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Effects of Curcuminoids Plus Piperine on Glycemic, Hepatic and Inflammatory Biomarkers in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind Placebo-Controlled Trial.
Panahi, Y, Khalili, N, Sahebi, E, Namazi, S, Simental-Mendía, LE, Majeed, M, Sahebkar, A
Drug research. 2018;(7):403-409
Abstract
INTRODUCTION Curcuminoids have been shown to reduce glycemia and related complications in diabetes. In the present study, we evaluated the impact of curcuminoids plus piperine administration on glycemic, hepatic and inflammatory biomarkers in type 2 diabetes (T2D) patients. METHODS T2D patients aged 18-65 years were enrolled in a randomized double-blind placebo-controlled trial and randomly allocated to standard-of-care treatment and dietary advises plus either curcuminoids (daily dose of 500 mg/day co-administered with piperine 5 mg/day) or placebo for a period of 3 months. Glycemic, hepatic and inflammatory parameters were measured at baseline and final conditions. RESULTS A total of 100 subjects (50 in each group) completed the 3-month period of trial. A significant reduction was found in serum levels of glucose (-9±16 mg/dL vs. -3±11 mg/dL in curcuminoids and placebo groups, respectively; p=0.048), C-peptide (-0.6±0.8 ng/mL vs. 0.02±0.6 ng/mL; p<0.001) and HbA1c (-0.9±1.1% vs. -0.2±0.5%; p<0.001) after curcuminoids supplementation versus placebo group. Additionally, participants in the intervention group showed lower serum alanine aminotransferase (-2±6 vs. -1±5; p=0.032) and aspartate aminotransferase (-3±5 vs. -0.3±4; p=0.002) levels compared with the placebo group. Finally, no significant differences in high-sensitivity C-reactive protein (hs-CRP) concentrations were observed between curcuminoids and placebo groups (p>0.05). CONCLUSION The results of the present trial revealed a beneficial effect of curcuminoids plus piperine supplementation on glycemic and hepatic parameters but not on hs-CRP levels in T2D patients.
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Comparison of effects of anagliptin and alogliptin on serum lipid profile in type 2 diabetes mellitus patients.
Kurozumi, A, Okada, Y, Arao, T, Kobayashi, T, Masuda, D, Yamashita, S, Tanaka, Y
Journal of diabetes investigation. 2018;(2):360-365
Abstract
INTRODUCTION Anagliptin (ANA) improves dyslipidemia in addition to blood glucose levels. However, there are no comparative studies on the effects of ANA and other dipeptidyl peptidase-4 inhibitors on serum lipid profile. We compared the effects of ANA on serum lipid profile with those of alogliptin (ALO) in type 2 diabetes mellitus outpatients. MATERIALS AND METHODS The study participants were 87 type 2 diabetes mellitus patients who had been treated with dipeptidyl peptidase-4 inhibitors for ≥8 weeks and had a low-density lipoprotein cholesterol (LDL-C) level of ≥120 mg/dL. Participants were switched to either 200 mg/day ANA or 25 mg/day ALO for 24 weeks. RESULTS There was no significant difference in percentage change in LDL-C level at 24 weeks between the ANA and ALO groups. Treatment with ANA for 12 weeks significantly decreased LDL-C levels, one of the secondary end-points. Treatment with ANA for 24 weeks significantly improved apolipoprotein B-100 levels, and the percentage change in LDL-C levels at 24 weeks correlated significantly with the percentage change in apolipoprotein B-100 levels in the ANA group. CONCLUSIONS The LDL-C-lowering effects of ANA and ALO at 24 weeks were almost similar in patients with type 2 diabetes mellitus. However, the results showed a tendency for a decrease in LDL-C level at 24 weeks in the ANA group, and that such improvement was mediated, at least in part, through the suppression of apolipoprotein B-100 synthesis.
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Pimavanserin: Potential Treatment For Dementia-Related Psychosis.
