P01-249-Weight change and metabolic effects of asenapine in placebo- or olanzapine-controlled studies

IntroductionWeight change and metabolic effects of atypical antipsychotics vary considerably.ObjectiveAssess weight and metabolic effects of asenapine in adults.AimDemonstrate that asenapine marketed doses are well tolerated compared with placebo or olanzapine.MethodsData were from pooled asenapine trials that used placebo (1748 patients; duration: 1−6 wk) and/or olanzapine (3430 patients; duration, 3−>100 wk) controls. Asenapine doses were 5 or 10 mg BID (2–20 mg BID in 2 studies); olanzapine doses were 5–20 mg QD. Post hoc inferential analyses based on ANOVA assessed change from baseline weight, body mass index, and fasting lipid and glucose levels.ResultsTable 1 summarizes the results.[Change From Baseline Weight and Metabolic Paramete]DiscussionThese post hoc pooled analyses support published reports and suggest asenapine was associated with moderate weight gain and increased fasting triglyceride and glucose levels vs placebo, but lower propensity for weight gain or increased serum lipids (ie, triglycerides, low-density lipoprotein, and cholesterol) vs olanzapine.

Download Full-text

Abstract 13946: Sleep Problems on Simvastatin Differentially Predict Weight Change in Men

Circulation ◽

10.1161/circ.130.suppl_2.13946 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Beatrice A Golomb ◽

Hayley J Koslik ◽

Alexis K Bui

Keyword(s):

Young Adults ◽

Weight Gain ◽

Weight Change ◽

Sleep Problems ◽

Metabolic Effects ◽

Muscle Loss ◽

Relative Contribution ◽

Age Related ◽

Baseline Weight ◽

Interaction Term

Background and Goal: Sleep problems were significantly increased on simvastatin ( simva ) (but not pravastatin) vs placebo in the UCSD Statin Study. Sleep problems on simva predicted glucose rise. Weight gain has also been reported as a statin side effect. We sought to capitalize on existing data to assess whether sleep problems on simva related to weight gain in men. Method: 442 men without known diabetes or CVD were randomized to simva 20mg or placebo for 6 mon. One hundred eighty and 186 completed single-item self-rating of change in sleep problems vs baseline ( Δslpprob ). Weight (lb) was measured at baseline and 6 mon. Missing 6 mon values were imputed. Analyses: A. Regressions stratified by treatment assessed prediction of weight change by Δslpprob, adjusted for baseline weight. B. Regressions assessed prediction of weight change by the interaction term of simva (vs placebo) x Δslpprob, adjusted for the components of the interaction and baseline weight. Since age-related muscle loss may complicate weight change in elderly; and young adults have low vulnerability to metabolic problems, analyses were repeated excluding these groups. Results: A. Increased sleep problems on simva predicted weight gain (significant), but on placebo predicted weight loss (nonsignificant). B. The Δslpprob x simva interaction term significantly predicted weight gain. When that was parceled out, simva, outside of the sleep relationship, negatively predicted weight change. Exclusion of young adults and elderly strengthened significance of findings (Table). Discussion: Sleep problems, which differentially arise on simva, differentially predict weight gain on simva. This expands the metabolic effects to which sleep problems on simva may contribute and might possibly favor mediation by sleep apnea (a reported complication of simva). Once the sleep problem effect is considered, simva use predicted weight loss . The relative contribution of fat vs muscle loss (vs other) requires exploration.

Download Full-text

M205. LONG-TERM SAFETY OF LUMATEPERONE (ITI-007): METABOLIC EFFECTS IN A 1-YEAR STUDY

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa030.517 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S214-S214

Author(s):

Andrew Satlin ◽

Suresh Durgam ◽

Kimberly E Vanover ◽

Robert E Davis ◽

Jason Huo ◽

...

