A review of gliptins in 2011.
in Expert Opinion on Pharmacotherapy (2012), 13(1), 81-99
INTRODUCTION: Dipeptidylpeptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes (T2DM). AREAS COVERED: This paper is an updated review, providing an analysis of both the ... [more ▼]
INTRODUCTION: Dipeptidylpeptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes (T2DM). AREAS COVERED: This paper is an updated review, providing an analysis of both the similarities and the differences between the various compounds known as gliptins, currently used in the clinic (sitagliptin, vildagliptin, saxagliptin, alogliptin and linagliptin). This paper discusses the pharmacokinetic and pharmacodynamic characteristics of gliptins; both the efficacy and safety profiles of gliptins in clinical trials (compared with classical glucose-lowering agents), given as monotherapy or in combination, including in special populations; the positioning of DPP-4 inhibitors in the management of T2DM in recent guidelines; and various unanswered questions and perspectives. EXPERT OPINION: The role of DPP-4 inhibitors in the therapeutic armamentarium of T2DM is evolving, as their potential strengths and weaknesses become better defined. Future critical issues may include the durability of glucose control, resulting from better beta-cell protection, positive effects on cardiovascular outcomes and long-term safety issues. [less ▲]Detailed reference viewed: 42 (2 ULg)
Saxagliptin plus metformin combination in patients with type 2 diabetes and renal impairment.
in Expert Opinion on Drug Metabolism & Toxicology (2012), 8(3), 383-94
INTRODUCTION: A metformin plus saxagliptin fixed-dose combination is now proposed to clinicians. Furthermore, saxagliptin's license was recently extended to include diabetic patients with moderate or ... [more ▼]
INTRODUCTION: A metformin plus saxagliptin fixed-dose combination is now proposed to clinicians. Furthermore, saxagliptin's license was recently extended to include diabetic patients with moderate or severe renal impairment (RI). However, metformin is still contraindicated in patients with RI. AREAS COVERED: This review analyses the pro and contra of using a combination of saxagliptin and metformin (separately or as a fixed-dose combination) in type 2 diabetic patients with moderate or severe RI. An extensive literature search of all pharmacokinetic data and efficacy/safety profile of metformin and saxagliptin in subjects with RI was performed. EXPERT OPINION: Since both metformin and saxagliptin are excreted via the kidney, dose adjustment is required in case of moderate-to-severe RI (half dose of saxagliptin). However, major discrepancies exist between guidelines (metformin excluded in case of RI because of the risk of lactic acidosis) and real life (metformin widely prescribed in patients with some degree of RI). Physicians should weigh the benefit/risk ratio carefully before deciding to prescribe or withdraw the combination metformin plus saxagliptin in patients with stable RI. A redefinition of contraindications to metformin will enable more physicians to prescribe within guidelines and to administer saxagliptin combined with metformin in more patients who clearly may benefit from this combination. [less ▲]Detailed reference viewed: 25 (2 ULg)
Differential effects of olanzapine and risperidone on plasma adiponectin levels over time: Results from a 3-month prospective open-label study.
; ; et al
in European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology (2012), 22
Second-generation antipsychotics (SGA), especially clozapine and olanzapine, are associated with an increased metabolic risk. Recent research showed that plasma adiponectin levels, an adipocyte-derived ... [more ▼]
Second-generation antipsychotics (SGA), especially clozapine and olanzapine, are associated with an increased metabolic risk. Recent research showed that plasma adiponectin levels, an adipocyte-derived hormone that increases insulin sensitivity, vary in the same way in schizophrenic patients as in the general population according to gender, adiposity and metabolic syndrome (MetS). The aim of the present study was to investigate whether different SGAs differentially affect plasma adiponectin levels independent of body mass index (BMI) and MetS status. 113 patients with schizophrenia (65.5% males, 32.3years old) who were free of antipsychotic medication were enrolled in this open-label prospective single-center study and received either risperidone (n=54) or olanzapine (n=59). They were followed prospectively for 12weeks. Average daily dose was 4.4mg/day for risperidone and 17.4mg/day for olanzapine. Plasma adiponectin levels as well as fasting metabolic parameters were measured at baseline, 6weeks and 12weeks. The two groups had similar baseline demographic and metabolic characteristics. A significant increase in body weight was observed over time. This increase was significantly larger in the olanzapine group than in the risperidone group (+7.0kg versus +3.1kg, p<0.0002). Changes in fasting glucose and insulin levels and in HOMA-IR, an index of insulin