Gallwitz B.,University of Tübingen |
Guzman J.,Celaya Center for Specialist Medicine |
Dotta F.,Endocrine and Metabolic science |
Guerci B.,Nancy University Hospital Center |
And 7 more authors.
The Lancet | Year: 2012
Background Glycaemic control deteriorates progressively over time in patients with type 2 diabetes. Options for treatment escalation remain controversial after failure of first-line treatment with metformin. We compared add-on exenatide with glimepiride for durability of glycaemic control in patients with type 2 diabetes inadequately controlled by metformin alone. Methods We did an open-label, randomised controlled trial at 128 centres in 14 countries between Sept 5, 2006, and March 29, 2011. Patients aged 18-85 years with type 2 diabetes inadequately treated by metformin were randomly assigned via a computer-generated randomisation sequence to receive exenatide twice daily or glimepiride once daily as add-on to metformin. Randomisation was stratified by predetermined categories of glycated haemoglobin (HbA 1C) concentration. The primary outcome was time to inadequate glycaemic control and need for alternative treatment, defined as an HbA 1c concentration of more than 9% after the first 3 months of treatment, or more than 7% at two consecutive visits after the first 6 months. Analysis was by intention to treat. This trial is registered with EudraCT, number 2005-005448-21, and ClinicalTrials.gov, number NCT00359762. Findings We randomly assigned 515 patients to the exenatide group and 514 to the glimepiride group, of whom 490 versus 487 were the intention-to-treat population. 203 (41%) patients had treatment failure in the exenatide group compared with 262 (54%) in the glimepiride group (risk difference 12·4 [95% CI 6·2-18·6], hazard ratio 0·748 [0·623-0·899]; p=0·002). 218 (44%) of 490 patients in the exenatide group, and 150 (31%) of 487 in the glimepiride group achieved an HbA 1c concentration of less than 7% (p<0·0001), and 140 (29%) versus 87 (18%) achieved concentrations of 6·5% and less (p=0·0001). We noted a significantly greater decrease in bodyweight in patients given exenatide than in those given glimepiride (p<0·0001). Five patients in each treatment group died from causes unrelated to treatment. Significantly fewer patients in the exenatide group than in the glimepiride group reported documented symptomatic (p<0·0001), nocturnal (p=0·007), and non-nocturnal (p<0·0001) hypoglycaemia. Discontinuation because of adverse events (mainly gastrointestinal) was significantly higher (p=0·0005) in the exenatide group than in the glimepiride group in the first 6 months of treatment, but not thereafter. Interpretation These findings provide evidence for the benefits of exenatide versus glimepiride for control of glycaemic deterioration in patients with type-2 diabetes inadequately controlled by metformin alone.
Liebl A.,Center for Diabetes and Metabolism |
Jones S.,James Cook University |
Benroubi M.,Polyclinic General Hospital |
Goday A.,Hospital Del Mar |
And 5 more authors.
Current Medical Research and Opinion | Year: 2011
Objectives: To examine insulin regimens and factors that affect glycaemic control at 6 months after initiation of insulin therapy in patients with type 2 diabetes mellitus. Research design and methods: Information on patients requiring insulin initiation as part of usual care was collected in a prospective, observational, open-label study in five European countries. Univariate and multiple regression analyses were used to investigate factors associated with HbA1c achieved at 6 months. Results: Mean HbA1c for all patients at baseline was 9.6 ± 1.8%. Long/intermediate-acting insulin only was most commonly initiated in France and Spain, while long/intermediate or pre-mixed formulations were initiated in Greece and UK. This was consistent with guidelines used in those countries and there was little change in insulin regimen at 6 months in these countries. In Germany, short-acting insulin only was favoured at baseline and there was a shift towards basal/bolus regimens at 6 months, which reflected the local guidelines for insulin initiation in Germany. Mean HbA1c reduction was greatest in Germany (-2.3%), which was the only country to achieve a mean of <7% at 6 months. In all countries, HbA1c achieved at 6 months was associated with baseline HbA1c. Differences between countries were seen for influence of factors such as BMI, duration of diabetes, insulin regimen, insulin dose and number of oral anti-diabetes drugs on HbA1c achieved. Explained variability for the factors ranged from 5.6% to 22.9%. Conclusions: Differences in insulin regimen were observed between countries, and appeared to reflect the guidelines and treatment regimens used. © 2011 Informa UK Ltd.