Keyword(s):

Weight Gain ◽

Metabolic Profile ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Standard Of Care ◽

Metabolic Effects ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Increased Risk

Abstract Background Standard of care (SOC) treatments for schizophrenia are often associated with a spectrum of metabolic adverse effects including weight gain and increased risk of diabetes, hyperlipidemia, and hypertension. Identifying new schizophrenia treatments with a favorable weight gain and metabolic side effect profile is important in reducing patient morbidity, mortality, and improving patient outcomes Lumateperone (lumateperone tosylate, ITI-007) is a mechanistically novel agent for the treatment of schizophrenia that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. This distinct pharmacological profile may confer favorable tolerability with a low risk of adverse metabolic effects compared with SOC treatment. In 3 short-term trials in patients with acute exacerbation of schizophrenia, lumateperone was associated with minimal weight gain and few metabolic side effects. This analysis of a phase 3 open-label study evaluated the weight change and metabolic profile of lumateperone in patients with stable schizophrenia that were switched from SOC to lumateperone 42-mg treatment (ITI-007 60 mg) for up to 1 year. Methods The metabolic profile of lumateperone was evaluated in prospective and post hoc analyses of an open-label study (Study 303). This study comprised patients with stable schizophrenia that were switched from SOC treatment to lumateperone 42 mg for 1 year of treatment; the study is currently ongoing to evaluate patients with greater than 1-year lumateperone exposure. Change in weight and metabolic assessments were conducted in all patients who completed 1 year of treatment and in patients who were classified at baseline by body mass index (BMI) as overweight (BMI 25–30) or obese (BMI ≥30). Results In the 1-year open-label study, 602 patients received at least 1 dose of lumateperone 42 mg and were included in the safety population; 239 patients completed 1 year of treatment. Mean cholesterol (total and low-density lipoprotein [LDL]) significantly decreased from SOC baseline (total: −11.4 mg/dL, P<.001; LDL: −10.2 mg/dL, P<.001). Significant improvements in mean body weight from SOC baseline were observed during the 1-year lumateperone treatment (−2.1 kg, P<.001). Lumateperone treatment was also associated with significant reductions from SOC baseline in BMI (−0.67 kg/m2, P=.002) and waist circumference in both men (−3.21 cm, P<.001) and women (−3.28, P<.001). Potentially clinically significant (PCS; ≥7% change from baseline) weight loss occurred in 19% of the population. Similarly, a high percentage of obese (19%) and overweight patients (21%) showed PCS weight decrease from SOC baseline. Conversely, PCS weight gain was infrequent in all patients (5%) and in obese (4%) and overweight (3%) patients. Shift from overweight to normal BMI occurred in 28% of patients; shift in BMI from overweight to obese occurred in 4% of patients. Improvement in BMI from obese to overweight was observed in 21% of patients. Discussion In patients switched from SOC treatment, improved metabolic and weight parameters were observed following 1 year of treatment with lumateperone 42 mg. Marked improvements were seen in patients that were overweight or obese at SOC baseline. These results suggest that lumateperone 42 mg may be a promising new treatment for schizophrenia, with minimal metabolic risk.

Download Full-text

Efficacy and metabolic effects of lurasidone versus brexpiprazole in schizophrenia: a network meta-analysis

Journal of Comparative Effectiveness Research ◽

10.2217/cer-2018-0016 ◽

2018 ◽

Vol 7 (8) ◽

pp. 737-748 ◽

Cited By ~ 4

Author(s):

Daisy Ng-Mak ◽

Vanita Tongbram ◽

Kerigo Ndirangu ◽

Krithika Rajagopalan ◽

Antony Loebel

Keyword(s):

Weight Gain ◽

Acute Treatment ◽

Meta Analysis ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Similar Efficacy ◽

