Pharmacokinetics of dipeptidylpeptidase-4 inhibitors.
in Diabetes, Obesity & Metabolism (2010), 12(8), 648-58
Type 2 diabetes (T2DM) is a complex disease combining defects in insulin secretion and insulin action. New compounds have been developed for improving glucose-induced insulin secretion and glucose control ... [more ▼]
Type 2 diabetes (T2DM) is a complex disease combining defects in insulin secretion and insulin action. New compounds have been developed for improving glucose-induced insulin secretion and glucose control, without inducing hypoglycaemia or weight gain. Dipeptidylpeptidase-4 (DPP-4) inhibitors are new oral glucose-lowering agents, so-called incretin enhancers, which may be used as monotherapy or in combination with other antidiabetic compounds. Sitagliptin, vildaglipin and saxagliptin are already on the market in many countries, either as single agents or in fixed-dose combined formulations with metformin. Other DPP-4 inhibitors, such as alogliptin and linagliptin, are currently in late phase of development. The present paper summarizes and compares the main pharmacokinetics (PK) properties, that is, absorption, distribution, metabolism and elimination, of these five DPP-4 inhibitors. Available data were obtained in clinical trials performed in healthy young male subjects, patients with T2DM, and patients with either renal insufficiency or hepatic impairment. PK characteristics were generally similar in young healthy subjects and in middle-aged overweight patients with diabetes. All together gliptins have a good oral bioavailability which is not significantly influenced by food intake. PK/pharmacodynamics characteristics, that is, sufficiently prolonged half-life and sustained DPP-4 enzyme inactivation, generally allow one single oral administration per day for the management of T2DM; the only exception is vildagliptin for which a twice-daily administration is recommended because of a shorter half-life. DPP-4 inhibitors are in general not substrates for cytochrome P450 (except saxagliptin that is metabolized via CYP 3A4/A5) and do not act as inducers or inhibitors of this system. Several metabolites have been documented but most of them are inactive; however, the main metabolite of saxagliptin also exerts a significant DPP-4 inhibition and is half as potent as the parent compound. Renal excretion is the most important elimination pathway, except for linagliptin whose metabolism in the liver appears to be predominant. PK properties of gliptins, combined with their good safety profile, explain why no dose adjustment is necessary in elderly patients or in patients with mild to moderate hepatic impairment. As far as patients with renal impairment are concerned, significant increases in drug exposure for sitagliptin and saxagliptin have been reported so that appropriate reductions in daily dosages are recommended according to estimated glomerular filtration rate. The PK characteristics of DPP-4 inhibitors suggest that these compounds are not exposed to a high risk of drug-drug interactions. However, the daily dose of saxagliptin should be reduced when coadministered with potent CYP 3A4 inhibitors. In conclusion, besides their pharmacodynamic properties leading to effective glucose-lowering effect without inducing hypoglycaemia or weight gain, DPP-4 inhibitors show favourable PK properties, which contribute to a good efficacy/safety ratio for the management of T2DM in clinical practice. [less ▲]Detailed reference viewed: 20 (0 ULg)
Aptitude physique versus adiposité : aspects physiopathologiques et impacts cardio-métaboliques chez le sujet adulte non diabétique
Esser, Nathalie ; Paquot, Nicolas ; Scheen, André
in Médecine des Maladies Métaboliques (2010), 4
L’excès de masse grasse (adiposité), surtout abdominale, induit des effets cardio-métaboliques néfastes, alors que l’exercice musculaire et une bonne aptitude physique exercent globalement une influence ... [more ▼]
L’excès de masse grasse (adiposité), surtout abdominale, induit des effets cardio-métaboliques néfastes, alors que l’exercice musculaire et une bonne aptitude physique exercent globalement une influence favorable. Les effets délétères d’un excès de masse grasse (fatness) pourraient donc être contrecarrés par la pratique régulière d’exercices aboutissant à une bonne forme physique (fitness). Cet article analyse d’abord les différents mécanismes physiopathologiques par lesquels l’exercice physique produit des effets bénéfiques chez la personne avec excès pondéral et fait le distinguo entre la pratique d’une activité physique (exercice musculaire) stricto sensu et aptitude physique (fitness). Ensuite, il décrit les études les plus importantes ayant analysé les relations entre le niveau d’aptitude physique et le degré d’adiposité chez le sujet adulte en surpoids ou obèse non diabétique et leurs influences respectives sur le risque de survenue de troubles métaboliques (syndrome métabolique) et sur la mortalité, en particulier cardiovasculaire. [less ▲]Detailed reference viewed: 78 (2 ULg)
Cardiovascular risk-benefit profile of sibutramine.