resistance, were not significantly different in both treatment groups. MetS prevalence increased significantly more in the olanzapine group as compared to the risperidone groups where the prevalence did not change over time. We observed a significant (p=0.0015) treatment by time interaction showing an adiponectin increase in the risperidone-treated patients (from 10,154 to 11,124ng/ml) whereas adiponectin levels decreased in olanzapine treated patients (from 11,280 to 8988ng/ml). This effect was independent of BMI and the presence/absence of MetS. The differential effect of antipsychotic treatment (risperidone versus olanzapine) on plasma adiponectin levels over time, independent of changes in waist circumference and antipsychotic dosing, suggests a specific effect on adipose tissues, similar to what has been observed in animal models. The observed olanzapine-associated reduction in plasma adiponectin levels may at least partially contribute to the increased metabolic risk of olanzapine compared to risperidone. [less ▲]Detailed reference viewed: 54 (6 ULg)
Inhibiteurs du cotransporteur du glucose SGLT rénal pour traiter le diabète de type 2
SCHEEN, André ; RADERMECKER, Régis ; ERNEST, Philippe et al
in Revue Médicale Suisse (2011), 7(306), 1621-1629Detailed reference viewed: 27 (6 ULg)
Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes
; ; et al
in New England Journal of Medicine [=NEJM] (2011), 364
BACKGROUND: Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease. We investigated whether treatment with an angiotensin-receptor blocker (ARB) would delay or ... [more ▼]
BACKGROUND: Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease. We investigated whether treatment with an angiotensin-receptor blocker (ARB) would delay or prevent the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria. METHODS: In a randomized, double-blind, multicenter, controlled trial, we assigned 4447 patients with type 2 diabetes to receive olmesartan (at a dose of 40 mg once daily) or placebo for a median of 3.2 years. Additional antihypertensive drugs (except angiotensin-converting-enzyme inhibitors or ARBs) were used as needed to lower blood pressure to less than 130/80 mm Hg. The primary outcome was the time to the first onset of microalbuminuria. The times to the onset of renal and cardiovascular events were analyzed as secondary end points. RESULTS: The target blood pressure (<130/80 mm Hg) was achieved in nearly 80% of the patients taking olmesartan and 71% taking placebo; blood pressure measured in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group. Microalbuminuria developed in 8.2% of the patients in the olmesartan group (178 of 2160 patients who could be evaluated) and 9.8% in the placebo group (210 of 2139); the time to the onset of microalbuminuria was increased by 23% with olmesartan (hazard ratio for onset of microalbuminuria, 0.77; 95% confidence interval, 0.63 to 0.94; P=0.01). The serum creatinine level doubled in 1% of the patients in each group. Slightly fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events--81 of 2232 patients (3.6%) as compared with 91 of 2215 patients (4.1%) (P=0.37)--but a greater number had fatal cardiovascular events--15 patients (0.7%) as compared with 3 patients (0.1%) (P=0.01), a difference that was attributable in part to a higher rate of death from cardiovascular causes in the olmesartan group than in the placebo group among patients with preexisting coronary heart disease (11 of 564 patients [2.0%] vs. 1 of 540 [0.2%], P=0.02). CONCLUSIONS: Olmesartan was associated with a delayed onset of microalbuminuria, even though blood-pressure control in both groups was excellent according to current standards. The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern. (Funded by Daiichi Sankyo; ClinicalTrials.gov number, NCT00185159.). [less ▲]Detailed reference viewed: 33 (5 ULg)
Hypocortisolism induces chronic respiratory failure
PIRLET, Charles ; BECK, Emmanuel ; SCHEEN, André et al
in Respiratory Medicine (2011), 4(3), 107-108
Hypocortisolism is an uncommon condition. Its association with myopathy and respiratoryfailure has only rarely been described. We report the case of a 52 year-old woman presenting with progressive ... [more ▼]
Hypocortisolism is an uncommon condition. Its association with myopathy and respiratoryfailure has only rarely been described. We report the case of a 52 year-old woman presenting with progressive dyspnoea. Work-up revealed a severe restrictive syndrome with hypoxaemia. Further investigations showed hypocortisolism of pituitary origin. Response to hydrocortisone allowed us to conclude to an unusual case of hypocortisolic myopathy affecting the respiratory muscles. [less ▲]Detailed reference viewed: 39 (3 ULg)
Prevalence of the metabolic syndrome in Luxembourg according to the Joint Interim Statement definition estimated from the ORISCAV-LUX study
; Donneau, Anne-Françoise ; et al
Poster (2011)Detailed reference viewed: 23 (5 ULg)
Prevalence of the metabolic syndrome in Luxembourg according to the Joint Interim Statement definition estimated from the ORISCAV-LUX study.