Metabolic Effects ◽

Low Density ◽

Relative Efficacy ◽

Efficacy Measures

Aim: To assess the relative efficacy and metabolic effects of lurasidone and brexpiprazole in the acute treatment of schizophrenia. Methods: Five lurasidone and three brexpiprazole trials were identified. In the absence of head-to-head trials, a Bayesian network meta-analysis comparing lurasidone and brexpiprazole was performed. Results: Nonstatistically significant differences in efficacy measures were observed between lurasidone and brexpiprazole. Significant differences favoring lurasidone for weight change (-0.69 kg; 95% CrI: -1.22 to -0.15), total cholesterol (-7.60 mg/dl; 95% CrI: -13.94 to -1.22), and low-density lipoprotein (-6.58 mg/dl; 95% CrI: -12.11 to -1.04) were observed, with a trend indicating half the risk of experiencing ≥7% weight gain. Conclusion: This network meta-analysis suggested that lurasidone had similar efficacy and fewer metabolic effects than brexpiprazole in patients with acute schizophrenia.

Download Full-text

Effect of Honey & Olive Oil Supplemented Bio-Yoghurt Feeding on Lipid Profile, Blood Glucose and Hematological Parameters in Rats

Current Nutrition & Food Science ◽

10.2174/1573401313666170905160124 ◽

2019 ◽

Vol 15 (2) ◽

pp. 140-147

Author(s):

Magdy M. Ismail ◽

El-Tahra M. Ammar ◽

Abd El-Wahab E. Khalil ◽

Mohamed Z. Eid

Keyword(s):

Body Weight ◽

Weight Gain ◽

Blood Glucose ◽

Olive Oil ◽

Body Weight Gain ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Low Density Lipoprotein Cholesterol

Background and Objective: Yoghurt, especially bio-yoghurt has long been recognized as a product with many health benefits for consumers. Also, honey and olive oil have considerable nutritional and health effects. So, the effect of administration of yoghurt made using ABT culture and fortified with honey (2 and 6%), olive oil (1 and 4%) or honey + olive oil (2+1 and 6+4% respectively) on some biological and hematological properties of rats was investigated.Methods:The body weight gain, serum lipid level, blood glucose level, serum creatinine level, Glutamic Oxaloacetic Transaminase (GOT) activity, Glutamic Pyruvic Transaminase (GPT) activity, leukocytes and lymphocytes counts of rats were evaluated.Results:Blending of bio-yoghurt with rats' diet improved body weight gain. Concentrations of Total plasma Cholesterol (TC), High-Density Lipoprotein cholesterol (HDL), Low-Density Lipoprotein cholesterol (LDL), Very Low-Density Lipoprotein cholesterol (VLDL) and Triglycerides (TG) significantly lowered in plasma of rats fed bio-yoghurt. Levels of TC, LDL, VLDL, and TG also decreased in rat groups feed bio-yoghurt supplemented with honey and olive oil. LDL concentrations were reduced by 10.32, 18.51, 34.17, 22.48, 43.30% in plasma of rats fed classic starter yoghurt, ABT yoghurt, ABT yoghurt contained 6% honey, ABT yoghurt contained 4% olive oil and ABT yoghurt contained 6% honey + 4% olive oil respectively. The blood glucose, serum creatinine, GOT and GPT values of rats decreased while white blood cells and lymphocytes counts increased by feeding bioyoghurt contained honey and olive oil.Conclusion:The findings enhanced the multiple therapeutic effects of bio-yoghurt supplemented with honey and olive oil.

Download Full-text

Effects of Weight Gain after 20 Years of Age and Incidence of Hyper-Low-Density Lipoprotein Cholesterolemia: The Iki Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD)

Journal of Clinical Medicine ◽

10.3390/jcm10143098 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3098

Author(s):

Shota Okutsu ◽

Yoshifumi Kato ◽

Shunsuke Funakoshi ◽

Toshiki Maeda ◽

Chikara Yoshimura ◽

...