in American Journal of Cardiovascular Drugs : Drugs, Devices, & Other Interventions (2010), 10(5), 321-34
Sibutramine is a combined norepinephrine and serotonin reuptake inhibitor used as an antiobesity agent to reduce appetite and promote weight loss in combination with diet and exercise. At a daily dose of ... [more ▼]
Sibutramine is a combined norepinephrine and serotonin reuptake inhibitor used as an antiobesity agent to reduce appetite and promote weight loss in combination with diet and exercise. At a daily dose of 10-20 mg, it was initially considered to have a good safety profile, as it does not induce primary pulmonary hypertension or adverse effects on cardiac valves, in contrast to previous reports relating to some other antiobesity agents. However, it exerts disparate effects on cardiovascular risk factors. On the one hand, sibutramine may have antiatherogenic activities, as it improves insulin resistance, glucose metabolism, dyslipidemia, and inflammatory markers, with most of these effects resulting from weight loss rather than from an intrinsic effect of the drug. On the other hand, because of its specific mode of action, sibutramine exerts a peripheral sympathomimetic effect, which induces a moderate increase in heart rate and attenuates the reduction in BP attributable to weight loss or even slightly increases BP. It may also prolong the QT interval, an effect that could induce arrhythmias. Because of these complex effects, it is difficult to conclude what the final impact of sibutramine on cardiovascular outcomes might be. Sibutramine has been shown to exert favorable effects on some surrogate cardiovascular endpoints such as reduction of left ventricular hypertrophy and improvement of endothelial dysfunction. A good cardiovascular safety profile was demonstrated in numerous 1- to 2-year controlled trials, in both diabetic and nondiabetic well selected patients, as well as in several observational studies. However, since 2002, several cardiovascular adverse events (hypertension, tachycardia, arrhythmias, and myocardial infarction) have been reported in sibutramine-treated patients. This led to a contraindication of the use of this antiobesity agent in patients with established coronary heart disease, previous stroke, heart failure, or cardiac arrhythmias. SCOUT (Sibutramine Cardiovascular and Diabetes Outcome Study) was designed to prospectively evaluate the efficacy/safety ratio of sibutramine in a high-risk population. The efficacy/safety results of the first 6-week lead-in open period of treatment with sibutramine 10 mg/day were reassuring in 10 742 overweight/obese high-risk subjects (97% had cardiovascular disease, 88% had hypertension, and 84% had type 2 diabetes mellitus). However, the final results of SCOUT showed that long-term (5 years') treatment with sibutramine (10-15 mg/day) exposed subjects with pre-existing cardiovascular disease to a significantly increased risk for nonfatal myocardial infarction and nonfatal stroke, but not cardiovascular death or all-cause mortality. Because the benefit of sibutramine as a weight-loss aid seems not to outweigh the cardiovascular risks, the European Medicines Agency recommended the suspension of marketing authorizations for sibutramine across the EU. The US FDA stated that the drug should carry a 'black box' warning due to an increased risk of stroke and heart attack in patients with a history of cardiovascular disease. In conclusion, concern still persists about the safety profile of sibutramine regarding cardiovascular outcomes, and the drug should not be prescribed for overweight/obese patients with a high cardiovascular risk profile. [less ▲]Detailed reference viewed: 27 (1 ULg)
Pharmacokinetic and pharmacodynamic evaluation of sitagliptin plus metformin.
