References of "SCHEEN, André"
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See detailPharmacothérapie du sujet âgé: Primum non nocere!
Scheen, André ULg

in Revue medicale de Liege (2014), 69(5-6), 282-6

Elderly patients, having various chronic diseases, are generally exposed to polypharmacy that may lead to potential adverse events. The latter may be explained by pharmacokinetic and pharmacodynamic ... [more ▼]

Elderly patients, having various chronic diseases, are generally exposed to polypharmacy that may lead to potential adverse events. The latter may be explained by pharmacokinetic and pharmacodynamic particularities that render elderly individuals more vulnerable when exposed to certain medications. Recruitment of elderly patients in clinical trials is often limited, so that it is not always easy to determine the real benefit/risk ratio of pharmacotherapy in this population. Obviously, iatrogenicity is quite frequent. Therefore, in front of unexplained alterations of health status in an elderly individual, the physician should consider the possibility of a drug adverse effect. Because of this situation, the physician should envisage a reasonable drug prescription in an elderly patient. Especially, not only the initiation of drug therapy should be carefully analyzed, but also the opportunity to eventually stop a medication that may be useless or even dangerous. Rather polypharmacy per se, it is the inappropriate prescription that should be avoided in the elderly. [less ▲]

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See detailPharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor.
Scheen, André ULg

in Clinical pharmacokinetics (2014), 53(3), 213-25

Empagliflozin is an orally active, potent and selective inhibitor of sodium glucose co-transporter 2 (SGLT2), currently in clinical development to improve glycaemic control in adults with type 2 diabetes ... [more ▼]

Empagliflozin is an orally active, potent and selective inhibitor of sodium glucose co-transporter 2 (SGLT2), currently in clinical development to improve glycaemic control in adults with type 2 diabetes mellitus (T2DM). SGLT2 inhibitors, including empagliflozin, are the first pharmacological class of antidiabetes agents to target the kidney in order to remove excess glucose from the body and, thus, offer new options for T2DM management. SGLT2 inhibitors exert their effects independently of insulin. Following single and multiple oral doses (0.5-800 mg), empagliflozin was rapidly absorbed and reached peak plasma concentrations after approximately 1.33-3.0 h, before showing a biphasic decline. The mean terminal half-life ranged from 5.6 to 13.1 h in single rising-dose studies, and from 10.3 to 18.8 h in multiple-dose studies. Following multiple oral doses, increases in exposure were dose-proportional and trough concentrations remained constant after day 6, indicating a steady state had been reached. Oral clearance at steady state was similar to corresponding single-dose values, suggesting linear pharmacokinetics with respect to time. No clinically relevant alterations in pharmacokinetics were observed in mild to severe hepatic impairment, or in mild to severe renal impairment and end-stage renal disease. Clinical studies did not reveal any relevant drug-drug interactions with several other drugs commonly prescribed to patients with T2DM, including warfarin. Urinary glucose excretion (UGE) rates were higher with empagliflozin versus placebo and increased with dose, but no relevant impact on 24-h urine volume was observed. Increased UGE resulted in proportional reductions in fasting plasma glucose and mean daily glucose concentrations. [less ▲]

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See detailMetabolic effects of SGLT-2 inhibitors beyond increased glucosuria: A review of the clinical evidence.
Scheen, André ULg; Paquot, Nicolas ULg

in Diabetes & metabolism (2014), 40(6 Suppl 1), 4-11

Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin) are new glucose-lowering agents that exert their therapeutic activity independently of insulin by ... [more ▼]

Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin) are new glucose-lowering agents that exert their therapeutic activity independently of insulin by facilitating glucose excretion through the kidneys. However, this simple renal mechanism that results in sustained glucose urinary loss leads to more complex indirect metabolic effects. First, by reduction of chronic hyperglycaemia and attenuation of glucose toxicity, SGLT-2 inhibitors can improve both insulin secretion by beta cells and peripheraltissue insulin sensitivity. In the case of canagliflozin, because of low-potency SGLT1 inhibition, a non-renal (intestinal) effect may also be considered, which may contribute to better control of postprandial hyperglycaemia, although this contribution remains to be better analyzed in humans. Second, chronic glucose loss most probably leads to compensatory mechanisms. One of them, although not well evidenced in humans, might involve an increase in energy intake, an effect that may limit weight loss in the long run. Another could be an increase in endogenous glucose production, most probably driven by increased glucagon secretion, which may somewhat attenuate the glucoselowering effect. Nevertheless, despite these compensatory mechanisms and most probably because of the positive effects of the reduction in glucotoxicity, SGLT-2 inhibitors exert clinically relevant glucose-lowering activity while promoting weight loss, a unique dual effect among oral antidiabetic agents. Furthermore, the combination of SGLT-2 inhibitors with other drugs that either have anorectic effects (such as incretin-based therapies) or reduce hepatic glucose output (like metformin) and, thus, may dampen these two compensatory mechanisms appears appealing for the management of type 2 diabetes mellitus. [less ▲]

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See detailInteret d'une combinaison agoniste des recepteurs du GLP-1 et insuline basale dans le traitement du diabete de type 2.
Scheen, André ULg; Paquot, Nicolas ULg

in Revue medicale suisse (2014), 10(439), 1549-54

The complex pathophysiology of type 2 diabetes and its natural evolution, characterized by a progressive loss of glucose control due to the exhaustion of insulin secretion, lead to consider new ... [more ▼]

The complex pathophysiology of type 2 diabetes and its natural evolution, characterized by a progressive loss of glucose control due to the exhaustion of insulin secretion, lead to consider new complementary therapeutic options. Even at the insulin-requiring stage, the addition of a glucagon-like peptide-1 (GLP-1) receptor agonist is beneficial. Besides their incretinomimetic activity (which may decrease with the loss of beta-cell mass/function), GLP-1 receptor agonists reduce glucagon secretion, slow down gastric emptying and diminish appetite through a central effect. These combined effects permit to improve glucose control, while reducing daily insulin doses, together with less weight gain (or even weight loss) and generally less hypoglycaemia. Fixed insulin glargine-lixisenatide and insulin degludec-liraglutide are currently in development. [less ▲]

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See detailPharmacokinetics and Clinical Use of Incretin-Based Therapies in Patients with Chronic Kidney Disease and Type 2 Diabetes.
Scheen, André ULg

in Clinical pharmacokinetics (2014)

The prevalence of chronic kidney disease (CKD) of stages 3-5 (glomerular filtration rate [GFR] <60 mL/min) is about 25-30 % in patients with type 2 diabetes mellitus (T2DM). While most oral antidiabetic ... [more ▼]

The prevalence of chronic kidney disease (CKD) of stages 3-5 (glomerular filtration rate [GFR] <60 mL/min) is about 25-30 % in patients with type 2 diabetes mellitus (T2DM). While most oral antidiabetic agents have limitations in patients with CKD, incretin-based therapies are increasingly used for the management of T2DM. This review analyses (1) the influence of CKD on the pharmacokinetics of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists; and (2) the efficacy/safety profile of these agents in clinical practice when prescribed in patients with both T2DM and CKD. Most DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, alogliptin) are predominantly excreted by the kidneys. Thereby, pharmacokinetic studies showed that total exposure to the drug is increased in proportion to the decline of GFR, leading to recommendations for appropriate dose reductions according to the severity of CKD. In these conditions, clinical studies reported a good efficacy and safety profile in patients with CKD. In contrast, linagliptin is eliminated by a predominantly hepatobiliary route. As a pharmacokinetic study showed only minimal influence of decreased GFR on total exposure, no dose adjustment of linagliptin is required in the case of CKD. The experience with GLP-1 receptor agonists in patients with CKD is more limited. Exenatide is eliminated by renal mechanisms and should not be given in patients with severe CKD. Liraglutide is not eliminated by the kidney, but it should be used with caution because of the limited experience in patients with CKD. Only limited pharmacokinetic data are also available for lixisenatide, exenatide long-acting release (LAR) and other once-weekly GLP-1 receptor agonists in current development. Several case reports of acute renal failure have been described with GLP-1 receptor agonists, probably triggered by dehydration resulting from gastrointestinal adverse events. However, increasing GLP-1 may also exert favourable renal effects that could contribute to reducing the risk of diabetic nephropathy. In conclusion, the already large reassuring experience with DPP-4 inhibitors in patients with CKD offers new opportunities to the clinician, whereas more caution is required with GLP-1 receptor agonists because of the limited experience in this population. [less ▲]

