, à confirmer dans l’essai DECLARE, une grande étude prospec¬tive contrôlée actuellement en cours chez des patients diabé¬tiques de type 2 à haut risque cardiovasculaire. [less ▲]

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See detailProtection cardiovasculaire et rénale du patient diabétique de type 2 : le point après EMPA-REG OUTCOME et LEADER
SCHEEN, André ULg; PIERARD, Luc ULg; KRZESINSKI, Jean-Marie ULg et al

in Revue Médicale de Liège (2016), 71(09), 376-381

Summary : Type 2 diabetes (T2D), often associated with arterial hypertension, represents a high risk of cardiovascular disease and nephropathy. Two clinical trials demonstrate the superiority versus a ... [more ▼]

Summary : Type 2 diabetes (T2D), often associated with arterial hypertension, represents a high risk of cardiovascular disease and nephropathy. Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with T2D and high cardiovascular risk : empagliflozin, an inhibitor of sodium-glucose type 2 (SGLT2) cotransporters, in EMPA-REG OUTCOME and liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) receptors, in LEADER. Both medications showed a significant reduction in major cardiovascular events (-14 and -13 %, respectively), cardiovascular mortality (-38 and -22%), all-cause mortality (-32 and -15 %) and renal events (-39 et -22 %). The underlying protective mechanisms remain controverted. Ongoing studies should allow to decide whether the benefits are specific to each molecule or may be attributed to a class effect. [less ▲]

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See detailLa vignette diagnostique de l’étudiant Mise au point d’une suspicion de malaise hypoglycémique chez une personne adulte non diabétique
SCHEEN, André ULg; PAQUOT, Nicolas ULg; LEFEBVRE, Pierre ULg

in Revue Médicale de Liège (2016), 71(09), 407-413

Résumé : La survenue de malaises est souvent attribuée à une hypoglycémie chez des personnes non diabétiques et, a priori, sans autre problème de santé. Ce diagnostic est, cependant, souvent galvaudé, car ... [more ▼]

Résumé : La survenue de malaises est souvent attribuée à une hypoglycémie chez des personnes non diabétiques et, a priori, sans autre problème de santé. Ce diagnostic est, cependant, souvent galvaudé, car habituellement non clairement démontré. Le diagnostic d’hypoglycémie doit se faire de façon structurée en se basant sur la triade de Whipple. Tout d’abord, l’anamnèse doit rechercher les symptômes évocateurs d’hypoglycémie, adrénergiques et neuroglucopéniques. Ensuite, l’hypoglycémie doit être authentifiée par une mesure d’une valeur basse au moment d’un malaise. Enfin, s’il s’agit bien d’une hypoglycémie, le malaise doit disparaître rapidement après resucrage. Une fois le diagnostic posé sur la base de cette triade, l’anamnèse doit faire préciser, outre la sévérité des malaises, leur chronologie, après les repas ou à jeun, ce qui oriente vers une hypoglycémie réactive, fonctionnelle, ou vers une hypoglycémie d’origine organique (insulinome). Des examens complémentaires, faisant d’abord appel à la biologie clinique, ensuite éventuellement à l’imagerie médicale, permettront de, non seulement confirmer le diagnostic d’hypoglycémie, mais aussi d’en préciser l’origine, ce qui orientera la stratégie thérapeutique. [less ▲]

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See detailThe role of biochemical of bone turnover markers in osteoporosis and metabolic bone disease: a consensus paper of the Belgian Bone Club.
Cavalier, Etienne ULg; Bergmann, P.; Bruyère, Olivier ULg et al

in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA (2016), 27

The exact role of biochemical markers of bone turnover in the management of metabolic bone diseases remains a topic of controversy. In this consensus paper, the Belgian Bone Club aimed to provide a state ... [more ▼]

The exact role of biochemical markers of bone turnover in the management of metabolic bone diseases remains a topic of controversy. In this consensus paper, the Belgian Bone Club aimed to provide a state of the art on the use of these biomarkers in different clinical or physiological situations like in postmenopausal women, osteoporosis in men, in elderly patients, in patients suffering from bone metastasis, in patients with chronic renal failure, in pregnant or lactating women, in intensive care patients, and in diabetics. We also gave our considerations on the analytical issues linked to the use of these biomarkers, on potential new emerging biomarkers, and on the use of bone turnover biomarkers in the follow-up of patients treated with new drugs for osteoporosis. [less ▲]

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See detailRelations entre neuropathie autonome cardiaque (NAC), pression pulsée (PP) et insuffisance rénale chronique (IRC) chez le patient diabétique de type 2 (DT2)
PHILIPS, Jean-Christophe ULg; MARCHAND, Monique ULg; SCHEEN, André ULg