in Expert Opinion on Drug Metabolism & Toxicology (2010), 6(10), 1265-76
IMPORTANCE OF THE FIELD: Type 2 diabetes is an increasingly prevalent disease resulting from various complex combinations of defects in insulin secretion and insulin action. Adequate blood glucose control ... [more ▼]
IMPORTANCE OF THE FIELD: Type 2 diabetes is an increasingly prevalent disease resulting from various complex combinations of defects in insulin secretion and insulin action. Adequate blood glucose control is necessary to minimize complications. DPP IV inhibitors (sitagliptin, vildagliptin, saxagliptin) offer new options for combined pharmacological therapy. AREAS COVERED IN THIS REVIEW: An extensive literature search was performed to analyze the potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between metformin (first-line drug for the management of type 2 diabetes) and sitagliptin (first commercialized DPP IV inhibitor). Metformin and sitagliptin may be administered together, either separately or in fixed-dose combination. WHAT THE READER WILL GAIN: Updated information about PK/PD data on metformin alone, sitagliptin alone and sitagliptin plus metformin. Metformin and sitagliptin are not prone to PK drug-drug interactions. Their co-administration, either separately or in a fixed-dose combination, improves blood glucose control more potently than either compound separately, without hypoglycemia and without increasing metformin-related gastrointestinal side effects. TAKE HOME MESSAGE: The combination sitagliptin plus metformin may be used as a first- or second-line therapy in the management of type 2 diabetes. [less ▲]Detailed reference viewed: 43 (2 ULg)
L’hyperglycémie provoquée par voie orale (HGPO) revisitée 1re partie : Tolérance au glucose, diabète gestationnel et hypoglycémie réactive
Scheen, André ; Luyckx, Françoise
in Médecine des Maladies Métaboliques (2010), 4(5), 569-574
Oral glucose tolerance test (OGTT) has been widely used for the diagnosis of diabetes mellitus, gestational diabetes, impaired glucose tolerance or reactive hypoglycemia. Since almost 10 years, however ... [more ▼]
Oral glucose tolerance test (OGTT) has been widely used for the diagnosis of diabetes mellitus, gestational diabetes, impaired glucose tolerance or reactive hypoglycemia. Since almost 10 years, however, it has been proposed to limit the use of this dynamic test, favoring instead the measurement of either fasting plasma glucose or glycated hemoglobin. Nevertheless, almost all recent important studies used OGTT as reference test. In this first article, we will consider the potential interest of OGTT as diagnostic or prognostic test able to evaluate glucose regulation. In a second article, we will describe how to use OGTT to derive indices that quantitatively evaluate insulin secretion and/or insulin sensitivity. [less ▲]Detailed reference viewed: 202 (4 ULg)
Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial
; Scheen, André
in Lancet (2010), 376
BACKGROUND: Blockade of the endocannabinoid receptor reduces obesity and improves metabolic abnormalities such as triglycerides, HDL cholesterol, and fasting blood glucose. We assessed whether rimonabant ... [more ▼]
BACKGROUND: Blockade of the endocannabinoid receptor reduces obesity and improves metabolic abnormalities such as triglycerides, HDL cholesterol, and fasting blood glucose. We assessed whether rimonabant would improve major vascular event-free survival. METHODS: This double-blind, placebo-controlled trial was undertaken in 974 hospitals in 42 countries. 18,695 patients with previously manifest or increased risk of vascular disease were randomly assigned to receive either rimonabant 20 mg (n=9381) or matching placebo (n=9314). Randomisation was stratified by centre, implemented with an independent interactive voice response system, and all study personnel and participants were masked to group assignment. The primary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke, as determined via central adjudication. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00263042. FINDINGS: At a mean follow-up of 13.8 months (95% CI 13.6-14.0), the trial was prematurely discontinued because of concerns by health regulatory authorities in three countries about suicide in individuals receiving rimonabant. All randomised participants were analysed. At the close of the trial (Nov 6, 2008), the composite primary endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 364 (3.9%) patients assigned to rimonabant and 375 (4.0%) assigned to placebo (hazard ratio 0.97, 95% CI 0.84-1.12, p=0.68). With rimonabant, gastrointestinal (3038 [33%] vs 2084 [22%]), neuropsychiatric (3028 [32%] vs 1989 [21%]), and serious psychiatric side-effects (232 [2.5%] vs 120 [1.3%]) were significantly increased compared with placebo. Four patients in the rimonabant group and one in the placebo group committed suicide. INTERPRETATION: The premature termination of this trial has important lessons for drug development. A drug that was being marketed for weight loss, but being tested for improving cardiovascular outcomes, induced a level of serious neuropsychiatric effects that was deemed unacceptable by regulatory authorities, and both the drug and the trial were abruptly terminated. [less ▲]Detailed reference viewed: 12 (1 ULg)
A propos de l'inertie et de la non-observance therapeutiques.
in Revue Médicale Suisse (2010), 6(260), 1571-2Detailed reference viewed: 22 (1 ULg)
Le medicament du mois. Liraglutide (Victoza): analogue du glucagon-like- peptide-1 humain en une injection par jour pour le traitement du diabete de type 2.