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See detailAlogliptin: concern about hepatotoxicity?
Scheen, André ULg

in Clinical pharmacokinetics (2014), 53(11), 1057-9

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See detailMaladies hepatiques chroniques et diabete.
Jaafar, Jaafar; de Kalbermatten, Benedicte; Philippe, Jacques et al

in Revue medicale suisse (2014), 10(433), 12541256-60

The presence of chronic liver diseases may drastically limit the use of anti-diabetic drugs. Chronic liver diseases increase insulin resistance, and in some risk groups promote the development of diabetes ... [more ▼]

The presence of chronic liver diseases may drastically limit the use of anti-diabetic drugs. Chronic liver diseases increase insulin resistance, and in some risk groups promote the development of diabetes. Therefore, antidiabetic treatment should be adapted to the severity of liver disease. However, diabetes, notably when associated with obesity and dyslipidemia, participates in the development of nonalcoholic fatty liver disease and to steato-hepatitis that may progress to cirrhosis and hepatocellular carcinoma. Other relations between diabetes and chronic liver disease will be discussed in this article. Finally, the indications and limits of each anti-diabetic therapy group will be discussed according to the degree of liver damage. [less ▲]

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See detailL'alogliptine (Vipidia): inhibiteur selectif de la DPP-4 avec une bonne securite cardiovasculaire.
Scheen, André ULg

in Revue medicale de Liege (2014), 69(7-8), 460-6

Alogliptin (Vipidia) is a new selective inhibitor of dipeptidyl peptidase-4. By potentiating insulin secretion and by inhibiting glucagon secretion, both in a glucose-dependent manner, it improves glucose ... [more ▼]

Alogliptin (Vipidia) is a new selective inhibitor of dipeptidyl peptidase-4. By potentiating insulin secretion and by inhibiting glucagon secretion, both in a glucose-dependent manner, it improves glucose control of type 2 diabetic patients, without increasing the risk of hypoglycaemia and inducing weight gain, with an excellent clinical and biological tolerance. Both efficacy and safety have been demonstrated in randomised controlled trials, in monotherapy or in combination with other oral antidiabetic agents or even insulin. These results were obtained independently of clinical or demographic patient characteristics, including in elderly subjects and in patients with renal insufficiency. However, because alogliptin is eliminated through the kidneys, the usual dose of 25 mg once daily should be reduced to 12.5 mg per day in case of moderate renal impairment and to 6.25 mg per day in case of severe renal failure. Cardiovascular safety of alogliptin has been demonstrated in a large prospective study (EXAMINE) showing non-inferiority versus placebo in type 2 diabetic patients following an acute coronary syndrome. [less ▲]

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See detailWhich incretin-based therapy for type 2 diabetes?
Scheen, André ULg

in Lancet (2014)

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See detailLe medicament du mois. Bydureon: premier agoniste des recepteurs du GLP-1 en une injection hebdomadaire (exenatide a liberation prolongee).
Scheen, André ULg

in Revue medicale de Liege (2014), 69(4), 214-9

Bydureon is a new galenic formulation (long-acting release) of exenatide, the first agonist of Glucagon-Like Peptide-1 (GLP-1) receptors having been commercialized for the management of type 2 diabetes ... [more ▼]