Keyword(s):

Weight Gain ◽

General Population ◽

Ldl Cholesterol ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Population Based ◽

Lipid Lowering ◽

Low Density ◽

Obesity Hypertension ◽

Old Men

The aim of this study was to investigate the effects of long-term weight gain from the age of 20 on incidence of hyper-low-density-lipoprotein (LDL) cholesterolemia in the general population of Japanese people. Methods: We conducted a population-based retrospective cohort study using annual health checkup data for residents of Iki City, Nagasaki Prefecture, Japan. A total of 3179 adult (≥30 years old) men and women without hyper-LDL cholesterolemia at baseline, who underwent two or more health checkups were included in the analysis. Information on weight gain (≥10 kg) after 20 years of age was obtained using questionnaire. The outcome of this study was development of hyper-LDL cholesterolemia defined as LDL-cholesterol level ≥3.62 mmol/L and/or initiation of lipid-lowering medications. Results: During a mean follow-up period of 4.53 years, 665 of the 3179 participants developed hyper-LDL cholesterolemia (46.5/1000 person-years). The incidence of hyper-LDL cholesterolemia was higher in participants with a weight gain of ≥10 kg (55.3/1000 person-years) than among those with a weight gain of <10 kg (41.8/1000 person-years). This association remained statistically significant even after adjustment for age, sex, smoking, daily drinking, exercise, obesity, hypertension, and diabetes (multivariable hazard ratio 1.31, 95% confidence interval 1.08–1.58, p = 0.006). Conclusion: A weight gain of ≥10 after 20 years of age affected the development of hyper-LDL cholesterol regardless of age, sex, and obesity in a general population of Japanese.

Download Full-text

LDL receptor but not apolipoprotein E deficiency increases diet-induced obesity and diabetes in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2002.282.1.e207 ◽

2002 ◽

Vol 282 (1) ◽

pp. E207-E214 ◽

Cited By ~ 109

Author(s):

Sandra A. Schreyer ◽

Cynthia Vick ◽

Theodore C. Lystig ◽

Paul Mystkowski ◽

Renée C. LeBoeuf

Keyword(s):

Apolipoprotein E ◽

Low Density Lipoprotein ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Wild Type ◽

Glucose Levels ◽

Diet Induced Obesity ◽

Obesity And Diabetes ◽

Glucose And Lipid Homeostasis

The aim of this study was to determine whether phenotypes associated with type 2 diabetes are altered in dyslipidemic obese mice. C57BL/6 wild-type, low-density lipoprotein (LDL) receptor-deficient (LDLR−/−), and apolipoprotein E-deficient (apoE−/−) mice were fed a high-fat, high-carbohydrate diet (diabetogenic diet), and the development of obesity, diabetes, and hypertriglyceridemia was examined. Wild-type mice became obese and developed hyperglycemia, but not hypertriglyceridemia, in response to this diet. LDLR−/− mice fed the diabetogenic diet became more obese than wild-type mice and developed severe hypertriglyceridemia and hyperleptinemia. Surprisingly, glucose levels were only modestly higher and insulin levels and insulin-to-glucose ratios were not strikingly different from those of wild-type mice. In contrast, diabetogenic diet-fed apoE−/− mice were resistant to changes in glucose and lipid homeostasis despite becoming obese. These data suggest that modifications in lipoprotein profiles associated with loss of the LDL receptor or apoE function have profound and unique consequences on susceptibility to diet-induced obesity and type 2 diabetic phenotypes.

Download Full-text

Unwanted Hormonal and Metabolic Effects of Postoperative Adjuvant Mitotane Treatment for Adrenocortical Cancer

Cancers ◽

10.3390/cancers12092615 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2615 ◽

Cited By ~ 1

Author(s):

Vittoria Basile ◽

Soraya Puglisi ◽

Anna Calabrese ◽

Anna Pia ◽

Paola Perotti ◽

...

