Antidiabetic agents: Potential anti-inflammatory activity beyond glucose control.
Scheen, André ; ; Paquot, Nicolas
in Diabetes & metabolism (2015)
A growing body of evidence is emerging to show that abdominal obesity, the metabolic syndrome, type 2 diabetes, cardiovascular disease and microvascular diabetic complications are intimately related to ... [more ▼]
A growing body of evidence is emerging to show that abdominal obesity, the metabolic syndrome, type 2 diabetes, cardiovascular disease and microvascular diabetic complications are intimately related to chronic inflammation. These observations pave the way to the development of new pharmacological strategies that aim to reduce silent inflammation. However, besides specific anti-inflammatory agents, glucose-lowering medications may also exert anti-inflammatory effects that could contribute to improved outcomes in diabetic patients. Most studies have used metformin, an AMP-activated protein kinase (AMPK) activator, and thiazolidinediones (TZDs), which act as peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists. Both pharmacological classes (considered insulin-sparing agents or insulin sensitizers) appear to have greater anti-inflammatory activity than insulin-secreting agents such as sulphonylureas or glinides. In particular, TZDs have shown the widest range of evidence of lowered tissue (visceral fat and liver) and serum inflammation. In contrast, despite reducing postprandial hyperglycaemia, the effect of alpha-glucosidase inhibitors on inflammatory markers appears rather modest, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) and glucagon-like peptide-1 (GLP-1) receptor agonists appear more promising in this respect. These incretin-based therapies exert pleiotropic effects, including reports of anti-inflammatory activity. No human data are available so far regarding sodium-glucose cotransporter type 2 (SGLT2) inhibitors. Although they may have indirect effects due to reduced glucotoxicity, their specific mode of action in the kidneys does not suggest systemic anti-inflammatory activity. Also, in spite of the complex relationship between insulin and atherosclerosis, exogenous insulin may also exert anti-inflammatory effects. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and potential anti-inflammatory effects related to intrinsic actions of the pharmacological class. Finally, it would also be of major clinical interest to define what role the anti-inflammatory effects of these glucose-lowering agents may play in the prevention of macrovascular and microvascular diabetic complications. [less ▲]Detailed reference viewed: 28 (4 ULg)
Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease.
Esser, Nathalie ; Paquot, Nicolas ; Scheen, André
in Expert opinion on investigational drugs (2015), 24(3), 283-307
Introduction: There is a growing body of evidence to suggest that chronic silent inflammation is a key feature in abdominal obesity, metabolic syndrome, type 2 diabetes (T2DM) and cardiovascular disease ... [more ▼]
Introduction: There is a growing body of evidence to suggest that chronic silent inflammation is a key feature in abdominal obesity, metabolic syndrome, type 2 diabetes (T2DM) and cardiovascular disease (CVD). These observations suggest that pharmacological strategies, which reduce inflammation, may be therapeutically useful in treating obesity, type 2 diabetes and associated CVD. Area covered: The article covers novel strategies, using either small molecules or monoclonal antibodies. These strategies include: approaches targeting IKK-b-NF-kB (salicylates, salsalate), TNF-alpha (etanercept, infliximab, adalimumab), IL-1beta (anakinra, canakinumab) and IL-6 (tocilizumab), AMP-activated protein kinase activators, sirtuin-1 activators, mammalian target of rapamycin inhibitors and C-C motif chemokine receptor 2 antagonists. Expert opinion: The available data supports the concept that targeting inflammation improves insulin sensitivity and beta-cell function; it also ameliorates glucose control in insulin-resistant patients with inflammatory rheumatoid diseases as well in patients with metabolic syndrome or T2DM. Although promising, the observed metabolic effects remain rather modest in most clinical trials. The potential use of combined anti-inflammatory agents targeting both insulin resistance and insulin secretion appears appealing but remains unexplored. Large-scale prospective clinical trials are underway to investigate the safety and efficacy of different anti-inflammatory drugs. Further evidence is needed to support the concept that targeting inflammation pathways may represent a valuable option to tackle the cardiometabolic complications of obesity. [less ▲]Detailed reference viewed: 54 (9 ULg)
Author's Reply to De Ponti et al.: "Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus"
in Clinical pharmacokinetics (2015)Detailed reference viewed: 12 (1 ULg)
Clinical inertia in general practice, a matter of debate: a qualitative study with 114 general practitioners in Belgium.