Bydureon is a new galenic formulation (long-acting release) of exenatide, the first agonist of Glucagon-Like Peptide-1 (GLP-1) receptors having been commercialized for the management of type 2 diabetes. The microsphere technology permits a prolonged absorption of exenatide from the subcutaneous depot, which allows one injection per week instead of two injections per day with the initial formulation of exenatide (Byetta). The clinical development programme DURATION showed that exenatide 2 mg once weekly more markedly reduces glycated haemoglobin (HbA(1c)), with a similar weight loss but a better digestive tolerance profile (less nausea and vomiting after treatment initiation), compared with the twice daily 10 microg exenatide. When compared to other glucose-lowering agents, once weekly exenatide is more efficacious than sitagliptin, pioglitazone or basal insulin (glargine or detemir), with the advantage of producing weight loss and lowering arterial blood pressure. It does not induce hypoglycaemia and does not necessarily require home blood glucose monitoring, two advantages compared with insulin therapy. Bydureon is currently only reimbursed in Belgium after failure of and in addition to metformin-sulfonylurea combination. [less ▲]

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See detailInflammation as a link between obesity, metabolic syndrome and type 2 diabetes
ESSER, Nathalie ULg; Legrand, Sylvie ULg; Piette, Jacques ULg et al

in Diabetes Research & Clinical Practice (2014)

It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic ... [more ▼]

It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic inflammatory markers are risk factors for the development of type 2 diabetes and its macrovascular complications. Adipose tissue, liver, muscle and pancreas are themselves sites of inflammation in presence of obesity. An infiltration of macrophages and other immune cells is observed in these tissues associated with a cell population shift from an anti-inflammatory to a pro-inflammatory profile. These cells are crucial for the production of pro-inflammatory cytokines, which act in an autocrine and paracrine manner to interfere with insulin signaling in peripheral tissues or induce β-cell dysfunction and subsequent insulin deficiency. Particularly, the pro-inflammatory interleukin-1β is implicated in the pathogenesis of type 2 diabetes through the activation of the NLRP3 inflammasome. The objectives of this review are to expose recent data supporting the role of the immune system in the pathogenesis of insulin resistance and type 2 diabetes and to examine various mechanisms underlying this relationship. If type 2 diabetes is an inflammatory disease, anti-inflammarory therapies could have a place in prevention and treatment of type 2 diabetes. [less ▲]

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See detailLe temps de la reflexion... a propos de la demographie medicale et de la demographie "societale".
Scheen, André ULg

in Revue medicale de Liege (2014), 69(1), 1-3

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See detailLe medicament du mois. Le lixisenatide (Lyxumia): nouvel agoniste des recepteurs du glucagon-like peptide-1 a action preferentiellement post-prandiale.
Scheen, André ULg

in Revue medicale de Liege (2014), 69(2), 102-9

Lixisenatide (Lyxumia) is a new agonist of Glucagon-Like Peptide-1 (GLP-1) receptors that is indicated in the treatment of type 2 diabetes, in one single subcutaneous daily injection of 20 microg. It ... [more ▼]

Lixisenatide (Lyxumia) is a new agonist of Glucagon-Like Peptide-1 (GLP-1) receptors that is indicated in the treatment of type 2 diabetes, in one single subcutaneous daily injection of 20 microg. It exerts an incretin effect by stimulating insulin secretion after a meal while inhibiting glucagon secretion, both in a glucose-dependent manner, which limits the risk of hypoglycaemia. In addition, it slows down gastric emptying after a meal, which contributes to reduce postprandial hyperglycaemia, especially after breakfast. Lixisenatide is currently reimbursed in Belgium after failure of a dual therapy with metformin and a sulfonylurea but also in combination with a basal insulin (with or without oral antidiabetic drugs). The latter interesting combination should tackle fasting glycaemia with basal insulin (after appropriate dose titration) and postprandial hyperglycaemia with the GLP-1 receptor agonist in a complementary manner. The consequence is a further improvement of glycated haemoglobin (HbA(1c)) varying between 0.3 and 0.9% in various studies comparing lixisenatide versus placebo. As other compounds of the class, lixisenatide induces a small weight reduction, which contrasts with the weight gain commonly observed with other antidiabetic medications (including insulin). Further studies should demonstrate the effects of lixisenatide on vascular complications and overall prognosis of patients with type 2 diabetes. [less ▲]