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Pharmacokinetic Interaction ◽

Metabolic Effects ◽

Therapeutic Drug ◽

Male Hypogonadism ◽

Adrenocortical Cancer ◽

Biochemical Alterations ◽

Biochemical Assessment ◽

Higher Doses

Mitotane is widely used for the treatment of adrenocortical cancer (ACC), although the drug-related toxicity complicates its use. The aim of this study is to assess comprehensively the different endocrine and metabolic unwanted effects of the drug, and to provide data on the supportive therapies. We retrospectively analyzed 74 ACC patients adjuvantly treated with mitotane for ≥12 months. During the treatment period (40 months, 12–195), 32.4% of patients needed replacement therapy for mineralocorticoid deficit, 36.2% for hypothyroidism and 34.3% for male hypogonadism. In fertile women, hypogonadism was uncommon, while 65.4% of women developed ovarian cysts. Although no significant change in low-density lipoprotein (LDL) was observed, statins were started in 50% of patients for a significant increase in total cholesterol and triglycerides. Dyslipidemia occurred early, after a median time of 6 months from mitotane start. Conversely, testosterone replacement was usually started after >2 years. In many cases, ranging from 29.4% to 50% according to the side effect, toxicity occurred well before the achievement of the target mitotane concentrations. Supportive therapies were able to revert the biochemical alterations induced by mitotane, although higher doses were needed for a likely pharmacokinetic interaction of exogenous steroids and statins with mitotane. In conclusion, adjuvant mitotane therapy is associated with a spectrum of unwanted effects encompassing the function of different endocrine glands and requires a careful clinical and biochemical assessment associated with the therapeutic drug monitoring.

Download Full-text

ASSOCIATION BETWEEN BLOOD LIPID PROFILE AND BLOOD GLUCOSE LEVELS IN MEN WITH CORONARY HEART DISEASE, METABOLIC SYNDROME, AND TYPE 2 DIABETES MELLITUS

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2013-5-29-33 ◽

2013 ◽

Vol 12 (5) ◽

pp. 29-33

Author(s):

S. A. Matveeva

Keyword(s):

Blood Glucose ◽

Lipid Profile ◽

Low Density Lipoprotein ◽

Fasting Blood Glucose ◽

Density Lipoprotein ◽

Blood Lipid ◽

Lipoprotein Cholesterol ◽

Blood Lipid Profile ◽

Glucose Levels ◽

Blood Glucose Levels

Aim.To study the associations between blood lipid profile and blood glucose levels in men with coronary heart disease (CHD), stable effort angina (SEA), metabolic syndrome (MS), and Type 2 diabetes mellitus (DM-2).Material and methods.The study included 82 men (mean age 50,5±0,9 years) with CHD, Functional Class I–III SEA, MS, and DM-2. The following lipid profile parameters were assessed: total cholesterol (TCH), triglycerides (TG), low-density lipoprotein cholesterol (LDL–CH), very low-density lipoprotein cholesterol (VLDL–CH), high-density lipoprotein cholesterol (HDL–CH), atherogenic index (AI), and triglyceride index (TGI), together with fasting blood glucose.Results.There were positive (direct) associations between higher levels (>90th percentile) of lipid profile parameters (TCH, TG, LDL–CH, VLDL– CH, HDL–CH, AI, TGI) and blood glucose, as well as between lower levels (≤10th percentile) of lipid profile parameters (TCH, TG, LDL–CH, VLDL– CH, AI, TGI) and blood glucose. At the same time, there were negative (inverse) associations between lower lipid levels (≤10th percentile of TCH, TG, LDL–CH, VLDL–CH, HDL–CH, AI, TGI) and higher glucose levels (>90th percentile), as well as between higher lipid levels (>90th percentile of TCH, TG, LDL–CH, VLDL–CH, HDL–CH, AI, TGI) and lower glucose levels (≤10th percentile).Conclusion.Dyslipidemia and hyperglycemia demonstrate synergetic proatherogenic effects in patients with CHD, SEA, MS, and DM-2, as suggested by significant heterogeneous (direct and inverse) associations between lipid profile parameters and fasting blood glucose. The results obtained provide an opportunity for the assessment of risk levels, prognosis, and need for pharmacological prevention and treatment in patients with combined cardiovascular pathology.