; ; et al
in BMC family practice (2015), 16(1), 13
BackgroundPrescribing that is not concordant with guidelines is increasingly referred to as clinical inertia (CI). However, CI may be only apparent, and the absence of decision may actually reflect ... [more ▼]
BackgroundPrescribing that is not concordant with guidelines is increasingly referred to as clinical inertia (CI). However, CI may be only apparent, and the absence of decision may actually reflect appropriate inaction as a result of good clinical reasoning. Our study aimed to: (i) elucidate GPs inverted question mark beliefs regarding CI and the risk of CI in their own practice, (ii) identify modifiable provider-related factors associated with CI.MethodsWe conducted 8 group interviews with 114 general practitioners (GP) in Belgium, and used an integrated approach of thematic analysis.ResultsOur results call for a redefinition of CI, in order to take into account the GPs inverted question mark extended health-promoting role, and acknowledge that inaction or delayed action follows a process of clinical reasoning that takes into account the patients inverted question mark preferences, and that is appropriate most of the time. However, the participants in our study did acknowledge that the risk of CI exists in practice. The main factor of such a risk is when GPs feel overwhelmed and disempowered, due to characteristics of either the patients or the health care system, including contradictions between guidelines and reimbursement policies.ConclusionsAlthough situations of clinical inertia exist in practice and need to be prevented or corrected, the term clinical inertia could potentially increase the already existing gap between general practice and specialised care, whereas sustained efforts toward more collaborative work and integrated care are called for. [less ▲]Detailed reference viewed: 23 (1 ULg)
Safety of dipeptidyl peptidase-4 inhibitors for treating type 2 diabetes.
in Expert opinion on drug safety (2015), epub
Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) occupy a growing place in the armamentarium of drugs used for the management of hyperglycemia in type 2 diabetes, although some safety ... [more ▼]
Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) occupy a growing place in the armamentarium of drugs used for the management of hyperglycemia in type 2 diabetes, although some safety concerns have been raised in recent years. Areas covered: An updated review providing an analysis of available safety data (meta-analyses, randomized controlled trials, observational cohort and case-control studies and pharmacovigilance reports) with five commercialized DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, alogliptin, linagliptin). A special focus is given to overall safety profile; pancreatic adverse events (AEs) (acute pancreatitis, pancreatic cancer); overall cardiovascular safety (myocardial infarction and stroke); congestive heart failure concern and finally, safety in special populations (elderly, renal impairment). Expert opinion: The good tolerance/safety profile of DPP-4 inhibitors has been largely confirmed, including in more fragile populations (elderly, renal impairment) with almost no increased risk of infection or gastrointestinal AEs, no weight gain and a minimal risk of hypoglycemia. Although an increased risk of acute pancreatitis and pancreatic cancer was suspected, the complete set of available data appears reassuring so far. Cardiovascular safety of DPP-4 inhibitors has been proven but an unexpected increased risk of heart failure has been reported which should be confirmed in ongoing trials and better understood. Further postmarketing surveillance is recommended. [less ▲]Detailed reference viewed: 62 (7 ULg)
Pharmacodynamics, Efficacy and Safety of Sodium-Glucose Co-Transporter Type 2 (SGLT2) Inhibitors for the Treatment of Type 2 Diabetes Mellitus.