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See detailLa vignette diagnostique de l'etudiant. Diagnostic et evaluation d'une hypoglycemie chez le patient diabetique.
Scheen, André ULg

in Revue medicale de Liege (2014), 69(2), 110-5

Hypoglycaemic episodes are rather common among diabetic patients, especially those treated with sulfonylureas or insulin (more in type 1 than in type 2 diabetes). The presentation of hypoglycaemia may ... [more ▼]

Hypoglycaemic episodes are rather common among diabetic patients, especially those treated with sulfonylureas or insulin (more in type 1 than in type 2 diabetes). The presentation of hypoglycaemia may considerably vary from patient-to-patient and from time-to-time in a given patient. With the illustration of a clinical case, we will describe the characteristics of the three main types of hypoglycaemia: severe hypoglycaemia (with or without coma), symptomatic hypoglycaemia (with or without confirmation) and asymptomatic hypoglycaemia ("hypoglycaemia unawareness") discovered as a low blood glucose measurement. We will also briefly analyse the reasons of such differences and the potential clinical consequences that these three main types of hypoglycaemia may exert in the real life of diabetic patients. [less ▲]

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See detailEffects of glucose-lowering agents on vascular outcomes in type 2 diabetes: A critical reappraisal.
Scheen, André ULg; Charbonnel, B.

in Diabetes & metabolism (2014)

Type 2 diabetes mellitus (T2DM) is strongly associated with cardiovascular complications, especially coronary artery disease. Numerous epidemiological studies have shown a close relationship between major ... [more ▼]

Type 2 diabetes mellitus (T2DM) is strongly associated with cardiovascular complications, especially coronary artery disease. Numerous epidemiological studies have shown a close relationship between major cardiovascular events and glycaemia, and several pathophysiological mechanisms have been described that explain how hyperglycaemia induces vascular damage. However, randomized controlled trials investigating either an intensive glucose-lowering strategy vs standard care or the addition of a new glucose-lowering agent vs a placebo have largely failed to demonstrate any clinical benefits in terms of cardiovascular morbidity or mortality. This lack of evidence has led some people to contest the clinical efficacy of lowering blood glucose in patients with T2DM, despite its positive effects on microvascular complications. This article analyzes the various reasons that might explain such discrepancies. There are still strong arguments in favour of targeting hyperglycaemia while avoiding other counterproductive effects, such as hypoglycaemia and weight gain, and of integrating the glucose-lowering approach within a global multi-risk strategy to reduce the burden of cardiovascular disease in T2DM. [less ▲]

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See detailPharmacokinetic and toxicological considerations for the treatment of diabetes in patients with liver disease.
Scheen, André ULg

in Expert opinion on drug metabolism & toxicology (2014)

Introduction: Patients with type 2 diabetes have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis and about one-third of cirrhotic patients ... [more ▼]