Gallwitz B.,University of Tübingen |
Bohmer M.,Practice for Diabetology |
Segiet T.,Practice for Diabetology |
Molle A.,Practice for Angiology and Diabetology |
And 5 more authors.
Diabetes Care | Year: 2011
OBJECTIVE - Hypoglycemia causes recurrent morbidity in patientswith type 2 diabetes. This study evaluated if exenatide twice daily (BID) was noninferior to premixed insulin aspart 70/30 BID (PIA) for glycemic control and associated with less hypoglycemia. RESEARCH DESIGN AND METHODS - In this open-label study, metformin-treated adults with type 2 diabetes were randomized to 26-week treatment with exenatide BID (4 weeks 5 mg, then 10 mg) or PIA. RESULTS - Exenatide BID (n = 181) was noninferior to PIA (n = 173) for A1C control (least squares [LS] mean change 21.0 vs. 21.14%; difference [95% CI] 0.14 [-0.003 to 0.291]) and associated with a lower risk for hypoglycemia (8.0 vs. 20.5%, P < 0.05). LS mean weight decreased by 4.1 kg and increased by 1.0 kg with PIA (P < 0.001). A total of 39.2 vs. 20.8% of patients reached the composite end point of A1C <7.0%, no weight gain, and no hypoglycemia (P < 0.001; post hoc analysis). CONCLUSIONS - In metformin-treated patients, exenatide BID was noninferior to PIA for glycemic control but superior for hypoglycemia and weight control. © 2011 by the American Diabetes Association.
Van De Vaart H.,University Utrecht |
Falconer C.,Karolinska Institutet |
Quail D.,Eli Lilly and Company |
Timlin L.,Eli Lilly and Company |
And 3 more authors.
Neurourology and Urodynamics | Year: 2010
Aims: To determine which patient characteristics, incontinence and non-incontinence related, are associated with the symptom severity scores of the Urogenital Distress Inventory (UDI) and the International Consultation on Incontinence Questionnaire Urinary Incontinence (ICIQ-UI); and to determine the association of both patient characteristics and symptom severity scores with quality-of-life scores of the Incontinence Impact Questionnaire (IIQ) and the Incontinence-Quality of Life (I-QOL) questionnaire. Methods: Women presenting with stress urinary incontinence (SUI) symptoms in primary and secondary care entered the Stress Urinary Incontinence Treatment Study (SUIT), an observational study evaluating the cost-effectiveness of duloxetine compared to other non-surgical treatments for SUI. At enrolment patients completed the UDI-6, the short form ICIQ-UI, the IIQ-7 and the I-QOL. Multivariate linear regressions were performed with the UDI-6, ICIQ-UI SF, IIQ-7, and I-QOL as outcomes. Results: The total number of incontinence episodes is the most significant explanatory variable of the two symptom questionnaire scores, but the UDI-6 score also reflects the type of incontinence. The variability of the condition-specific quality-of-life questionnaires is primarily explained by the symptom severity questionnaire scores. Although there is a high intercorrelation, both these symptom questionnaires independently contributed significantly to the IIQ-7 and I-QOL total scores. Conclusions: The UDI-6 and ICIQ-UI SF can be regarded as scientifically sound symptom questionnaires in UI evaluation; but they have differences. Since the UDI-6 and ICIQ-UI SF independently contribute to the quality-of-life scores, this suggests that in incontinence research symptom questionnaires should not focus only on incontinence, but on a broader range of urogenital symptoms. Neurourol. Urodynam. 29:348-353, 2010. Copyright © 2009 Wiley-Liss, Inc.
Cardozo L.,King's College |
Lange R.,Urogynecological Practice |
Voss S.,Lilly Research Laboratories |
Beardsworth A.,Lilly Research Laboratories |
And 3 more authors.