; Donneau, Anne-Françoise ; et al
in BMC Public Health (2011), 11(1), 4
ABSTRACT: BACKGROUND: The prevalence of the metabolic syndrome (MS) has been determined in many countries worldwide but never in Luxembourg. This research aimed to 1) establish the gender- and age ... [more ▼]
ABSTRACT: BACKGROUND: The prevalence of the metabolic syndrome (MS) has been determined in many countries worldwide but never in Luxembourg. This research aimed to 1) establish the gender- and age-specific prevalence of MS and its components in the general adult population of Luxembourg, according to the most recent Joint Interim Statement (JIS) definition, by using both the high and low cut-off points to define abdominal obesity, and 2) compare and assess the degree of agreement with the Revised National Cholesterol Education Programme-Adult Treatment Panel III (R-ATPIII) and the International Diabetes Federation (IDF) definitions. METHODS: A representative stratified random sample of 1349 European subjects, aged 18-69 years, participated to ORISCAV-LUX survey. Logistic regression and odds ratios (OR) were used to study MS prevalence with respect to gender and age. The Framingham risk score (FRS) to predict the 10-year coronary heart disease (CHD) risk was calculated to compare the proportion of MS cases below or above 20%, according to both high and low waist circumference (WC) thresholds. Cohen's kappa coefficient (kappa) was utilized to measure the degree of agreement between MS definitions. RESULTS: The prevalence of the MS defined by the JIS was 28.0% and 24.7% when using the low (94/80) and the high (102/88) WC cut-off points, respectively. The prevalence was significantly higher in men than in women (OR = 2.6 and 2.3 for the low and high WC thresholds), as were all components of the MS except abdominal obesity measured by both thresholds. It also increased with age (OR values in age categories ranging from 2.7 to 28 when compared to the younger subjects for low WC and from 3.3 to 31 for the high WC cut-offs). The 10-year predicted risk of CHD by FRS did not depend on the threshold used. Globally, excellent agreement was observed between the three definitions of MS (kappa= 0.89), in particular between JIS and IDF (kappa = 0.93). Agreement was significantly higher in women than in men, and differed between age groups. CONCLUSION: Regardless of the definition used, the adult population of Luxembourg reveals a high MS prevalence. Our findings contribute to build evidence regarding the definitive construct of the MS, to help selecting the waist circumference thresholds for Europid populations, and to support the need to revise the guidelines for abdominal obesity levels. [less ▲]Detailed reference viewed: 69 (19 ULg)
DPP-4 inhibitors in the management of type 2 diabetes: A critical review of head-to-head trials.
in Diabètes & Métabolism (2011)
Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that ... [more ▼]
Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that DPP-4 inhibitors exert slightly less pronounced HbA(1c) reduction than metformin (with the advantage of better gastrointestinal tolerability) and similar glucose-lowering effects as with a thiazolidinedione (TZD; with the advantage of no weight gain). In metformin-treated patients, gliptins were associated with similar HbA(1c) reductions compared with a sulphonylurea (SU; with the advantage of no weight gain, considerably fewer hypoglycaemic episodes and no need for titration) and a TZD (with the advantage of no weight gain and better overall tolerability). DPP-4 inhibitors also exert clinically relevant glucose-lowering effects compared with a placebo in patients treated with SU or TZD (of potential interest when metformin is either not tolerated or contraindicated), and as oral triple therapy with a good tolerability profile when added to a metformin-SU or pioglitazone-SU combination. Several clinical trials also showed a consistent reduction in HbA(1c) when DPP-4 inhibitors were added to basal insulin therapy, with no increased risk of hypoglycaemia. Because of the complex pathophysiology of type 2 diabetes and the complementary actions of glucose-lowering agents, initial combination of a DPP-4 inhibitor with either metformin or a glitazone may be applied in drug-naive patients, resulting in greater efficacy and similar safety compared with either drug as monotherapy. However, DPP-4 inhibitors were less effective than GLP-1 receptor agonists for reducing HbA(1c) and body weight, but offer the advantage of being easier to use (oral instead of injected administration) and lower in cost. Only one head-to-head trial demonstrated the non-inferiority of saxagliptin vs sitagliptin. Clearly, more trials of direct comparisons between different incretin-based therapies are needed. Because of their pharmacokinetic characteristics, pharmacodynamic properties (glucose-dependent glucose-lowering effect) and good overall tolerability profile, DPP-4 inhibitors may have a key role to play in patients with renal impairment and in the elderly. The role of DPP-4 inhibitors in the therapeutic armamentarium of type 2 diabetes is rapidly evolving as their potential strengths and weaknesses become better defined mainly through controlled clinical trials. [less ▲]Detailed reference viewed: 29 (1 ULg)