Poster (2016, March)

Objectifs : Ce travail étudie les relations entre trois complications diabétiques, la NAC, l’élévation de PP (marqueur de rigidité artérielle) et la diminution du débit de filtration glomérulaire (DFG ... [more ▼]

Objectifs : Ce travail étudie les relations entre trois complications diabétiques, la NAC, l’élévation de PP (marqueur de rigidité artérielle) et la diminution du débit de filtration glomérulaire (DFG) chez le patient DT2. Patients et méthodes : L’étude comprend 79 patients DT2 (53H/26F; 56±8 années; 11±8 années de DT2; IMC 28,4±4,6 kg/m²) analysés par enregistrement continu de la pression artérielle (PA) et de la fréquence cardiaque (appareil Finapres) lors d’un test postural standardisé. Le gain baro-réflexe (GBR, indice de NAC) correspond à la pente de la relation entre les espaces R-R et PA systolique (PAS) lors du redressement accroupi-debout. PP est analysée pendant tout le test et par son augmentation durant l’accroupissement (delta PP). DFG est estimé par la formule MDRD au début puis après un suivi moyen de 12±5 ans. Résultats : Les valeurs initiales sont : HbA1c : 8,8± 1,7%; DFG : 86±25 ml/min ; PP : 62±10 mmHg; BRG : 1,8±1,4 msec/mmHg. DFG est inversement corrélé à l’âge (r=-0,317; p=0,020), très positivement corrélé avec GBR (r=0,453; p=0,008), sans corrélation significative avec HbA1c (r=-0,023; p=0,935) ni avec PAS, PP ou encore delta PP (r=-0,206; p=0,114; NS). La diminution de DFG (-12±23 ml/min) lors du suivi de 12 ans n’a pu être corrélée de façon significative aux valeurs initiales et finales d’HbA1c, ni aux valeurs initiales de GBR (et d’autres marqueurs de NAC) ou de PA, même si la relation est proche de la signification pour delta PP (r=0,20; p=0,060). Conclusion : La forte relation initiale entre DFG et GBR suggère que IRC et NAC sont aggravées de façon conjointe et, possiblement, qu’une des deux complications influence l’autre. L’absence de toute corrélation entre la chute ultérieure de DFG et les autres paramètres initiaux peut s’expliquer par l’origine multifactorielle de la progression de l’IRC chez le patient DT2. [less ▲]

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See detailAntihyperglycémiants, antihypertenseurs et hypolipidémiants : comparaison des effets sur la mortalité et la morbidité cardiovasculaire chez le patient diabétique de type 2
SCHEEN, André ULg

Poster (2016, March)

Introduction : Réduire le risque de mortalité et morbidité cardiovasculaire (CV) chez le patient diabétique de type 2 (DT2) est primordial, mais les effets protecteurs semblent différents selon le mode ... [more ▼]

Introduction : Réduire le risque de mortalité et morbidité cardiovasculaire (CV) chez le patient diabétique de type 2 (DT2) est primordial, mais les effets protecteurs semblent différents selon le mode d’intervention pharmacologique étudié. Patients et méthodes : Les données de mortalité (totale et CV) et morbidité (infarctus du myocarde ou IDM, accidents vasculaires cérébraux ou AVC) rapportées (réduction du risque relatif) dans les essais ayant testé un traitement anti-hyperglycémiant sont comparées avec les résultats publiés dans deux méta-analyses concernant les hypolipidémiants et les anti-hypertenseurs consacrées au DT2. Résultats : Les antihypertenseurs réduisent les IDM (-12%) et la mortalité globale (-13%) de façon comparable, et diminuent davantage les AVC (-27%). Les hypolipidémiants diminuent davantage les IDM (- 22%) et les AVC (-21%) que la mortalité globale (-9%) (ou la mortalité CV : - 13%). Les données concernant les antihyperglycémiants diffèrent considérablement selon les médications testées. L’insuline et les sulfamides (UKPDS) réduisent plus les IDM (- 21%) que la mortalité totale (-8%), mais augmentent les AVC (+ 14%). La metformine (UKPDS) réduit, de façon comparable, les IDM (-39%), les AVC (-41%) et la mortalité totale (-36%). La pioglitazone (PROactive) diminue davantage les IDM (-17%) et les AVC (-19%) que la mortalité (-4%). Les gliptines (combinaison de SAVOR TIMI 53, EXAMINE, TECOS) ont montré des effets globalement neutres sur la mortalité totale (0%), les IDM (-2%) et les AVC (-1%). L’empagliflozine (EMPA-REG OUTCOME) se singularise par un effet favorable nettement plus marqué sur la mortalité totale (-32 %) et CV (- 38%) que sur les IDM (-13%) ou les AVC (+18%). Conclusion : Les discordances observées suggèrent l’implication de mécanismes protecteurs différents selon les interventions testées. EMPA-REG OUTCOME, le seul essai démontrant un effet plus marqué sur la mortalité que sur les événements CV, suggère un mécanisme propre de l’inhibiteur des SGLT2. [less ▲]