Cummings, J, Ballard, C, Tariot, P, Owen, R, Foff, E, Youakim, J, Norton, J, Stankovic, S
The journal of prevention of Alzheimer's disease. 2018;(4):253-258
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Abstract
Psychosis is common across dementia types with a prevalence of 20% to 70%. Currently, no pharmacologic treatment is approved for dementia-related psychosis. Atypical antipsychotics are frequently used to treat these disorders, despite significant safety concerns. Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved in the U.S. for treating hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Patients in the pimavanserin group experienced a significant (p=0.001) improvement in Scale for the Assessment of Positive Symptoms - Parkinson's disease (SAPS-PD) scores vs. placebo. In a subgroup analysis of patients with cognitive impairment (MMSE score ≥21 but ≤24), the observed improvement on the SAPS-PD with pimavanserin (N=50) was also significant (p=0.002) and larger than in the overall study population without an adverse effect on cognition. In a Phase 2 study with pimavanserin in Alzheimer's disease psychosis, pimavanserin significantly (p=0.045) improved psychosis at Week 6 vs. placebo on the NPI-NH Psychosis Score (PS). In a prespecified subgroup of patients with a baseline NPI-NH PS ≥12, a substantively larger treatment effect (p=0.011) was observed vs. participants with NPI-NH PS <12. The results of these studies in cognitively impaired patients with PDP provided the scientific foundation for an ongoing study of pimavanserin for treating patients with dementia-related psychosis associated with the most common neurodegenerative disorders. The study uses a relapse-prevention design with the endpoint of time-to-relapse of psychosis to evaluate the long-term efficacy and safety of pimavanserin as a potential treatment for hallucinations and delusions of dementia-related psychosis.
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Pathophysiology of drug induced weight and metabolic effects: findings from an RCT in healthy volunteers treated with olanzapine, iloperidone, or placebo.
Ballon, JS, Pajvani, UB, Mayer, LE, Freyberg, Z, Freyberg, R, Contreras, I, Rosenbaum, M, Leibel, RL, Lieberman, JA
Journal of psychopharmacology (Oxford, England). 2018;(5):533-540
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Abstract
Second generation antipsychotics are prescribed for an increasing number of psychiatric conditions, despite variable associations with weight gain, dyslipidemia, and impaired glucose tolerance. The mechanism(s) of the apparent causal relationships between these medications and metabolic effects have been inadequately defined and are potentially confounded by genetic risk of mental illness, attendant lifestyle, and concomitant medications. Therefore, we conducted a study in which 24 healthy volunteers were randomized to olanzapine (highly weight-gain liability), iloperidone (less weight-gain liability), or placebo treatment for 28 days under double-blind conditions. We hypothesized that antipsychotics induce weight gain primarily through increased caloric intake, which causes secondary dyslipidemia and insulin resistance. Subjects were phenotyped pre- and post-treatment for body weight, adiposity by dual energy X-ray absorptiometry, energy expenditure by indirect calorimetry, food intake, oral glucose tolerance, plasma lipids, glucose, insulin, and other hormones. We found significantly increased food intake and body weight but no change in energy expenditure in olanzapine-treated subjects, with associated trends towards lipid abnormalities and insulin resistance the extent of which were presumably limited by the duration of treatment. Iloperidone treatment led to modest non-significant and placebo no weightgain, lipid increases and alterations in insulin metabolism. We conclude that second generation antipsychotic drugs, as represented by olanzapine, produce their weight and metabolic effects, predominantly, by increasing food intake which leads to weight gain that in turn induces metabolic consequences, but also through other direct effects on lipid and glucose metabolism independant of food intake and weight gain.
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The Effect of the Association between Donepezil and Choline Alphoscerate on Behavioral Disturbances in Alzheimer's Disease: Interim Results of the ASCOMALVA Trial.
Carotenuto, A, Rea, R, Traini, E, Fasanaro, AM, Ricci, G, Manzo, V, Amenta, F
Journal of Alzheimer's disease : JAD. 2017;(2):805-815
Abstract
BACKGROUND Behavioral and psychological symptoms of dementia (BPSD) are a group of psychological reactions, psychiatric symptoms, and behaviors commonly found in Alzheimer's disease (AD). Four clusters of BPSD have been described: mood disorders (depression, anxiety, and apathy), psychotic symptoms (delusions and hallucinations), aberrant motor behaviors (pacing, wandering, and other purposeless behaviors), and inappropriate behaviors (agitation, disinhibition, and euphoria). Most of them are attributed to acetylcholine deficiency. OBJECTIVE To evaluate if a higher amount of acetylcholine obtained by associating donepezil and choline alphoscerate might have a favorable effect on BPSD. METHODS BPSD were measured at baseline and after 24 months in 113 mild/moderate AD patients, included in the double-blind randomized trial ASCOMALVA, by the Neuropsychiatric Inventory (NPI). Two matched groups were compared: group A treated with donepezil (10 mg/day) plus choline alphoscerate (1200 mg/day), and group B treated with donepezil (10 mg/day) plus placebo. RESULTS Data of NPI revealed a significant decrease of BPSD severity and distress of the caregiver in patients of group A compared with group B. Mood disorders (depression, anxiety and apathy) were significantly decreased in subjects treated with donepezil and choline alphoscerate, while their severity and frequency was increased in the other group. CONCLUSIONS Patients treated with donepezil plus choline alphoscerate showed a lower level of behavioral disturbances than subjects treated with donepezil only, suggesting that the association can have beneficial effects.