Scheen, André ;
in Revue Médicale de Liège (2010), 65(7-8), 464-70
Liraglutide (Victoza) is a peptide produced by DNA recombinant technology, which presents 97% homology with human glucagon-like peptide-1 (GLP-1) but is resistant to dipeptidylpeptidase-4, the enzyme that ... [more ▼]
Liraglutide (Victoza) is a peptide produced by DNA recombinant technology, which presents 97% homology with human glucagon-like peptide-1 (GLP-1) but is resistant to dipeptidylpeptidase-4, the enzyme that degrades the natural hormone. It actives the GLP-1 receptor and exerts an incretin mimetic effect during at least 24 hours after a single subcutaneous injection. Besides a glucose-dependent stimulatory effect of insulin secretion, liraglutide inhibits glucagon secretion and retards gastric emptying. In patients with type 2 diabetes, it reduces glycated haemoglobin by at least 1%, without inducing hypoglycaemia. It also induces a moderate weight loss and a mild reduction in blood pressure. Gastrointestinal adverse events (nausea, vomiting) may occur during the initial phase of treatment, but rarely impose the interruption of the medication and usually diminish with time.Although indicated in combination with other glucose-lowering agents, liraglutide is currently reimbursed in Belgium only if administered in patients with type 2 diabetes not sufficiently controlled with a combination of metformin plus sulfonylurea or metformin plus a thiazolidinedione. Victoza is presented in prefilled pens and is injected subcutaneously once a day. Treatment will be initiated with 0.6 mg to improve digestive tolerance and the daily dose will be increased to 1.2 mg (usual dose) after at least one week, and up to 1.8 mg (maximal dose) if necessary. [less ▲]Detailed reference viewed: 132 (0 ULg)
Patient coronarien avec co-morbidites: integrer indications et contre-indications dans le raisonnement pharmaco-therapeutique.
in Revue Médicale de Liège (2010), 65(7-8), 476-81
A patient with abdominal obesity, type 2 diabetes, arterial hypertension and dyslipidaemia is exposed to a high risk of coronary artery disease, congestive heart failure and/or renal insufficiency. The ... [more ▼]
A patient with abdominal obesity, type 2 diabetes, arterial hypertension and dyslipidaemia is exposed to a high risk of coronary artery disease, congestive heart failure and/or renal insufficiency. The management of such a patient requires different medications, which should be prescribed by taking into account both (relative and absolute) indications and contra-indications to improve overall prognosis. The present clinical case report illustrates the therapeutic reasoning leading to an appropriate pharmacological polytherapy, combined with life-style changes. [less ▲]Detailed reference viewed: 22 (0 ULg)
Le medicament du mois. Saxagliptine (ONGLYZA): nouvel inhibiteur de la dipeptidylpeptidase-4 pour le traitement oral du diabete de type 2.