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See detailQuelle est la stratégie idéale pour traiter l’hyperglycémie du diabète de type 2 ?
SCHEEN, André ULg

in Médecine des Maladies Métaboliques (2016), 10(2), 91-93

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See detailLe médicament du mois. Le dulaglutide (Trulicity®) : Nouvel agoniste des récepteurs du Glucagon-Like Peptide-1 en injection hebdomadaire pour traiter le diabète de type 2
SCHEEN, André ULg

in Revue Médicale de Liège (2016), 71

Summary : Dulaglutide (Trulicity®) is a new once-weekly agonist of Glucagon-Like Peptide-1 (GLP-1) receptors indicated in the treatment of type 2 diabetes. Phase III clinical trials in AWARD programme ... [more ▼]

Summary : Dulaglutide (Trulicity®) is a new once-weekly agonist of Glucagon-Like Peptide-1 (GLP-1) receptors indicated in the treatment of type 2 diabetes. Phase III clinical trials in AWARD programme demonstrated the efficacy and safety of dulaglutide in patients with type 2 diabetes treated by diet and exercise, metformin, a combination of metformin and a sulfonylurea or metformin and pioglitazone or even by supplements of prandial insulin. In the AWARD programme, dulaglutide (subcutaneous 0.75 or 1.5 mg once weekly) exerted a greater glucose-lowering activity than metformin, sitagliptin, exenatide or insulin glargine, and was non-inferior to liraglutide 1.8 mg once daily. Dulaglutide is currently reimbursed in Belgium after failure of and in combination with a dual oral therapy with metformin and a sulfonylurea or metformin and pioglitazone. [less ▲]

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See detailLa vignette diagnostique de l’étudiant. L’importance du facteur temps et de la chronologie des événements dans l’anamnèse médicale
SCHEEN, André ULg

in Revue Médicale de Liège (2016), 71

Summary : Medical history taking represents a key step in the diagnostic approach. A structured interview with a special attention to the chronology of events is mandatory. The medical student often fails ... [more ▼]

Summary : Medical history taking represents a key step in the diagnostic approach. A structured interview with a special attention to the chronology of events is mandatory. The medical student often fails to use the information on time in an optimal way. The aim of this article is to draw the attention on a few key elements, especially the age of the patient, the duration of symptoms, the time of occurrence of complaints within the 24h period and, finally, how to interpret the simultaneous or sequential occurrence of two (or more) events. [less ▲]

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See detailLe médicament du mois. Insuline glargine 300 U/mL (Toujeo®)
SCHEEN, André ULg

in Revue Médicale de Liège (2016), 71

Summary : This article presents a new formulation of insulin glargine concentrated at 300 U/mL (Gla-300). It is commercialized under the trade name of Toujeo® in an optimized pre-filled SoloStar™ pen for ... [more ▼]

Summary : This article presents a new formulation of insulin glargine concentrated at 300 U/mL (Gla-300). It is commercialized under the trade name of Toujeo® in an optimized pre-filled SoloStar™ pen for the treatment of type 1 and type 2 diabetes in adults. Besides a threefold higher concentration compared to the classical insulin Lantus® (100 U/mL or Gla-100), both pharmacokinetic and pharmacodynamic profiles of Gla-300 are flatter and longer (more than 24 hours) and have a lesser intra-/inter-variability, which makes them more reproducible. Overall, Toujeo® offers the same hypoglycaemic efficacy and the same safety profile when compared with Lantus®. However, a lower risk of hypoglycaemia, especially at night, a slightly smaller weight gain and a better flexibility in the time of injection have been reported. The two insulin formulations are not bioequivalent and the daily insulin requirement is slightly higher with insulin Gla-300 than with insulin Gla-100. The shift from an already available basal insulin towards Toujeo® may require a dose adjustment and a reinforcement of blood glucose monitoring. [less ▲]

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See detailPharmacokinetic Characteristics and Clinical Efficacy of an SGLT2 Inhibitor Plus DPP-4 Inhibitor Combination Therapy in Type 2 Diabetes.
Scheen, André ULg

in Clinical Pharmacokinetics (2016)

Type 2 diabetes (T2D) generally requires a combination of several pharmacological approaches to control hyperglycaemia. Combining a sodium-glucose cotransporter type 2 inhibitor (SGLT2I, also known as ... [more ▼]