Prognostic impact of electrocardiographic signs in patients with Type 2 diabetes and cardiovascular disease: results from the PROactive study
; ; et al
in Diabetic Medicine : A Journal of the British Diabetic Association (2011), 28
Aims Although a resting electrocardiograph is broadly applied in clinical practice for evaluating patientswith Type 2 diabetes and cardiovascular disease, the independent prognostic relevance of ... [more ▼]
Aims Although a resting electrocardiograph is broadly applied in clinical practice for evaluating patientswith Type 2 diabetes and cardiovascular disease, the independent prognostic relevance of electrocardiographic signs has not thoroughly been examined. Methods Baseline 12-lead electrocardiographs available in 5231 of the 5238 participants of the PROactive trial were analysed for heart rate, heart rate corrected QT-interval, presence of atrial fibrillation ⁄ flutter, left axis deviation, right and left bundle branch block. The association of electrocardiographic signs with total mortality, the principal secondary composite endpoint (death, myocardial infarction and stroke) and serious adverse heart failure events was examined by Cox-regression analysis. Results Two hundred and twenty-three (4.3%) patients showed atrial fibrillation ⁄ flutter, 213 (4.1%) patients had right bundle branch block, 111 (2.1%) patients had left bundle branch block and 706 (13.5%) patients had left axis deviation. Mean cQT-interval was 418 ms ( 25 ms) and mean heart ratewas 72 ⁄min ( 14 ⁄ min). Inmultivariate adjusted analyses, heart rate and cQT-interval were significantly associated with mortality, the composite secondary endpoint and heart failure, whereas right and left bundle branch blockswere significantly associated with heart failure only. Left axis deviationwas associated with heart failure and atrial fibrillation ⁄ flutter was associated with mortality and heart failure in univariate but not multivariate analyses. Conclusion Easily assessable electrocardiographic signs such as heart rate, cQT-interval and bundle branch blocks were predictive for adverse outcome independently of multiple risk factor adjustment and should be considered in clinical care. [less ▲]Detailed reference viewed: 17 (0 ULg)
Novel Susceptibility Locus at 22q11 for Diabetic Nephropathy in Type 1 Diabetes
; ; et al
in PLoS ONE (2011), 9(11), 24053
Background: Diabetic nephropathy (DN) affects about 30% of patients with type 1 diabetes (T1D) and contributes to serious morbidity and mortality. So far only the 3q21–q25 region has repeatedly been ... [more ▼]
Background: Diabetic nephropathy (DN) affects about 30% of patients with type 1 diabetes (T1D) and contributes to serious morbidity and mortality. So far only the 3q21–q25 region has repeatedly been indicated as a susceptibility region for DN. The aim of this study was to search for new DN susceptibility loci in Finnish, Danish and French T1D families. Methods and Results: We performed a genome-wide linkage study using 384 microsatellite markers. A total of 175 T1D families were studied, of which 94 originated from Finland, 46 from Denmark and 35 from France. The whole sample set consisted of 556 individuals including 42 sib-pairs concordant and 84 sib-pairs discordant for DN. Two-point and multi-point non-parametric linkage analyses were performed using the Analyze package and the MERLIN software. A novel DN locus on 22q11 was identified in the joint analysis of the Finnish, Danish and French families by genome-wide multipoint nonparametric linkage analysis using the Kong and Cox linear model (NPLpairs LOD score 3.58). Nominal or suggestive evidence of linkage to this locus was also detected when the three populations were analyzed separately. Suggestive evidence of linkage was found to six additional loci in the Finnish and French sample sets. Conclusions: This study identified a novel DN locus at chromosome 22q11 with significant evidence of linkage to DN. Our results suggest that this locus may be of importance in European populations. In addition, this study supports previously indicated DN loci on 3q21–q25 and 19q13. [less ▲]Detailed reference viewed: 11 (1 ULg)
Haemodynamic changes during a squat test, pulsatile stress and indices of cardiovascular autonomic neuropathy in patients with long-duration type 1 diabetes.
