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Hormone and Metabolic Research =... Nov 2017Gut hormones are known to play an important role in long-term weight loss maintenance after bariatric surgery. However, the interplay between gut hormones and... (Meta-Analysis)
Meta-Analysis Review
Gut hormones are known to play an important role in long-term weight loss maintenance after bariatric surgery. However, the interplay between gut hormones and diet-induced weight changes remains unclear. Our aims were to evaluate the alterations of gut hormones in diet-induced weight loss, weight maintenance, and weight regain periods. Available studies were searched on MEDLINE, EMASE, ClinicalTrials.gov, the Cochrane Library, and Web of science from inception to October 2016. After selection, 16 studies with 656 participants were included. Based on current evidence, we found significant alterations of gut hormones induced by different diets. In weight-loss diets, decreased fasting total PYY, GLP-1, CCK, GIP, PP, and amylin along with increased ghrelin levels were observed in most studies. After weight loss, the persistent decreases of fasting total PYY and GLP-1 levels as well as increased appetite were reported, suggesting the profound impact of altered gut hormones on later weight regain after dietary intervention. The differences between diet-induced changes in gut hormones and other treatments such as bariatric surgery and exercise are also discussed in this review. Although significant alterations of gut hormones were found during weight changes, huge heterogeneity exists in methods and populations. More large-scale studies with elaborate design addressing the gut hormone alterations in dietary weight regulation are required in the future.
Topics: Diet, Carbohydrate-Restricted; Diet, High-Protein; Diet, Reducing; Gastrointestinal Hormones; Humans; Quality Assurance, Health Care; Weight Loss
PubMed: 28934819
DOI: 10.1055/s-0043-115646 -
The Cochrane Database of Systematic... Mar 2014Cisplatin and several related antineoplastic drugs used to treat many types of solid tumours are neurotoxic, and most patients completing a full course of cisplatin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cisplatin and several related antineoplastic drugs used to treat many types of solid tumours are neurotoxic, and most patients completing a full course of cisplatin chemotherapy develop a clinically detectable sensory neuropathy. Effective neuroprotective therapies have been sought.
OBJECTIVES
To examine the efficacy and safety of purported chemoprotective agents to prevent or limit the neurotoxicity of cisplatin and related drugs.
SEARCH METHODS
On 4 March 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and CINAHL Plus for randomised trials designed to evaluate neuroprotective agents used to prevent or limit neurotoxicity of cisplatin and related drugs among human patients.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) or quasi-RCTs in which the participants received chemotherapy with cisplatin or related compounds, with a potential chemoprotectant (acetylcysteine, amifostine, adrenocorticotrophic hormone (ACTH), BNP7787, calcium and magnesium (Ca/Mg), diethyldithiocarbamate (DDTC), glutathione, Org 2766, oxcarbazepine, or vitamin E) compared to placebo, no treatment, or other treatments. We considered trials in which participants underwent evaluation zero to six months after completing chemotherapy using quantitative sensory testing (the primary outcome) or other measures including nerve conduction studies or neurological impairment rating using validated scales (secondary outcomes).
DATA COLLECTION AND ANALYSIS
Two review authors assessed each study, extracted the data and reached consensus, according to standard Cochrane methodology.
