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Bushe C.J.,Eli Lilly and Company | Slooff C.J.,University of Groningen | Slooff C.J.,Lilly United States | Haddad P.M.,University of Manchester | Karagianis J.L.,Memorial University of Newfoundland
Journal of Clinical Psychiatry | Year: 2012

Background: Weight change data from randomized clinical trials are often of limited duration and trials do not always report a full range of clinically relevant categorical end points. Method: We conducted a post hoc analysis of data from the observational Worldwide Schizophrenia Outpatient Health Outcomes database (2000-2005) on weight change in 4,626 patients completing 3 years of antipsychotic monotherapy with amisulpride, clozapine, olanzapine, quetiapine, risperidone, and oral and depot first-generation antipsychotics (FGAs). Reported outcomes included mean and categorical weight changes and the trajectories of different measures of weight change. Results: Mean weight gain was lowest with amisulpride (1.8 kg; 95% CI, 0.2-3.3) and highest with olanzapine (4.2 kg; 95% CI, 3.9-4.5). Weight change for all antipsychotics was most rapid during the first 6 months; subsequent weight change was slower but did not plateau. All drugs showed considerable individual variation in weight change. The proportion losing ≥ 7% of their baseline bodyweight was highest with quetiapine (10%; 95% CI, 7%-16%) and lowest with depot FGAs (5%; 95% CI, 3%-10%). Between 7% and 15% of patients moved into an overweight or obese body mass index (kg/m2) category (≥ 25). Conclusions: The degree of weight gain varied between antipsychotics. All antipsychotics were associated with significant (≥ 7%) weight loss and gain from baseline. The mean rate of weight gain was maximal during the first 6 months but continued over 3 years without a plateau in this specific cohort. Patients should receive regular monitoring of weight throughout treatment. © Copyright 2012 Physicians Postgraduate Press, Inc.

Krege J.H.,Lilly United States | Lane N.E.,University of California at Davis | Harris J.M.,Eli Lilly and Company | Miller P.D.,University of Colorado at Denver | Miller P.D.,Colorado Center for Bone Research
Osteoporosis International | Year: 2014

Postmenopausal women with severe osteoporosis may require treatment with the bone anabolic drug teriparatide. While changes in bone mineral density (BMD) are one measure of response, BMD changes often require a minimum of one year to observe measureable changes. Biochemical markers of bone turnover change within 1 to 3 months of initiating osteoporosis therapy. Monitoring with a marker such as procollagen type I N propeptide (PINP), an osteoblast-derived protein, during teriparatide treatment may provide clinically useful information for managing patients with osteoporosis. Clinical trials have shown consistent increases in PINP within 3 months of initiating teriparatide, increases that are significantly greater than placebo and significantly different from baseline. Increases in PINP concentrations during teriparatide treatment correlate well with increases in skeletal activity assessed by radioisotope bone scans and quantitative bone histomorphometry parameters. Individuals treated with teriparatide in clinical trials usually experienced an increase in PINP > 10 mcg/L from baseline, while those given placebo usually did not. In the clinical setting, patients experiencing a significant increase in PINP > 10 mcg/L after initiating teriparatide therapy may receive an earlier confirmation of anabolic effect, while those who do not may be assessed for adherence, proper injection technique, or undetected secondary conditions that might mitigate an anabolic response. PINP monitoring may provide information supplemental to BMD monitoring and be a useful aid in managing patients receiving anabolic osteoporosis treatment in the same way that biochemical markers of bone resorption are useful in monitoring antiresorptive therapy. This review examines PINP as a biological response marker during teriparatide treatment for osteoporosis. © 2014 The Author(s).

Ioachimescu A.G.,Emory University | Brennan D.M.,Cleveland Clinic | Hoar B.M.,Cleveland Clinic | Hoogwerf B.J.,Cleveland Clinic | Hoogwerf B.J.,Lilly United States
Obesity | Year: 2010

