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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 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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See detailNew hope for glucokinase activators in type 2 diabetes?
Scheen, André ULiege

in Lancet Diabetes and Endocrinology (2018), 122((10)), 1439-1459

Cardiovascular disease (CVD) is a major challenge in the management of type 2 diabetes mellitus. Glucose-lowering agents that reduce the risk of major cardiovascular events would be considered a major ... [more ▼]

Cardiovascular disease (CVD) is a major challenge in the management of type 2 diabetes mellitus. Glucose-lowering agents that reduce the risk of major cardiovascular events would be considered a major advance, as recently reported with liraglutide and semaglutide, 2 glucagon-like peptide-1 receptor agonists, and with empagliflozin and canagliflozin, 2 SGLT-2 (sodium-glucose cotransporter type 2) inhibitors, but not with DPP-4 (dipeptidyl peptidase-4) inhibitors. The present review is devoted to CV effects of new oral glucose-lowering agents. DPP-4 inhibitors (gliptins) showed some positive cardiac and vascular effects in preliminary studies, and initial data from phase 2 to 3 clinical trials suggested a reduction in major cardiovascular events. However, subsequent CV outcome trials with alogliptin, saxagliptin, and sitagliptin showed noninferiority but failed to demonstrate any superiority compared with placebo in patients with type 2 diabetes mellitus and high CV risk. An unexpected higher risk of hospitalization for heart failure was reported with saxagliptin. SGLT-2 inhibitors (gliflozins) promote glucosuria, thus reducing glucose toxicity and body weight, and enhance natriuresis, thus lowering blood pressure. Two CV outcome trials in type 2 diabetes mellitus patients mainly in secondary prevention showed remarkable positive results. Empagliflozin in EMPA-REG-OUTCOME (EMPAgliflozin Cardiovascular OUTCOME Events in Type 2 Diabetes Mellitus Patients) reduced major cardiovascular events, CV mortality, all-cause mortality, and hospitalization for heart failure. In CANVAS (Canagliflozin Cardiovascular Assessment Study), the reduction in CV mortality with canagliflozin failed to reach statistical significance despite a similar reduction in major cardiovascular events. The underlying protective mechanisms of SGLT-2 inhibitors remain unknown and both hemodynamic and metabolic explanations have been proposed. CVD-REAL studies (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors; with the limitation of an observational approach) suggested that these favorable results may be considered as a class effect shared by all SGLT-2 inhibitors (including dapagliflozin) and be extrapolated to a larger population of patients with type 2 diabetes mellitus in primary prevention. Ongoing CV outcome trials with other DPP-4 (linagliptin) and SGLT-2 (dapagliflozin, ertugliflozin) inhibitors should provide additional information about CV effects of both pharmacological classes. [less ▲]

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See detailEffects of SGLT2 inhibitors on systemic and tissue low-grade inflammation: The potential contribution to diabetes complications and cardiovascular disease
Bonnet, Fernand ULiege; Scheen, André ULiege

in Diabetes and Metabolism (2018)

Chronic low-grade inflammation is a recognized key feature associated with type 2 diabetes mellitus (T2DM) and its complications. In prospective randomized trials, sodium-glucose cotransporter type 2 ... [more ▼]

Chronic low-grade inflammation is a recognized key feature associated with type 2 diabetes mellitus (T2DM) and its complications. In prospective randomized trials, sodium-glucose cotransporter type 2 (SGLT2) inhibitors have demonstrated benefits related to several cardiovascular and renal risk factors, including HbA1c, blood pressure, body weight, renal hyperfiltration, and improvement of cardiorenal outcomes. SGLT2 inhibitors may improve adipose tissue function and induce decreases in serum leptin, TNF-α and IL-6 while increasing adiponectin. While data on high-sensitivity C-reactive protein and other inflammatory markers are relatively scarce in humans, in animals, a number of reports have shown reductions in cytokine and chemokine concentrations in parallel with protective effects against progression of atherosclerotic lesions. Experimental findings also suggest that part of the renoprotective effects of SGLT2 inhibition may be related to anti-inflammatory actions at the kidney level. Underlying mechanisms to explain this anti-inflammatory effect are multiple, but may involve weight loss, and reduction in adipose tissue inflammation, slight increase in ketone bodies and diminution of uric acid levels or attenuation of oxidative stress. However, further studies in diabetes patients with specific assessment of inflammatory markers are still necessary to determine the specific contribution of the anti-inflammatory action of SGLT2 inhibitors to the reduction of cardiovascular and renal complications and mortality observed with this class of antidiabetic drugs. © 2018 Elsevier Masson SAS [less ▲]

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See detailEffects of glucose-lowering agents on surrogate endpoints and hard clinical renal outcomes in patients with type 2 diabetes.
Scheen, André ULiege

in Diabetes and Metabolism (2018)

Diabetic kidney disease (DKD) represents an enormous burden in patients with type 2 diabetes mellitus (T2DM). Preclinical studies using most glucose-lowering agents have suggested renal-protective effects ... [more ▼]

Diabetic kidney disease (DKD) represents an enormous burden in patients with type 2 diabetes mellitus (T2DM). Preclinical studies using most glucose-lowering agents have suggested renal-protective effects, but the proposed mechanisms of renoprotection have yet to be defined, and the promising results from experimental studies remain to be translated into human clinical findings to improve the prognosis of patients at risk of DKD. Also, it is important to distinguish effects on surrogate endpoints, such as decreases in albuminuria and estimated glomerular filtration rate (eGFR), and hard clinical endpoints, such as progression to end-stage renal disease (ESRD) and death from renal causes. Data regarding insulin therapy are surprisingly scarce, and it is nearly impossible to separate the effects of better glucose control from those of insulin per se, whereas favourable preclinical data with metformin, thiazolidinediones and dipeptidyl peptidase (DPP)-4 inhibitors are plentiful, and positive effects have been observed in clinical studies, at least for surrogate endpoints. The most favourable renal results have been reported with glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter type-2 inhibitors (SGLT2is). Significant reductions in both albuminuria and eGFR decline have been reported with these classes of glucose-lowering medications compared with placebo and other glucose-lowering agents. Moreover, in large prospective cardiovascular outcome trials using composite renal outcomes as secondary endpoints, both GLP-1RAs and SGLT2is added to standard care reduced renal outcomes combining persistent macro-albuminuria, doubling of serum creatinine, progression to ESRD and kidney-related death; however, to date, only SGLT2is have been clearly shown to reduce such hard clinical outcomes. Yet, as the renoprotective effects of SGLT2is and GLP-1RAs appear to be independent of glucose-lowering activity, the underlying mechanisms are still a matter of debate. For this reason, further studies with renal outcomes as primary endpoints are now awaited in T2DM patients at high risk of DKD, including trials evaluating the potential add-on benefits of combined GLP-1RA-SGLT2i therapies. [less ▲]

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See detailAddressing cardiovascular risk in type 2 diabetes mellitus: a report from the European Society of Cardiology Cardiovascular Roundtable.
Cosentino, Francesco; Ceriello, Antonio; Baeres, Florian M. M. et al

in European Heart Journal (2018), 0

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