MAIN RESULTS
As of 2013, the review includes 29 studies describing nine possible chemoprotective agents, as well as description of two published meta-analyses. Among these trials, there were sufficient data in some instances to combine the results from different studies, most often using data from secondary non-quantitative measures. Nine of the studies were newly included at this update. Few of the included studies were at a high risk of bias overall, although often there was too little information to make an assessment. At least two review authors performed a formal review of an additional 44 articles but we did not include them in the final review for a variety of reasons.Of seven eligible amifostine trials (743 participants in total), one used quantitative sensory testing (vibration perception threshold) and demonstrated a favourable outcome in terms of amifostine neuroprotection, but the vibration perception threshold result was based on data from only 14 participants receiving amifostine who completed the post-treatment evaluation and should be regarded with caution. Furthermore the change measured was subclinical. None of the three eligible Ca/Mg trials (or four trials if a single retrospective study was included) described our primary outcome measures. The four Ca/Mg trials included a total of 886 participants. Of the seven eligible glutathione trials (387 participants), one used quantitative sensory testing but reported only qualitative analyses. Four eligible Org 2766 trials (311 participants) employed quantitative sensory testing but reported disparate results; meta-analyses of three of these trials using comparable measures showed no significant vibration perception threshold neuroprotection. The remaining trial reported only descriptive analyses. Similarly, none of the three eligible vitamin E trials (246 participants) reported quantitative sensory testing. The eligible single trials involving acetylcysteine (14 participants), diethyldithiocarbamate (195 participants), oxcarbazepine (32 participants), and retinoic acid (92 participants) did not perform quantitative sensory testing. In all, this review includes data from 2906 participants. However, only seven trials reported data for the primary outcome measure of this review, (quantitative sensory testing) and only nine trials reported our objective secondary measure, nerve conduction test results. Additionally, methodological heterogeneity precluded pooling of the results in most cases. Nonetheless, a larger number of trials reported the results of secondary (non-quantitative and subjective) measures such as the National Cancer Institute Common Toxicity Criteria (NCI-CTC) for neuropathy (15 trials), and these results we pooled and reported as meta-analysis. Amifostine showed a significantly reduced risk of developing neurotoxicity NCI-CTC (or equivalent) ≥ 2 compared to placebo (RR 0.26, 95% CI 0.11 to 0.61). Glutathione was also efficacious with an RR of 0.29 (95% CI 0.10 to 0.85). In three vitamin E studies subjective measures not suitable for combination in meta analysis each favoured vitamin E. For other interventions the qualitative toxicity measures were either negative (N-acetyl cysteine, Ca/Mg, DDTC and retinoic acid) or not evaluated (oxcarbazepine and Org 2766).Adverse events were infrequent or not reported for most interventions. Amifostine was associated with transient hypotension in 8% to 62% of participants, retinoic acid with hypocalcaemia in 11%, and approximately 20% of participantss withdrew from treatment with DDTC because of toxicity.
AUTHORS' CONCLUSIONS
At present, the data are insufficient to conclude that any of the purported chemoprotective agents (acetylcysteine, amifostine, calcium and magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxcarbazepine, retinoic acid, or vitamin E) prevent or limit the neurotoxicity of platin drugs among human patients, as determined using quantitative, objective measures of neuropathy. Amifostine, calcium and magnesium, glutathione, and vitamin E showed modest but promising (borderline statistically significant) results favouring their ability to reduce the neurotoxicity of cisplatin and related chemotherapies, as measured using secondary, non-quantitative and subjective measures such as the NCI-CTC neuropathy grading scale. Among these interventions, the efficacy of only vitamin E was evaluated using quantitative nerve conduction studies; the results were negative and did not support the positive findings based on the qualitative measures. In summary, the present studies are limited by the small number of participants receiving any particular agent, a lack of objective measures of neuropathy, and differing results among similar trials, which make it impossible to conclude that any of the neuroprotective agents tested prevent or limit the neurotoxicity of platinum drugs.
Topics: Antineoplastic Agents; Cisplatin; Humans; Neuroprotective Agents; Peptide Fragments; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic
PubMed: 24687190
DOI: 10.1002/14651858.CD005228.pub4 -
Diabetes, Obesity & Metabolism May 2012The objective of this systematic review was to assess the published literature on the effectiveness of exenatide twice daily (exenatide) in clinical practice,... (Review)
Review
The objective of this systematic review was to assess the published literature on the effectiveness of exenatide twice daily (exenatide) in clinical practice, specifically its effects on haemoglobin A1c (A1C), fasting glucose (FG), weight, systolic blood pressure (SBP), medication use, hospitalization and cardiovascular disease (CVD) outcomes. A systematic literature search using the MEDLINE database of English language literature published between January 2005 and May 2011 was performed. The review included retrospective or prospective observational studies that included 100 or more patients per treatment group. A total of 15 studies meeting the inclusion criteria were identified. The studies revealed significant reductions of -0.4 to -0.9% in A1C, -10 mg/dl in FG, -2 to -11 kg in body weight and -2 to -11 mmHg in SBP. Statistically significant reductions in the use or dosage of either oral glucose-lowering medications or insulin after initiating exenatide treatment were found in every observational study that assessed medication changes, including reductions in dosage of up to 75% in sulphonylureas dosages, 22% in metformin, 66% in thiazolidinediones (TZD) or TZD combination therapy and 75% in prandial insulin. Exenatide-treated patients experienced significantly lower rates of all-cause and CVD-related hospitalization and CVD events than patients treated with other therapies overall. In this review of observational studies, exenatide initiation was associated with significant reductions in clinically relevant outcomes. Improvements in A1C, FG, weight and SBP in the observational studies in this review were consistent with improvements observed in controlled clinical trials.