The BMI is the most frequently used marker to evaluate obesity-associated risks. An alternative continuous index of lipid over accumulation, the lipid accumulation product (LAP), has been proposed, which is computed from waist circumference (WC, cm) and fasting triglycerides (TGs) (mmol/l): (WC 65) × TG (men) and (WC 58) × TG (women). We evaluated LAP and BMI as predictors of mortality in a high-risk cohort. Study population included 5,924 new consecutive patients seen between 1995 and 2006 at a preventive cardiology clinic. Fifty-eight percent of patients were discordant for their LAP and BMI quartiles. Patients whose LAP quartile was greater than BMI quartile had higher mortality compared with those with LAP quartile was lower than BMI quartile (8.2 vs. 5.4% at 6 years, P = 0.007). After adjustment for age, gender, smoking, diabetes mellitus, blood pressure, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C), (ln)LAP was independently associated with mortality (hazard ratio (HR) = 1.46, P 0.001). BMI was not associated with increased mortality (HR = 1.06, P = 0.39). Adding LAP to a model including traditional risk factors for atherosclerosis increased its predictive value (C statistic 0.762 vs. 0.750, P = 0.048). Adding BMI to the same model did not change its predictive value (0.749 vs. 0.750, P = 0.29). Subgroup analyses showed that LAP predicted mortality in the nondiabetic patients (adjusted HR for (ln)LAP 1.64, P 0.001), but did not reach significance in the diabetic patients (HR = 1.21, P = 0.11). In conclusion, LAP and not BMI predicted mortality in nondiabetic patients at high risk for cardiovascular diseases. LAP may become a useful tool in clinical practice to stratify the risk of unfavorable outcome associated with obesity. © 2009 The Obesity Society.

Clemow D.B.,Lilly United States | Bushe C.J.,Eli Lilly and Company
Journal of Psychopharmacology | Year: 2015

This article reviews data providing new insight into the trajectory of response and maintenance of response of atomoxetine in the treatment of child and adult attention-deficit hyperactivity disorder (ADHD). This nonsystematic review includes: onset of action and duration of effect, response rate, effect size, time to optimal response and norepinephrine transporter blockade biomarker data. Atomoxetine can have an onset of action within 1-2 weeks of starting treatment, but there is an incrementally increasing response for up to 24 weeks or longer. Responder rates and effect sizes are similar to methylphenidate. Upon treatment discontinuation, relapse rates are lower than expected. In adults, 50% maintain their response for at least 6 months after stopping atomoxetine, following 6 months of treatment. Single-dose atomoxetine can provide 24-hour efficacy, despite a 5-hour plasma half-life. Hypotheses can be generated relating to neuroadaptive changes, to explain these findings. Atomoxetine has a trajectory of response that is incremental over a long period of time, with a greater than expected maintenance of response. This has implications for physician atomoxetine dosing and efficacy assessment, patient education and outcomes, and for clinical trial design and assessment of comparative efficacy with stimulant medications. © The Author(s) 2015.

Blak B.T.,Cegedim Strategic Data Medical Research Ltd | Smith H.T.,Lilly UK | Hards M.,Cegedim Strategic Data Medical Research Ltd | Curtis B.H.,Lilly United States | Ivanyi T.,Lilly Hungary
Diabetic Medicine | Year: 2012

Aims To describe patients with Type 2 diabetes mellitus treated with basal insulin, with or without oral antidiabetics in UK primary care, and evaluate insulin treatment patterns and factors explaining changes in therapy. Methods Retrospective analysis of patients with Type 2 diabetes within The Health Improvement Network UK primary care database. Patients receiving basal insulin between January and June 2006 were followed until July 2009. Results Analysis included 3185 patients, mean age 65.6years [standard deviation (SD) 12.4], 50.9% men, median diabetes duration 9.6years, median basal insulin use 1.3years, 86.5% had received oral antidiabetics in the previous 12months. Mean follow-up was 2.9years (SD 1.0), 59.8% patients maintained basal insulin throughout follow-up with a mean HbA1C of 69mmol/mol (SD 19; 8.4%, SD 1.7) at baseline and 65mmol/mol (SD 17; 8.1%, SD 1.6) during follow-up. During follow-up, 6.9% of patients discontinued, 19.3% intensified with and 14.1% switched to prandial or premixed insulin. Patients who intensified (prandial) had a mean HbA1c of 77mmol/mol (SD 18; 9.2%, SD 1.6) before change and a mean HbA1c of 71mmol/mol (SD 21; 8.6%, SD 2.0) at the end of the study. Those switching to premixed insulin had a mean HbA1c of 80mmol/mol (SD 18; 9.5%, SD 1.7) before change and a mean HbA1c of 69mmol/mol (SD 17; 8.5%, SD 1.5) at the end of the study. Increasing HbA1c and longer diabetes duration explained intensification and switch. Conclusions The majority of patients had HbA1c above the 53mmol/mol (<7%) target at baseline and post-intensification/switch. The HbA1c levels were reduced by intensification/switch suggesting that insulin changes did have some impact. Most patients did not change insulin treatment despite having higher than recommended HbA1c levels. Reasons for not changing treatment in face of unsatisfactory clinical outcomes are unclear. Further research is warranted to explore barriers towards therapy change. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

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