Type 2 diabetes (T2D) generally requires a combination of several pharmacological approaches to control hyperglycaemia. Combining a sodium-glucose cotransporter type 2 inhibitor (SGLT2I, also known as gliflozin) and a dipeptidyl peptidase-4 inhibitor (DPP-4I, also known as gliptin) appears to be an attractive strategy because of complementary modes of action. This narrative review analyzes the pharmacokinetics and clinical efficacy of different combined therapies with an SGLT2I (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, tofogliflozin) and DPP-4I (linagliptin, saxagliptin, sitagliptin, teneligliptin). Drug-drug pharmacokinetic interaction studies do not show any significant changes in peak concentrations (C max) and total exposure (area under the curve of plasma concentrations [AUC]) of either drug when they were administered together orally compared with corresponding values when each of them was absorbed alone. Two fixed-dose combinations (FDCs) are already available (dapagliflozin-saxagliptin, empagliflozin-linagliptin) and others are in development (ertugliflozin-sitagliptin). Preliminary results show bioequivalence of the two medications administered as FDC tablets when compared with coadministration of the individual tablets. Dual therapy is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin. SGLT2I and DPP-4I could be used as initial combination or in a stepwise approach. The additional glucose-lowering effect appears to be more marked when a gliflozin is added to a gliptin than when a gliptin is added to a gliflozin. Combining the two pharmacological options is safe and does not induce hypoglycaemia. [less ▲]

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See detailBody image discrepancy and subjective norm as mediators and moderators of the relationship between body mass index and quality of life
Pétré, Benoît ULg; Scheen, André ULg; ziegler, olivier et al

in Patient Preference and Adherence (2016), 10

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See detailReappraisal of the diuretic effect of empagliflozin in the EMPA-REG OUTCOME trial: Comparison with classic diuretics.
Scheen, André ULg

in Diabètes & Métabolism (2016)

AIMS: Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has been associated with a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes and ... [more ▼]

AIMS: Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has been associated with a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes and antecedents of cardiovascular disease. This effect was attributed to a diuretic (haemodynamic) rather than metabolic (antiatherogenic) effect. The aim of this review is to offer arguments that either support or challenge this 'diuretic hypothesis'. METHODS: The literature was scrutinized to: (1) examine the diuretic effects of SGLT2 inhibitors vs. hydrochlorothiazide as the reference diuretic; (2) analyze the effects of classic diuretics on cardiovascular outcomes and mortality in diabetic patients; and (3) reconsider some of the specific analyses of the EMPA-REG OUTCOME trial possibly related to a diuretic effect. RESULTS: The diuretic effect of empagliflozin has so far been poorly investigated, although SGLT2 inhibitors have actions distinct from those of classic diuretics. The effects of thiazide-like diuretics on cardiovascular and overall mortality have been limited in diabetic patients with hypertension, whereas the effects of mineralocorticoid receptor antagonists in subgroups of diabetic patients with heart failure were more impressive, but still largely inferior to those reported in EMPA-REG, where relative reductions in mortality with empagliflozin were observed in diabetic patients with or without heart failure, arterial hypertension, renal impairment or diuretic background therapy. CONCLUSION: Although the diuretic hypothesis was put forward to explain the remarkable reduction in mortality with empagliflozin in EMPA-REG, the available results do not support a major contribution of this mechanism, unless the specific diuretic effect of SGLT2 inhibitors turns out to be markedly different from those of classic diuretics. [less ▲]

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See detailEffects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME.
Scheen, André ULg

in Diabetes Research & Clinical Practice (2016), 121

Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of ... [more ▼]

Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of cardiovascular disease in the EMPA-REG OUTCOME trial. This effect has been attributed to a hemodynamic rather than a metabolic effect, partly due to the osmotic/diuretic effect of empagliflozin and to the reduction in arterial blood pressure. The present review will: (1) summarize the results of specific studies having tested the blood pressure lowering effects of SGLT2 inhibitors; (2) describe the results of meta-analyses of trials having evaluated the effects on mortality and cardiovascular outcomes of lowering blood pressure in patients with T2D, with a special focus on baseline and target blood pressures; (3) compare the cardiovascular outcome results in EMPA-REG OUTCOME versus other major trials with antihypertensive agents in patients with T2D; and (4) evaluate post-hoc analyses from EMPA-REG OUTCOME, especially subgroups of patients of special interest regarding the blood pressure lowering hypothesis. Although BP reduction associated to empagliflozin therapy may partly contribute to the benefits reported in EMPA-REG OUTCOME, other mechanisms most probably play a greater role in the overall CV protection and reduction in mortality observed in this trial. [less ▲]

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