in Drugs (2015), 75(1), 33-59
Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries ... [more ▼]
Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries (dapagliflozin, canagliflozin, empagliflozin and ipragliflozin) and some others are in a late phase of development. The available SGLT2 inhibitors share similar pharmacokinetic characteristics, with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites, the absence of clinically relevant drug-drug interactions and a low renal elimination as parent drug. SGLT2 co-transporters are responsible for reabsorption of most (90 %) of the glucose filtered by the kidneys. The pharmacological inhibition of SGLT2 co-transporters reduces hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. The amount of glucose excreted in the urine depends on both the level of hyperglycaemia and the glomerular filtration rate. Results of numerous placebo-controlled randomised clinical trials of 12-104 weeks duration have shown significant reductions in glycated haemoglobin (HbA1c), resulting in a significant increase in the proportion of patients reaching HbA1c targets, and a significant lowering of fasting plasma glucose when SGLT2 inhibitors were administered as monotherapy or in addition to other glucose-lowering therapies including insulin in patients with T2DM. In head-to-head trials of up to 2 years, SGLT2 inhibitors exerted similar glucose-lowering activity to metformin, sulphonylureas or sitagliptin. The durability of the glucose-lowering effect of SGLT2 inhibitors appears to be better; however, this remains to be more extensively investigated. The risk of hypoglycaemia was much lower with SGLT2 inhibitors than with sulphonylureas and was similarly low as that reported with metformin, pioglitazone or sitagliptin. Increased renal glucose elimination also assists weight loss and could help to reduce blood pressure. Both effects were very consistent across the trials and they represent some advantages for SGLT2 inhibitors when compared with other oral glucose-lowering agents. The pharmacodynamic response to SGLT2 inhibitors declines with increasing severity of renal impairment, and prescribing information for each SGLT2 inhibitor should be consulted regarding dosage adjustments or restrictions in moderate to severe renal dysfunction. Caution is also recommended in the elderly population because of a higher risk of renal impairment, orthostatic hypotension and dehydration, even if the absence of hypoglycaemia represents an obvious advantage in this population. The overall effect of SGLT2 inhibitors on the risk of cardiovascular disease is unknown and will be evaluated in several ongoing prospective placebo-controlled trials with cardiovascular outcomes. The impact of SGLT2 inhibitors on renal function and their potential to influence the course of diabetic nephropathy also deserve more attention. SGLT2 inhibitors are generally well-tolerated. The most frequently reported adverse events are female genital mycotic infections, while urinary tract infections are less commonly observed and generally benign. In conclusion, with their unique mechanism of action that is independent of insulin secretion and action, SGLT2 inhibitors are a useful addition to the therapeutic options available for the management of T2DM at any stage in the natural history of the disease. Although SGLT2 inhibitors have already been extensively investigated, further studies should even better delineate the best place of these new glucose-lowering agents in the already rich armamentarium for the management of T2DM. [less ▲]Detailed reference viewed: 73 (1 ULg)
Etude des triades du programme EDUDORA² : mécanismes psychologiques complexes sous-jacents au surpoids et à l’obésité chez l’adolescent.
Degrange, Sophie ; PETRE, Benoit ; et al
Conference (2014, December)Detailed reference viewed: 28 (1 ULg)
Programme EDUDORA²: quelles leçons tirer de l'étude des représentations au sein de la triade patient/soignant/famille pour la prévention et le traitement du diabète et de l’obésité ?
Degrange, Sophie ; PETRE, Benoit ; et al
Poster (2014, December)Detailed reference viewed: 52 (7 ULg)
Besoins de formation en éducation thérapeutique du patient pour la prise en charge du diabète de type 2 et de l’obésité : Résultats d’une étude par groupes nominaux auprès des professionnels de santé.