Current Medical Research and Opinion | Year: 2010
Objective: To evaluate short-and long-term safety and efficacy of duloxetine in women with predominant stress urinary incontinence (SUI). Research design and methods: The study was a 6-week, double-blind, randomised, parallel, placebo-controlled study followed by an uncontrolled open-label extension (OLE) run in 342 study centres in 16 European countries. Women with predominant SUI were randomly assigned to placebo (n1380) or duloxetine 40mg twice daily (n1378) for 6 weeks. Completers of the acute phase were enrolled in the OLE, which had a minimum duration of 6 weeks and ended, based on the approval status of duloxetine in the participating country. Clinical Trial Registry: www.clinicaltrials.gov; NCT00190996. Main outcome measures: The primary outcome measure was the change in incontinence episode frequency (IEF) over 6 weeks. Secondary outcome measures were the long-term maintenance of effect on IEF and Patient Global Impression of Improvement (PGI-I), the short-and long-term impact on quality of life using the Kings Health Questionnaire (KHQ), and the long-term safety of duloxetine. Results: After 6 weeks, the decrease in weekly IEF was significantly greater with duloxetine treatment compared to placebo (-50.0 vs.-29.9; p<0.001). The percentage of responders (defined as 50 decrease in IEF) was significantly higher with duloxetine treatment than with placebo (50.6 vs. 31.2; p<0.001). Duloxetine treatment was associated with improvements in weekly pad use (-31.4), PGI-I ratings (63.6), and KHQ score (-6.25) compared to placebo (-12.5, 48.5 and-3.13, respectively, all p<0.001). Treatment-emergent adverse events were significantly more common during duloxetine treatment (48.3) than placebo (33.3), (p<0.001). Of the 2290 patients continuing into the OLE, 1165 (42.2) completed the available duration, and 592 (21.5) discontinued because of an adverse event (percentages relative to total randomised patients). Long-term efficacy in the OLE was assessed over a 72-week period and was maintained over that time. However, the results should be interpreted within the context that better responding patients are more likely to remain on duloxetine, while patients responding poorly are more likely to discontinue over time. Conclusions: Duloxetine seems to be an efficacious treatment with an acceptable safety profile for women with SUI. Achieved improvement is maintained over the longer term in those women who remain on therapy. © 2010 Informa UK Ltd All rights reserved.
Schacht A.,Lilly Deutschland |
Escobar R.,Lilly Research Laboratories |
Wagner T.,Trilogy Writing and Consulting GmbH |
Wehmeier P.M.,Vitos Hospital for Psychiatry and Psychotherapy |
Wehmeier P.M.,University of Heidelberg
ADHD Attention Deficit and Hyperactivity Disorders | Year: 2011
Our aim was to evaluate the psychometric properties of the generic quality of life (QoL) scale Child Health and Illness Profile-Child Edition (CHIP-CE) by means of a combined analysis of atomoxetine clinical trials in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Individual patient-level data from five clinical trials were included in the combined analysis. Psychometric properties of the CHIP-CE were explored in terms of internal consistency and structure. Patients (n = 794) aged between 6 and 15 years (mean 9. 7) with mean baseline ADHD Rating Scale of 41. 8 ± 8. 04 were included. On average, 0. 7 (SD 2. 23) items were missing for the whole CHIP-CE. The internal consistency of the CHIP-CE assessed by Cronbach's alpha was good for all sub-domains at baseline and at endpoint. Considerable ceiling effects were only observed for the "restricted activity" sub-domain. No considerable floor effects were seen. The factor analysis supported the 12-factor solution for the sub-domains, but not the 5-factor solution for the domains. Our analyses were based on a large sample of non-US patients which allowed the measurement of clear changes in QoL over time. The results support that the CHIP-CE scale is psychometrically robust over time in terms of internal consistency and structure. © 2011 The Author(s).
PubMed | Tumorgenetik Bonn Kooperation fur Tumordiagnostik, Lilly Deutschland, Airway Research Center North, Lilly France and 10 more.
Type: Clinical Trial, Phase II | Journal: Lung cancer (Amsterdam, Netherlands) | Year: 2016
We investigated the feasibility of cisplatin or carboplatin combined with pemetrexed as adjuvant treatment in patients with completely resected Stage IB/II Non-Small-Cell Lung Cancer (NSCLC).Patients in this multicenter, open-label, parallel-group, non-comparative Phase 2 study were randomized (1:1) to pemetrexed (500 mg/m(2)) with either cisplatin (75 mg/m(2)) or carboplatin (AUC5) for 4 cycles of 21 days. The primary endpoint was treatment feasibility (defined as 4 cycles completed with no cycle delay >42 days and 2 dose reductions, with a median relative dose intensity (RDI) 95% [overall]; and no Grade 3 toxicities at the follow-up visit 30 days after last drug administration). Secondary objectives included overall survival (OS) and safety.We randomized 122 patients and treated 118. 71.9% (46/64) of patients in pemetrexed+cisplatin and 88.9% (48/54) in pemetrexed+carboplatin completed 4 cycles (median RDI >97% for all compounds). Neither treatment met the pre-defined feasibility level >60% of patients: 59.4% (95% confidence interval [CI]: 46.4;71.5) pemetrexed+cisplatin; 50.0% (95%CI: 36.1;63.9) in pemetrexed+carboplatin. In a post-hoc analysis considering only safety, both regimens were feasible with 81.3% (95%CI: 69.5;89.9) in pemetrexed+cisplatin and 90.7% (95%CI: 79.7;96.9) in pemetrexed+carboplatin. OS rates for both groups were 82-83% after 3 years and 80-83% after 5 years. Treatment-related Grade 3 adverse events (mostly hematological) were experienced by approximately 30% of patients in each group.Although the study did not meet the primary objective, both treatment groups demonstrated good safety-related feasibility and tolerability as adjuvant treatment in patients with completely resected Stage IB/II NSCLC.