in Revue Médicale de Liège (2010), 65(9), 527-32
Saxagliptin (Onglyza) is a specific and reversible inhibitor of dipeptidylpeptidase-4 (DPP-4), which inhibits the activity of the enzyme for at least 24 hours after one single oral administration. It ... [more ▼]
Saxagliptin (Onglyza) is a specific and reversible inhibitor of dipeptidylpeptidase-4 (DPP-4), which inhibits the activity of the enzyme for at least 24 hours after one single oral administration. It increases the circulating levels of incretin hormones (GLP-1, GIP), which contributes to amplify the insulin secretory response to meals and to reduce postprandial hyperglycaemia and, subsequently, fasting glycaemia. Saxagliptin, 5 mg once daily, has been shown to be effective in patients with type 2 diabetes treated with diet alone, metformin, sulfonylurea or glitazone, with a favourable tolerance profile. Reduction in glycated haemoglobin (HbA(1c)) averaged 0.6-0.8%, without increasing the risk of hypoglycaemia or promoting weight gain. The only indication of saxagliptin that is currently reimbursed in Belgium is the treatment of patients not controlled with metformin, the oral antidiabetic agent that is recommended as first line therapy in the management of type 2 diabetes. [less ▲]Detailed reference viewed: 65 (2 ULg)
Le medicament du moi. Dabigatran etexilate (Pradaxa): anticoagulant oral, inhibiteur direct selectif de la thrombine
Lancellotti, Patrizio ; Scheen, André
in Revue Médicale de Liège (2010), 65(10), 588-92
Dabigatran (Pradaxa) is a new oral, direct, selective and reversible thrombin inhibitor (factor IIa) acting as anticoagulant. Pradaxa does not require monitoring or dose adjustment, except in cases of ... [more ▼]
Dabigatran (Pradaxa) is a new oral, direct, selective and reversible thrombin inhibitor (factor IIa) acting as anticoagulant. Pradaxa does not require monitoring or dose adjustment, except in cases of moderate renal insufficiency or in elderly patients (>75 years old). It is currently indicated for prophylaxis against venous thromboembolism after total hip or knee replacement surgery. Pradaxa has been shown to be as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip or knee replacement surgery, with a similar safety profile. The recommended dose of 220 mg is administered once-daily, starting with a half-dose 1-4 h after surgery. The total duration of treatment is 10 days for knee surgery and 28-35 days in case of hip replacement. Contrary to enoxaparin, with Pradaxa there is no risk of drug-related thrombocytopenia. Of note, this promising new anticoagulant has also shown to be more effective than warfarin for stroke prevention in patients with non-valvular atrial fibrillation and as effective as warfarin for the treatment of acute venous thromboembolism (indications not recognized yet). [less ▲]Detailed reference viewed: 120 (0 ULg)
Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus.
Scheen, André ; ; et al
in Diabetes/Metabolism Research & Reviews (2010), 26(7), 540-9
BACKGROUND: Dipeptidyl peptidase-4 inhibitors improve glycaemic control in patients with type 2 diabetes mellitus when used as monotherapy or in combination with other anti-diabetic drugs (metformin ... [more ▼]
BACKGROUND: Dipeptidyl peptidase-4 inhibitors improve glycaemic control in patients with type 2 diabetes mellitus when used as monotherapy or in combination with other anti-diabetic drugs (metformin, sulphonylurea, or thiazolidinedione). This 18-week, phase 3b, multicentre, double-blind, noninferiority trial compared the efficacy and safety of two dipeptidyl peptidase-4 inhibitors, saxagliptin and sitagliptin, in patients whose glycaemia was inadequately controlled with metformin. METHODS: Adult type 2 diabetes mellitus patients (N = 801) with glycated haemoglobin (HbA(1c)) 6.5-10% on stable metformin doses (1500-3000 mg/day) were randomized 1 : 1 to add-on 5 mg saxagliptin or 100 mg sitagliptin once daily for 18 weeks. The primary efficacy analysis was a comparison of the change from baseline HbA(1c) at week 18 in per-protocol patients. Noninferiority was concluded if the upper limit of the two-sided 95% confidence interval of the HbA(1c) difference between treatments was < 0.3%. RESULTS: The adjusted mean changes in HbA(1c) following the addition of saxagliptin or sitagliptin to stable metformin therapy were - 0.52 and - 0.62%, respectively. The between-group difference was 0.09% (95% confidence interval, - 0.01 to 0.20%), demonstrating noninferiority. Both treatments were generally well tolerated; incidence and types of adverse events were comparable between groups. Hypoglycaemic events, mostly mild, were reported in approximately 3% of patients in each treatment group. Body weight declined by a mean of 0.4 kg in both groups. CONCLUSIONS: Saxagliptin added to metformin therapy was effective in improving glycaemic control in patients with type 2 diabetes mellitus inadequately controlled by metformin alone; saxagliptin plus metformin was noninferior to sitagliptin plus metformin, and was generally well tolerated. [less ▲]Detailed reference viewed: 26 (1 ULg)
Education therapeutique et mesure continue de la glycemie chez le patient diabetique insulino-traite.