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Fixed-dose combination of alogliptin/pioglitazone improves glycemic control in Japanese patients with type 2 diabetes mellitus independent of body mass index.
Aoki, C, Suzuki, K, Kuroda, H, Sagara, M, Shimizu, M, Kasai, K, Aso, Y
Nagoya journal of medical science. 2017;(1):9-16
Abstract
This study investigated the effects of switching from combination therapy with either alogliptin (Alo) or pioglitazone (Pio) to fixed-dose combination therapy (FDCT) with alogliptin and pioglitazone (Alo-Pio FDCT). The usefulness and efficacy of Alo-Pio FDCT were investigated. A total of 50 outpatients with type 2 diabetes mellitus (T2DM) treated with Alo and 47 outpatients with T2DM treated with Pio were switched to Alo-Pio FDCT, and its efficacy and usefulness were evaluated. Significant improvements were observed in hemoglobinA1c (HbA1c), alanine transaminase (ALT), and γ-glutamyl transpeptidase (GGT) levels after switching to Alo-Pio FDCT for 16 weeks in both groups. Only the group switching from Alo to Alo-Pio FDCT showed significant improvements in high-density lipoprotein cholesterol (HDL) levels and triglyceride levels. In a multivariate logistic regression model of the variation in the change of HbA1c at 16 weeks, ALT and GGT were independent predictors of the change of HbA1c at 16 weeks. In addition, the switch to Alo-Pio FDCT improved glycemic control to a certain degree regardless of BMI. Switching from either Alo or Pio to Alo-PIO FDCT may, unlike monotherapy with a DPP-4 inhibitor, be effective for patients with T2DM regardless of whether they are obese or lean.
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Add on DPP-4 inhibitor alogliptin alone or in combination with pioglitazone improved β-cell function and insulin sensitivity in metformin treated PCOS.
Jensterle, M, Goricar, K, Janez, A
Endocrine research. 2017;(4):261-268
Abstract
PURPOSE Impaired β-cell function remains unaddressed in PCOS. The aim of the study was to evaluate whether dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin (ALO) alone or in combination with pioglitazone (PIO) improves β-cell function along with insulin resistance (IR) in metformin (MET) treated obese women with PCOS with persistent IR. MATERIALS AND METHODS In 12-week randomized study, ALO 25 mg QD (n=15) or ALO 25 mg QD and PIO 30 mg QD (n=15) was added to MET 1000 mg BID in PCOS women (aged 34.4 ± 6.5 years, BMI 39.0 ± 4.9 kg/m2, HOMA-IR 4.82 ± 2.52, mean ± SD). Model derived parameters of glucose homeostasis from the meal tolerance test (MTT) were determined. The ability of the β-cell function was assessed by the adaptation index (AI). RESULTS MET-ALO and MET-ALO-PIO resulted in a significant decrease of HOMA-IR (by 1.6±2.3 (p=0.039) and 2.9±3.3 (p=0.001), respectively) and an increase in insulin sensitivity (IS) after meal ingestion (oral glucose IS) by 31.4±97.5 ml·min-1·m-2 (p=0.007) vs 39.0±58.1 ml·min-1·m-2 (p=0.039), respectively. AI across the entire group was significantly improved from 329.6±200.6 to 442.5±303.9 (p=0.048). CONCLUSIONS ALO alone and in combination with PIO improved IR along with dynamic IS and meal related β-cell function when added to MET treated PCOS.
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The Effect of Remifentanil on Succinylcholine Induced Changes in Serum Potassium and Creatine Kinase: A Prospective Randomized Double blind Study.
Nasseri, K, Shami, S, Shirmohammadi, M, Sarshivi, F, Ghadami, N
Acta bio-medica : Atenei Parmensis. 2017;(3):276-280
Abstract
BACKGROUND AND AIM OF THE WORK Succinylcholine is still included as drugs favored by anesthetists because of its rapid onset and short duration of action. However, it can bring about complications such as hyperkalemia and increased serum creatine phosphokinase (CPK). This study aims at evaluating the effects of remifentanil on succinylcholine-induced postoperative changes in serum potassium and CPK. METHODS In this study, 59 patients with short term lower abdominal surgery were randomly divided into two groups. In the first group (control group), 2 ml normal saline was used before injecting anesthetic drugs while in the second group (study group), 1 mcg/kg of remifentanil was injected. The patients were anesthetized with a combination of fentanyl (1 mg/kg) and propofol (2 mg/kg). Besides, succinylcholine (1.5 mg/kg) was used for muscle relaxation and tracheal intubation. Serum potassium (before and 5 min after tracheal intubation), CPK (before anesthetic injection and 24 h after surgery) and hemodynamic parameters (including systolic, diastolic and mean arterial blood pressure and heart rate) were recorded. RESULTS Serum levels of potassium and CPK before and after induction of anesthesia showed no significant difference in both groups. Systolic, diastolic, and mean arterial blood pressure and heart rate in both groups after induction significantly changed. Compared to saline, remifentanil significantly stabilized hemodynamic changes after intubation. CONCLUSIONS The results suggest that remifentanil has no prophylactic effect on succinylcholine-induced CPK and potassium levels. However, it improves stability of hemodynamic variables.