PubMed | Lilly Deutschland and University of Heidelberg
Type: Journal Article | Journal: Journal of attention disorders | Year: 2015
To compare the reduction of ADHD symptoms under atomoxetine in patients with and without comorbid oppositional defiant disorder (ODD) or conduct disorder (CD) using a computer-based continuous performance test (cb-CPT) combined with an infrared motion tracking (MT) device.Secondary analysis of a placebo-controlled study in ADHD patients (6-12 years old) treated with atomoxetine (target dose: 1.2 mg/kg per day). Cb-CPT/MT scores were analyzed using ANCOVA (last observation carried forward [LOCF]).The data (N = 125) suggested a more pronounced atomoxetine effect in the group with comorbid ODD/CD as measured by all cb-CPT/MT parameters except for normalized variation of reaction time (nVRT).The results showed that atomoxetine reduced ADHD severity as measured by cb-CPT and MT parameters regardless of whether comorbid ODD/CD was present. The treatment effect of atomoxetine on hyperactivity appears to be more pronounced in the subgroup of patients with comorbid ODD/CD than in the subgroup without this comorbidity.
Wehmeier P.M.,Lilly Deutschland |
Schacht A.,Lilly Deutschland |
Barkley R.A.,SUNY Upstate Medical School |
Barkley R.A.,Medical University of South Carolina
Journal of Adolescent Health | Year: 2010
This review provides an overview as to how the social and emotional impairments involved in Attention-Deficit/Hyperactivity Disorder affect the quality of life of patients and their families. A model of three categories into which the emotional difficulties fall, and how they impair quality of life, is also presented. © 2010 Society for Adolescent Medicine.
Chapple C.R.,Sheffield Hallam University |
Roehrborn C.G.,Southwestern Medical Center at Dallas |
McVary K.,University of Illinois at Springfield |
Ilo D.,Lilly UK |
And 2 more authors.
European Urology | Year: 2015
Background The international prostate symptom score (IPSS) evaluates lower urinary tract symptoms (LUTS) in men with suspected benign prostatic hyperplasia (BPH); the total score does not differentiate between storage and voiding and is unevenly weighted (four questions [57%] on voiding, three questions [43%] on storage). Objective To evaluate the relative contributions of storage and voiding IPSS subscores to total IPSS at baseline and in response to treatment with tadalafil. Design, setting, and participants Integrated analysis of data from four placebo-controlled, 12-wk studies of tadalafil (5 mg once daily) in 1499 men with LUTS/BPH. Outcome measurements and statistical analysis Relationships between total IPSS and the storage and voiding subscores were assessed using graphical exploration and linear regression modelling. Linear modelling was performed for the baseline and endpoint and for changes in subscores. The optimal storage subscore to total IPSS (S:T) ratio for IPSS improvement was identified using nonparametric regression and gradient-descent optimisation. Results and limitations The contribution of storage and voiding subscores at baseline and endpoint was 38.8% and 61.2%, and 39.2% and 60.7%, respectively. This intuitive 40:60 storage-to-voiding ratio was similar at baseline and endpoint by treatment group and for changes in subscores, but spanned the entire range for individuals. Changes in total IPSS were greatest for a storage subscore percentage contribution to total IPSS of 42.7%. There was no statistical association between S:T ratio (≥40% vs <40%) at baseline and response to tadalafil. The main limitation was the use of unvalidated storage and voiding IPSS subscores. Conclusions A constant S:T ratio of 4:10 was observed at baseline and endpoint. The greatest effect on total IPSS was noted for an S:T percentage contribution of 42.7%. Tadalafil efficacy was unaffected by the level of storage dysfunction at baseline. Patient summary This analysis shows that for men with BPH, improvements during treatment with tadalafil apply to both storage and voiding symptoms at a constant ratio. The extent of storage dysfunction before treatment did not affect the response to treatment. © 2014 European Association of Urology.