Thielen, Vinciane ; Radermecker, Régis ; et al
in Revue Médicale Suisse (2010), 6(260), 1596-600
L’efficacité d’un programme éducationnel fondé sur l’utilisation d’une mesure continue du glucose avec un affichage en temps réel a été évaluée chez des patients diabétiques de type 1 (système couplé à ... [more ▼]
L’efficacité d’un programme éducationnel fondé sur l’utilisation d’une mesure continue du glucose avec un affichage en temps réel a été évaluée chez des patients diabétiques de type 1 (système couplé à une pompe à insuline externe - Paradigm Real Time®) et chez des patients diabétiques de type 2 mal contrôlés sous insuline (système Guardian RT® une semaine par mois pendant 3 mois versus automesure classique). Ces deux essais pilote montrent une diminution du taux d’hémoglobine glyquée (HbA1c) avec le « glucose sensor », avec moins d’hypoglycémies symptomatiques. Malgré certaines difficultés techniques (surtout chez les diabétiques de type 2), l’approche représente un outil intéressant d’éducation thérapeutique. Ces résultats prometteurs plaident pour des études de plus grande envergure chez des patients diabétiques bien sélectionnés. [less ▲]Detailed reference viewed: 44 (2 ULg)
Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis.
; ; et al
in Diabetologia (2010)
The ADA and the EASD recently published a consensus statement for the medical management of hyperglycaemia in patients with type 2 diabetes. The authors advocate initial treatment with metformin ... [more ▼]
The ADA and the EASD recently published a consensus statement for the medical management of hyperglycaemia in patients with type 2 diabetes. The authors advocate initial treatment with metformin monotherapy and lifestyle modification, followed by addition of basal insulin or a sulfonylurea if glycaemic goals are not met (tier 1 recommendations). All other glucose-lowering therapies are relegated to a secondary (tier 2) status and only recommended for selected clinical settings. In our view, this algorithm does not offer physicians and patients the appropriate selection of options to individualise and optimise care with a view to sustained control of blood glucose and reduction both of diabetes complications and cardiovascular risk. This paper critically assesses the basis of the ADA/EASD algorithm and the resulting tiers of treatment options. [less ▲]Detailed reference viewed: 36 (1 ULg)
Pioglitazone Use in Combination with Insulin in the Prospective Pioglitazone Clinical Trial in Macrovascular Events Study (PROactive19).
; ; et al
in Journal of Clinical Endocrinology and Metabolism (2010)
Objective: In this post hoc analysis, we examined insulin requirements and regimens, glycemic control, cardiovascular outcomes, and safety in the patients treated with insulin at baseline in the ... [more ▼]
Objective: In this post hoc analysis, we examined insulin requirements and regimens, glycemic control, cardiovascular outcomes, and safety in the patients treated with insulin at baseline in the Prospective Pioglitazone Clinical Trial in Macrovascular Events study. Design: The Prospective Pioglitazone Clinical Trial in Macrovascular Events study was a double-blind, placebo-controlled outcome study (mean follow-up 34.5 months) in 5238 high-risk patients with type 2 diabetes randomized to pioglitazone (force titrated to 45 mg) or placebo. One third of the total population (pioglitazone 864; placebo 896) were receiving insulin at baseline. Results: A rapid and sustained decrease in insulin dose was observed with pioglitazone vs. a progressive increase with placebo. By study end, the mean insulin dose was lower with pioglitazone (42 vs. 55 U/d with placebo; P < 0.0001). The insulin regimen (number on insulin, need for multiple injections, and reduction in oral agents) had been simplified vs. placebo; nevertheless, a greater glycosylated hemoglobin reduction was observed with pioglitazone (-0.93%) vs. placebo (-0.45%; P < 0.0001). At the final visit, insulin had been discontinued in 9% of pioglitazone vs. 2% of placebo patients (P < 0.0001). More insulin-resistant patients (defined as poorly controlled type 2 diabetes despite high doses of insulin) in the pioglitazone plus insulin group showed the greatest glycosylated hemoglobin decline. There were nonsignificant reductions with pioglitazone relative to placebo in the cardiovascular primary (hazard ratio 0.86; 95% confidence interval 0.71, 1.04; P = 0.1198) and main secondary (hazard ratio 0.85; 95% confidence interval 0.67, 1.08; P = 0.1831) end points in insulin-treated patients. The rates of overall heart failure, edema, and hypoglycemia were higher with pioglitazone [13.5 vs 10.5% (P = 0.0489); 30.8 vs. 18.2% (P < 0.0001); and 42.1 vs 29.0% (P < 0.0001), respectively], but there were no significant differences in serious events. Conclusions: Pioglitazone use in combination with insulin resulted in a sustained improved glycemic control and allowed the treatment regimens to be simplified and the insulin doses reduced. [less ▲]Detailed reference viewed: 11 (0 ULg)
Education on sensor-augmented pump use improves glucose control in type-1 diabetic patients.