PHILIPS, Jean-Christophe ; MARCHAND, Monique ; SCHEEN, André
in Diabètes & Métabolism (2011)
AIM: Cardiovascular autonomic neuropathy (CAN) and pulsatile stress are considered to be independent cardiovascular risk factors. This study compared haemodynamic changes during an active orthostatic test ... [more ▼]
AIM: Cardiovascular autonomic neuropathy (CAN) and pulsatile stress are considered to be independent cardiovascular risk factors. This study compared haemodynamic changes during an active orthostatic test in adult patients with type 1 diabetes (T1DM), using low versus high RR E/I ratios as a marker of CAN. METHODS: A total of 20 T1DM patients with low RR E/I ratios were compared with 20 T1DM patients with normal RR E/I ratios, matched for gender (1/1 ratio), age (mean: 46years) and diabetes duration (22-26years); 40 matched healthy subjects served as controls. All subjects were evaluated by continuous monitoring of arterial blood pressure (Finapres((R))) and heart rate using a standardized posture test (1-min standing, 1-min squatting, 1-min standing), thus allowing calculation of baroreflex gain. RESULTS: Compared with controls, T1DM patients showed lower RR E/I ratios, reduced baroreflex gains, higher pulsatile stress (pulse pressurexheart rate), greater squatting-induced pulse pressure rises, orthostatic hypotension and reduced reflex tachycardia. Compared with T1DM patients with preserved RR E/I ratios, T1DM patients with low RR E/I ratios showed reduced post-standing reflex tachycardia and baroreflex gain, and delayed blood pressure recovery, but no markers of increased pulsatile stress. Interestingly, decreased baroreflex gain was significantly associated with both pulsatile stress and microalbuminuria. CONCLUSION: The use of RR E/I ratios to separate T1DM patients allows the detection of other CAN markers during an orthostatic posture test, but with no significant differences in pulsatile stress or microalbuminuria. In this context, squatting-derived baroreflex gain appears to be more informative. [less ▲]Detailed reference viewed: 23 (1 ULg)
Squatting, a posture test for studying cardiovascular autonomic neuropathy in diabetes.
PHILIPS, Jean-Christophe ; MARCHAND, Monique ; SCHEEN, André
in Diabètes & Métabolism (2011), 37(6), 489-496
Cardiovascular autonomic neuropathy (CAN) is a frequent complication of diabetes mellitus, which is associated with increased morbidity and mortality. It involves both the parasympathetic and sympathetic ... [more ▼]
Cardiovascular autonomic neuropathy (CAN) is a frequent complication of diabetes mellitus, which is associated with increased morbidity and mortality. It involves both the parasympathetic and sympathetic nervous systems, and may be diagnosed by classical dynamic tests with measurements of heart rate (HR) and/or arterial blood pressure (BP). An original squat test (1-min standing, 1-min squatting, 1-min standing) was used with continuous monitoring of HR and BP, using a Finapres((R)) device. This active test imposes greater postural stress than the passive head-up tilt test, and provokes large changes in BP and HR that can be analyzed to derive indices of CAN. In healthy subjects, squatting is associated with BP increases and HR decreases (abolished by atropine: SqTv index), whereas the squat-stand transition is accompanied by a deep but transient drop in BP associated with sympathetic-driven tachycardia (abolished by propranolol: SqTs index). In diabetic patients with CAN, BP increases are accentuated during squatting whereas reflex bradycardia is reduced. When standing from squatting position, the fall in BP tends to be more pronounced and orthostatic hypotension more prolonged, while reflex tachycardia is markedly dampened. The baroreflex gain, similar to that calculated during pharmacological testing with vasodilator/vasopressor agents, can be derived by plotting pulse intervals (R-R) against systolic BP levels during the biphasic response following the squat-stand transition. The slope, which represents baroreflex sensitivity, is significantly reduced in patients with CAN. This discriminatory index allows study of the natural history of CAN in a large cohort of diabetic patients. [less ▲]Detailed reference viewed: 18 (0 ULg)
Facing up to the imperceptible perspiration. Modulatory influences by diabetic neuropathy, physical exercise and antiperspirant.