Introduction: Patients with type 2 diabetes have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis and about one-third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents may be a cause for concern in the case of hepatic impairment (HI). Areas covered: An extensive literature search was performed to analyze the influence of HI on the pharmacokinetics (PK) of glucose-lowering agents and the potential consequences for clinical practice as far as the efficacy/safety balance of their use in diabetic patients with CLD is concerned. Expert opinion: Almost no PK studies have been published regarding metformin, sulfonylureas, thiazolidinediones and alpha-glucosidase inhibitors in patients with HI. Only mild changes in PK of glinides, dipeptidyl peptidase-4 inhibitors and sodium glucose cotransporters type 2 inhibitors were observed in dedicated PK studies in patients with various degrees of HI, presumably without major clinical relevance although large clinical experience is lacking. Glucagon-like peptide-1 receptor agonists have a renal excretion rather than liver metabolism. Rare anecdotal case reports of hepatotoxicity have been described with various glucose-lowering agents contrasting with numerous reassuring data. Nevertheless, caution should be recommended, especially in patients with advanced cirrhosis, including with the use of metformin. [less ▲]

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See detailPersonalising metformin therapy: a clinician's perspective
SCHEEN, André ULg

in Lancet Diabetes & Endocrinology (2014)

If lifestyle changes are not effective for maintaining glycaemic control, metformin is recommended as the first glucose-lowering drug to use in a patient with type 2 diabetes, if the patient has no ... [more ▼]

If lifestyle changes are not effective for maintaining glycaemic control, metformin is recommended as the first glucose-lowering drug to use in a patient with type 2 diabetes, if the patient has no contraindications—eg, renal impairment or hypoxic disorders.1 However, the glucose-lowering response to metformin can vary greatly between patients, with some people responding poorly to this biguanide. Because of the well known therapeutic inertia with respect to pharmacological treatment of diabetes, insufficient glucose control might persist for a long time before any treatment adjustment is made in people who respond poorly to metformin monotherapy. [less ▲]

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See detailCombating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes
SCHEEN, André ULg; Van Gaal, Luc

in The Lancet Diabetes & Endocrinology (2014)

The increasing prevalence of obesity is contributing substantially to the ongoing epidemic of type 2 diabetes. Abdominal adiposity, a feature of ectopic fat syndrome, is associated with silent ... [more ▼]

The increasing prevalence of obesity is contributing substantially to the ongoing epidemic of type 2 diabetes. Abdominal adiposity, a feature of ectopic fat syndrome, is associated with silent inflammation, abnormal hormone secretion, and various metabolic disturbances that contribute to insulin resistance and insulin secretory defects, resulting in type 2 diabetes, and induce a toxic pattern that leads to cardiovascular disease, liver pathologies, and cancer. Despite the importance of weight control strategies in the prevention and management of type 2 diabetes, long-term results from lifestyle or drug interventions are generally disappointing. Furthermore, most of the classic glucose-lowering drugs have a side-effect of weight gain, which renders the management of most overweight or obese people with type 2 diabetes even more challenging. Many anti-obesity pharmacological drugs targeting central control of appetite were withdrawn from the market because of safety concerns. The gastrointestinal lipase inhibitor orlistat was the only anti-obesity drug available until the recent US, but not European, launch of phentermine–controlled-release topiramate and lorcaserin. Improved knowledge about bodyweight regulation opens new prospects for the potential use of peptides derived from the gut or the adipose tissue. Combination therapy will probably be necessary to avoid compensatory mechanisms and potentiate initial weight loss while avoiding weight regain. New glucose-lowering treatments, especially glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, offer advantages over traditional antidiabetic drugs by promoting weight loss while improving glucose control. In this Review, we explore the overlapping pathophysiology and also how various treatments can, alone or in combination, combat the dual burden of obesity and type 2 diabetes. [less ▲]

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See detailDrug-Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus.
Scheen, André ULg

in Clinical pharmacokinetics (2014)

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel ... [more ▼]

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions (DDIs) regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure [assessed by peak plasma concentrations (C max) and area under the concentration-time curve (AUC)] to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose-lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin. Some modest changes were not considered as clinically relevant. However, drugs that could specifically interfere with the metabolic pathways of SGLT2 inhibitors [rifampicin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase (UGT)] may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin. Potential DDIs in patients with type 2 diabetes receiving chronic treatment with an SGLT2 inhibitor deserve further attention, especially in individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment. [less ▲]

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