Download Full-text

Biological variability in serum vitamin E concentrations: relation to serum lipids

Clinical Chemistry ◽

10.1093/clinchem/42.11.1824 ◽

1996 ◽

Vol 42 (11) ◽

pp. 1824-1831 ◽

Cited By ~ 20

Author(s):

M Maes ◽

S Weeckx ◽

A Wauters ◽

H Neels ◽

S Scharpé ◽

...

Keyword(s):

Vitamin E ◽

Serum Lipids ◽

Low Density Lipoprotein ◽

Serum Vitamin ◽

Density Lipoprotein ◽

Low Density Lipoprotein Cholesterol ◽

Apo B ◽

Positive Time ◽

Index Of Individuality ◽

The Mean

Abstract The components of biological variation in serum vitamin E in relation to serum cholesterol, triglycerides, high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), apolipoprotein A-I (apo A-I), and apo B were examined in 26 healthy volunteers who had monthly blood samplings during one calendar year. The estimated CVs for vitamin E were: interindividual, 19.9%, and intraindividual, 11.9%; the index of individuality (I-index) was 0.59. The I-indices for all lipid variables were < 0.51. Serum concentrations of vitamin E, cholesterol, triglycerides, HDL-C, LDL-C, and apo B were lower in spring than in the other seasons. The peak-trough differences in the yearly variations, expressed as a percentage of the mean, were for vitamin E 14.5%, cholesterol 16.2%, triglycerides 14.5%, and LDL-C 24.3%. A significant common annual rhythm was expressed in vitamin E or lipid variables and in the changes in ambient temperature the weeks before blood sampling (inverse relations). There were highly significant positive time relations between serum vitamin E and cholesterol, triglycerides, and apo B. Subjects with higher homeostatic setpoints of cholesterol showed higher homeostatic setpoints of vitamin E, triglycerides, LDL-C, and apo B.

Download Full-text

Biological variability in concentrations of serum lipids: sources of variation among results from published studies and composite predicted values

Clinical Chemistry ◽

10.1093/clinchem/39.6.1012 ◽

1993 ◽

Vol 39 (6) ◽

pp. 1012-1022 ◽

Cited By ~ 54

Author(s):

S J Smith ◽

G R Cooper ◽

G L Myers ◽

E J Sampson

Keyword(s):

Serum Lipids ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Sampling Interval ◽

Lipoprotein Cholesterol ◽

Biological Variability ◽

Sources Of Variation ◽

Design Characteristics ◽

Predicted Values ◽

Analytical Variation

Abstract To obtain the best estimates of the average intraindividual biological variability (CVb) in the concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and triglyceride serum lipids in a person's blood, we evaluated results from 30 studies published from 1970 to 1992. The usually more applicable random-effects model estimated an average CVb of 6.1% for TC, 7.4% for HDLC, 9.5% for LDLC, and 22.6% for triglyceride. Composite estimates of the average CVb from all evaluated published studies by different models of estimation ranged from 6.0% to 6.4% for TC, from 6.2% to 7.5% for HDLC, from 7.0% to 9.6% for LDLC, and from 22.4% to 22.9% for triglyceride. Two important factors influenced the reported biological variation of the study subjects: (a) the magnitude of the variability of the analytical method used and (b) the design characteristics of the study--primarily the number of subjects, the sampling interval, and the number of measurements per subject. For TC, we found a statistically significant positive correlation between the reported mean CVb and both the number of study subjects and the analytical variation. For TC and LDLC we estimate CVb as a function of the study design features. The number of patient specimens required to obtain reliable estimates for serum lipid concentrations are determined from the CVb and the current analytical variation.

Download Full-text