; ; Quatresooz, Pascale et al
in Skin Research & Technology (2011)
Background: Sweating is variably altered by physical exercise, diabetic neuropathy and antiperspirants. Methods: Skin temperature, skin surface water loss (SSWL), the Corneometer((R)) average capacitance ... [more ▼]
Background: Sweating is variably altered by physical exercise, diabetic neuropathy and antiperspirants. Methods: Skin temperature, skin surface water loss (SSWL), the Corneometer((R)) average capacitance (CMAC) and skin capacitance mapping (SCM) were measured before and after moderate physical exercise in 20 healthy subjects. The effect of 5% aluminium chloride hexahydrate (ACH) in a water solution was similarly tested. The same assessments were performed in 20 diabetic patients at rest. Results: Diabetic neuropathy appeared at rest as an increased (compensatory) SCM on the forearms without obvious modification on the hypohidrotic legs. On ACH sites after exercise, SCM revealed both a lowered number of active sweat glands and a lighter stratum corneum (SC) (dryness). In addition, CMAC and SSWL were decreased on ACH sites at rest and at completion of exercise. Conclusion: In diabetic neuropathy, the compensatory hyperhidrosis is more easily disclosed than the hypohidrosis. ACH affects both sweat excretion and the SC hydration. [less ▲]Detailed reference viewed: 21 (4 ULg)
RELATIONS ENTRE GAIN BARO-REFLEXE ET STRESS PULSATILE CHEZ LE PATIENT DIABETIQUE DE TYPE 1
SCHEEN, André ; MARCHAND, Monique ; PHILIPS, Jean-Christophe
in Archives des Maladies du Coeur et des Vaisseaux (2011), hors série 3Detailed reference viewed: 10 (0 ULg)
Diabete de type 2 et medicaments anti-inflammatoires: nouvelles perspectives therapeutiques?
Esser, Nathalie ; Paquot, Nicolas ; SCHEEN, André
in Revue Médicale Suisse (2011), 7(306), 1614-81620
It is now well accepted that a chronic, low-grade inflammation is observed in abdominal obesity, insulin resistance and type 2 diabetes mellitus, and that pro-inflammatory cytokines and oxidative stress ... [more ▼]
It is now well accepted that a chronic, low-grade inflammation is observed in abdominal obesity, insulin resistance and type 2 diabetes mellitus, and that pro-inflammatory cytokines and oxidative stress play a role in the pathogenesis of type 2 diabetes. These new findings raise the question of whether antiinflammatory strategies may have a place in the prevention and treatment of type 2 diabetes. This review article describes the results obtained in studies on patients with metabolic syndrome or type 2 diabetes aiming to test the metabolic effect of anti-inflammatory (salicylates, antagonists of interleukine-1, antagonists of tumor necrosis factor-alpha) and anti-oxydants (succinobucol) drugs. [less ▲]Detailed reference viewed: 104 (6 ULg)
Linagliptin for the treatment of type 2 diabetes (pharmacokinetic evaluation).
in Expert Opinion on Drug Metabolism & Toxicology (2011), 7(12), 1561-76
Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes (T2DM). The novel compound linagliptin has important different pharmacokinetic (PK ... [more ▼]
Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes (T2DM). The novel compound linagliptin has important different pharmacokinetic (PK) properties, when compared with previously commercialized DPP-4 inhibitors, which may offer some advantages in clinical practice. Linagliptin has a unique PK/pharmacodynamic (PD) profile and is the first DPP-4 inhibitor with a nonrenal elimination route. Therefore, it can be administered in patients with renal impairment without dose adjustment or monitoring of renal function. The drug has a low potential for drug-drug interactions (DDIs) and no clinically relevant ones were reported so far. Areas covered: An extensive literature search was performed to analyse primarily PK and secondarily PD characteristics of linagliptin in both healthy volunteers and patients with T2DM (treated with linagliptin as monotherapy or combined therapy). Updated information about linagliptin PK either after single administration (large dose range) or after chronic administration (steady state) were also included. A special focus has been put on DDIs and on PK/PD of linagliptin in patients with renal impairment. Expert opinion: Head-to-head comparative studies and/or increased clinical experience with DPP-4 inhibitors will determine the clinical advantage, if any, of one agent over another. [less ▲]Detailed reference viewed: 25 (3 ULg)
"The lower, the better": pas d'accord sur le rapport benefices/risques apres "ACCORD".
in Revue Médicale Suisse (2011), 7(306), 1603-4Detailed reference viewed: 16 (2 ULg)