Thielen, Vinciane ; ; et al
in Diabètes & Métabolism (2010)Detailed reference viewed: 34 (1 ULg)
La vignette diagnostique de l'etudiant: apprentissage au raisonnement diagnostique.
Moonen, Gustave ; Scheen, André
in Revue Médicale de Liège (2010), 65(1), 46-8Detailed reference viewed: 22 (7 ULg)
Aptitude physique versus adiposité : impacts cardio-métaboliques respectifs chez l’enfant/adolescent et chez la personne âgée
Esser, Nathalie ; Paquot, Nicolas ; Scheen, André
in Médecine des Maladies Métaboliques (2010), 4
Le sujet adulte d’âge moyen en surpoids ou obèse est caractérisé par une adiposité exagérée, généralement combinée à une aptitude physique cardio-respiratoire déficiente. La pratique régulière d’une ... [more ▼]
Le sujet adulte d’âge moyen en surpoids ou obèse est caractérisé par une adiposité exagérée, généralement combinée à une aptitude physique cardio-respiratoire déficiente. La pratique régulière d’une activité physique d’endurance améliore le profil de risque cardio-métabolique dans cette tranche d’âge. Le manque d’activité physique chez les adolescents contribue à augmenter leur masse grasse et à induire des anomalies métaboliques, tandis que la sédentarité marquée des sujets âgés peut conduire à un excès de graisse combiné à une fonte musculaire (obésité sarcopénique). Dans ces deux tranches d’âge, les effets néfastes d’un excès de masse grasse (fatness) pourraient être contrecarrés, voire annulés, par la pratique régulière d’exercices musculaires conduisant à une meilleure aptitude physique (fitness). Cet article décrit les relations entre fitness et fatness, et les impacts cardio-métaboliques respectifs de ces deux composantes, d’une part, dans la population jeune (< 20 ans), d’autre part dans la population âgée (> 60 ans). [less ▲]Detailed reference viewed: 83 (4 ULg)
Strategies pour eviter l'inertie et la non-observance dans les essais cliniques.
Jandrain, Bernard ; Ernest, Philippe ; Radermecker, Régis et al
in Revue Médicale de Liège (2010), 65(5-6), 246-9
Randomised controlled trials play a key role in evidence-based medicine as far as the assessment of both efficacy and safety of drugs is concerned. Various strategies are used to avoid physician's inertia ... [more ▼]
Randomised controlled trials play a key role in evidence-based medicine as far as the assessment of both efficacy and safety of drugs is concerned. Various strategies are used to avoid physician's inertia and to combat patient's non compliance, two pitfalls that may hinder the demonstration of the therapeutic efficacy of the drug. Clinical inertia may be limited by titration, forced or optional, driven by therapeutic targets, or by the use, if necessary, of rescue medications. Compliance may be verified by "pill count". This simple technique allows to exclude non compliant patients when they are detected during the placebo run-in period before randomisation or not to take into account patients with poor compliance in the final evaluation by using a statistical analysis restricted to individuals who have strictly adhered to the study protocol ("per protocol analysis"). Self-monitoring and patient's empowerment in the treatment also contribute to improve drug compliance. Clinicians may take advantage of these approaches derived from clinical trials to improve their daily practice. [less ▲]Detailed reference viewed: 85 (6 ULg)