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Efficacy and safety of alogliptin in patients with type 2 diabetes mellitus: A multicentre randomized double-blind placebo-controlled Phase 3 study in mainland China, Taiwan, and Hong Kong.
Pan, C, Han, P, Ji, Q, Li, C, Lu, J, Yang, J, Li, W, Zeng, J, Hsieh, AT, Chan, J
Journal of diabetes. 2017;(4):386-395
Abstract
BACKGROUND This study determined the efficacy and safety of once-daily oral alogliptin in patients from mainland China, Taiwan, and Hong Kong with type 2 diabetes mellitus. METHODS In this Phase 3 multicenter double-blind placebo-controlled 16-week trial, 506 patients were randomized to receive once-daily alogliptin 25 mg or placebo: 185 in the monotherapy group, 197 in the add-on to metformin group, and 124 in the add-on to pioglitazone group. The primary efficacy variable was the change from baseline (CFB) in HbA1c at Week 16; other efficacy measures included CFB to Week 16 in fasting plasma glucose (FPG), incidence of marked hyperglycemia (FPG ≥11.1 mmol/L), and the incidence of clinical HbA1c ≤6.5 % (48 mmol/mol) and ≤7.0 % (53 mmol/mol) at Week 16. Safety was assessed throughout the trial. RESULTS Alogliptin monotherapy provided a significantly greater decrease in HbA1c from baseline to Week 16 compared with placebo (-0.58 %; 95 % confidence interval [CI] -0.78 %, -0.37 %; P < 0.001). As an add-on to metformin or pioglitazone, alogliptin also significantly decreased HbA1c compared with placebo (-0.69 % [95 % CI -0.87 %, -0.51 %; P < 0.001] and -0.52 % [95 % CI -0.75 %, -0.28 %; P < 0.001], respectively). In any treatment group versus placebo, alogliptin led to greater decreases in FPG (P ≤ 0.004) and a higher percentage of patients who achieved an HbA1c target of ≤6.5 % and ≤7.0 % (P ≤ 0.003). No weight gain was observed in any treatment group. A similar percentage of patients experienced drug-related, treatment-emergent adverse events in the alogliptin and placebo arms. Four and two patients in the alogliptin and placebo arms, respectively, experienced mild or moderate hypoglycemia. CONCLUSIONS Alogliptin 25 mg once daily reduced HbA1c and FPG and enhanced clinical response compared with placebo when used as monotherapy or as an add-on to metformin or pioglitazone. Therapy with alogliptin was well tolerated.
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The Effects of (-)-OSU6162 on Chronic Fatigue in Patients With Traumatic Brain Injury: A Randomized Controlled Trial.
Berginström, N, Nordström, P, Schuit, R, Nordström, A
The Journal of head trauma rehabilitation. 2017;(2):E46-E54
Abstract
OBJECTIVE To examine the effects of the monoaminergic stabilizer (-)-OSU6162 on mental fatigue in patients with traumatic brain injury. SETTING Single-center Neurorehabilitation Clinic. DESIGN Randomized, double-blind, placebo-controlled trial. PARTICIPANTS Sixty-four subjects with traumatic brain injury were randomized to treatment (n = 33) and placebo (n = 31). MAIN MEASURES The effects of (-)-OSU6162 at a dose of 15 mg twice a day were evaluated using self-assessment scales and neuropsychological tests measuring mental fatigue. RESULTS No difference between groups was observed on any scale at baseline. At follow-up, both groups showed significant improvement on the Fatigue Severity Scale and the Mental Fatigue Scale (both Ps < .01). Similarly, the performance of both groups increased significantly on many neuropsychological tests. However, no significant between-group difference in changes on these scales was observed before or after adjustment for confounders except for one neuropsychological test favoring the control group. Sensitivity analyses showed significantly greater changes in levels of prolactin and folic acid and heart rate (all Ps < .05) in the treatment group. The mean plasma concentration after 4 weeks of treatment was 0.14 (range, 0.01-0.32) µM, which was lower than expected. INTERPRETATION Treatment with (-)-OSU6162 had no significant effect on mental fatigue in patients with traumatic brain injury compared with placebo.