Pétré, Benoît ; Ketterer, Frédéric ; Vanmeerbeek, Marc et al
Conference (2014, December)Detailed reference viewed: 78 (3 ULg)
Canagliflozine (Invokana®) : inhibiteur des cotransporteurs rénaux sglt2 pour traiter le diabète de type 2
in Revue Médicale de Liège (2014), 69(12), 692-699
Canagliflozin is an inhibitor of sodium-glucose cotransporters type 2 (SGLT2) that are present in renal tubules. This specific insulin-independent mechanism promotes glucosuria, which results in a ... [more ▼]
Canagliflozin is an inhibitor of sodium-glucose cotransporters type 2 (SGLT2) that are present in renal tubules. This specific insulin-independent mechanism promotes glucosuria, which results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA1c). Furthermore, canagliflozin promotes weight loss and lowers arterial (mainly systolic) blood pressure. Its efficacy is decreased in patients with renal insufficiency and the treatment should be stopped if estimated glomerular filtration rate is below 45 ml/min/1.73 m². Both the efficacy and safety of canagliflozin have been investigated in 24 to 104-week controlled trials versus placebo or versus an active comparator (glimepiride or sitagliptin). The mean reduction in HbA1c averages 0.75% when added to other treatments, as compared to placebo. The 100 mg dose is as active as sitagliptin 100 mg while the 300 mg canagliflozin dose is even more efficacious. Adverse events are mostly mycotic genital infections and more rarely mild urinary tract infections. Caution is required in elderly patients and the risk of volume depletion should be checked (hypotension). Hypoglycaemia may occur only in patients already treated with an insulin-secreting agent or insulin. Canagliflozin is commercialized under the trade name Invokana®, at the doses of 100 mg and 300 mg once daily, for the treatment of type 2 diabetes. [less ▲]Detailed reference viewed: 216 (6 ULg)
Comment je traite … Recommandations pour interrompre un traitement médicamenteux
in Revue Médicale de Liège (2014), 69(12), 644-649
L’interruption d’un traitement pharmacologique est une situation clinique fréquente qui peut paraître plus simple à gérer que l’instauration d’un nouveau traitement, mais qui impose néanmoins de remplir ... [more ▼]
L’interruption d’un traitement pharmacologique est une situation clinique fréquente qui peut paraître plus simple à gérer que l’instauration d’un nouveau traitement, mais qui impose néanmoins de remplir certaines conditions et de respecter certaines précautions : 1) pouvoir expliciter les raisons qui justifient l’arrêt du traitement; 2) vérifier qu’il n’y a pas de danger à interrompre le traitement (même si cette interruption est transitoire); 3) savoir comment gérer au mieux l’arrêt de la thérapeutique, en particulier choisir entre une interruption immédiate et une décroissance posologique progressive; et, enfin, 4) assurer un suivi approprié du patient dûment informé chez lequel le traitement vient d’être stoppé. [less ▲]Detailed reference viewed: 23 (2 ULg)
Quelles compétences pour le développement de l’Education Thérapeutique du patient (ETP) dans le domaine du diabète de type 2 et de l’obésité ? Le point de vue des soignants par la technique du groupe nominal.
Pétré, Benoît ; Ketterer, Frédéric ; Vanmeerbeek, Marc et al
Conference (2014, November)Detailed reference viewed: 58 (2 ULg)
Comment je traite … Recommandations pour surveiller et optimiser un traitement médicamenteux en cours
in Revue Médicale de Liège (2014), 69(11), 581-585
Any pharmacological treatment should ideally be effective and safe. The supervision of an ongoing therapy should control that individualized goals are reached while tolerance and safety are present. In ... [more ▼]
Any pharmacological treatment should ideally be effective and safe. The supervision of an ongoing therapy should control that individualized goals are reached while tolerance and safety are present. In case of not reaching the predefined objectives, the causes of failure should first be screened (for instance, exclusion of poor patient compliance), and the treatment should be then optimized : dose adjustment, add-on of another drug (if possible synergistic combination) and/or shift to a more effective pharmacological therapy. In some cases, therapeutic monitoring may be useful or even mandatory in order to better adjust drug dosing and thus guarantee both efficacy and safety. [less ▲]Detailed reference viewed: 48 (7 ULg)
Le médicament du mois Combinaison fixe périndopril-indapamide-amlodipine (Triplixam®) pour le traitement de l’hypertension artérielle
SCHEEN, André ; LANCELLOTTI, Patrizio ; KRZESINSKI, Jean-Marie
in Revue Médicale de Liège (2014), 69(10), 565-570
Triplixam® is a fixed dose combination of three well known antihypertensive agents, with complementary activities, to control blood pressure in patients with arterial hypertension : perindopril, an ... [more ▼]
Triplixam® is a fixed dose combination of three well known antihypertensive agents, with complementary activities, to control blood pressure in patients with arterial hypertension : perindopril, an angiotensin converting enzyme inhibitor, indapamide, un diuretic whith thiazide-like effects but also specific properties, and amlodipine, a long-acting calcium antagonist of the dihydropyridine family. The potential synergic action allows better control of blood pressure with once daily administration, while limiting the incidence of adverse events. Various presentations with different dosages are available to facilitate individualized therapy. Warnings and precautions for use of every molecule should of course be respected. Such a fixed dose combination should contribute to limit clinical inertia and to improve therapeutic compliance. [less ▲]Detailed reference viewed: 260 (4 ULg)
Comment je traite … recommandations pour instaurer un traitement medicamenteux
in Revue Médicale de Liège (2014), 69(10), 526-530
Initiating a new pharmacological therapy is an important step in the global medical approach. Such a decision is the final step of a careful reasoning and should respect some rules in order to guarantee ... [more ▼]
Initiating a new pharmacological therapy is an important step in the global medical approach. Such a decision is the final step of a careful reasoning and should respect some rules in order to guarantee the best efficacy, but also safety for the patient. Clinical inertia should be avoided, but the essential principles of the evidence based medicine should also be taken into account. This concise article summarizes the main fundamental rules and cautions that should be respected by any clinician when initiating a new pharmacological therapy. [less ▲]Detailed reference viewed: 18 (2 ULg)
Obese subjects involvement in a population-based survey: the use of information and communication technologies (ICT) to avoid stigmatization
Pétré, Benoît ; Donneau, Anne-Françoise ; Crutze, Céline et al
in Quality of Life Research (2014)Detailed reference viewed: 42 (25 ULg)
Comment je traite ... Le choix entre un sulfamide hypoglycémiant et une gliptine pour traiter le diabète de type 2
in Revue Médicale de Liège (2014), 69(9), 476-484
The pharmacological therapy of hyperglycaemia in type 2 diabetes becomes increasingly complex. After failure of metformin monotherapy, several choices are possible. In clinical practice, the most common ... [more ▼]
The pharmacological therapy of hyperglycaemia in type 2 diabetes becomes increasingly complex. After failure of metformin monotherapy, several choices are possible. In clinical practice, the most common dilemma is to choose between adding a sulphonylurea or adding a dipeptidyl peptidase-4 inhibitor (gliptin). This review analyses the arguments in favour of one or the other pharmacological option, based upon criteria of efficacy, tolerance, safety, easiness of use, use in at risk populations and, last but not least, cost of therapy. In general, a patient-centered approach is recommended with an individualization of the therapy in function of the characteristics of each patient with the aim to obtain the best benefits/risks ratio, at an affordable cost. [less ▲]Detailed reference viewed: 58 (3 ULg)
Free fatty acids as modulators of the NLRP3 inflammasome in obesity / type 2 diabetes
Legrand-Poels, Sylvie ; Esser, Nathalie ; L'Homme, Laurent et al
in Biochemical Pharmacology (2014)Detailed reference viewed: 65 (11 ULg)
Les objectifs de la formation des soignants en Education Thérapeutique du Patient : une proposition
Pétré, Benoît ; Guillaume, Michèle ; et al
Conference (2014, September)Detailed reference viewed: 49 (9 ULg)
Psychological mechanisms underlying overweight and obesity during adolescence: Triads study from the EDUDORA² project.
Degrange, Sophie ; PETRE, Benoit ; et al
in Appetite (2014, May), 76Detailed reference viewed: 44 (3 ULg)