Topics: Blood Glucose; Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exenatide; Female; Glycated Hemoglobin; Hospitalization; Humans; Hypoglycemic Agents; Male; Peptides; United States; Venoms; Weight Loss
PubMed: 22074017
DOI: 10.1111/j.1463-1326.2011.01533.x -
Clinical Therapeutics May 2011Glucose homeostasis is the result of a complex interaction of a spectrum of hormones, including insulin, glucagon, amylin, and the incretins. Incretins are released by... (Review)
Review
BACKGROUND
Glucose homeostasis is the result of a complex interaction of a spectrum of hormones, including insulin, glucagon, amylin, and the incretins. Incretins are released by enteroendocrine cells in the intestine in response to a meal. Incretin dysfunction, along with a number of other defects, has been implicated in contributing to the pathogenesis of type 2 diabetes mellitus (T2DM). Therapies that restore incretin activity may reduce the pathophysiologic consequences of diabetes.
OBJECTIVES
The aim of this article was to review incretin physiology and studies of incretin therapy with glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors that were developed to specifically address the blunted incretin response in patients with T2DM.
METHODS
Relevant English-language publications between 1995 and 2010 were identified through a search of the MEDLINE and EMBASE databases using the search terms incretin, type 2 diabetes mellitus, GLP-1, glucose-dependent insulinotropic polypeptide, and DPP-4. Review articles and preclinical and clinical trials that described relevant details of the epidemiology of diabetes and incretin physiology in health and in T2DM were selected for review and inclusion. Clinical trials were used to describe the clinical efficacy and safety of the GLP-1 receptor agonists and DPP-4 inhibitors in patients with T2DM. An occasional systematic review article and/or meta-analysis summarizing numerous clinical trials of a particular agent was selected for summarizing key data.
RESULTS
Pharmacologic modulation of incretin pathophysiology by GLP-1 receptor agonists and DPP-4 inhibitors significantly improved glycemic control, benefited β-cell function, improved dyslipidemia, and lowered the risk of hypoglycemia compared with insulin and sulfonylureas. Unlike the DPP-4 inhibitors, GLP-1 receptor agonist therapy also produced weight loss, an important consideration given the close association among T2DM, overweight/obesity, and cardiovascular disease. The most common adverse events with GLP-1 receptor agonist therapy included nausea (28%-44%), vomiting (13%-17%), and diarrhea (11%-17%), which generally reduced in incidence and severity with continued therapy. The tolerability profile of the DPP-4 inhibitors was very good, with the incidence of adverse events similar to that of placebo. There was a suggestion of an increased incidence of nasopharyngitis versus placebo (5%-6% vs 3%-4%) with sitagliptin and urinary tract infection (6.8% vs 6.1% with placebo) and headache with saxagliptin (6.5% vs 5.9% with placebo).
CONCLUSION
The 2 incretin drug classes provided effective and consistent glycemic control with a good tolerability profile. These agents might also improve long-term β-cell function and either reduce body weight or be weight neutral. Their role in the therapeutic armamentarium of T2DM is evolving as their potential strengths and weaknesses become better defined.
Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Incretins
PubMed: 21665040
DOI: 10.1016/j.clinthera.2011.04.015 -
Diabetes, Obesity & Metabolism Feb 2011the objective of this systematic review and meta-analysis was to assess the effect of pramlintide on glycemic control, weight and incidence of nausea and hypoglycaemia... (Meta-Analysis)
Meta-Analysis Review
The effect of pramlintide acetate on glycemic control and weight in patients with type 2 diabetes mellitus and in obese patients without diabetes: a systematic review and meta-analysis.
AIM
the objective of this systematic review and meta-analysis was to assess the effect of pramlintide on glycemic control, weight and incidence of nausea and hypoglycaemia in patients with type 2 diabetes mellitus (T2DM) and in obese patients without diabetes (OBP).
METHODS
eight randomized, clinical trials were identified from multiple databases. Qualitative assessments and quantitative analyses were performed.
RESULTS
in four T2DM studies (N = 930,duration of studies 16-52 weeks,120-150 mcg/dose BID-TID), all patients received insulin therapy. In four obesity studies (N = 686,duration of studies 6-24 weeks,120-360 mcg/dose BID-TID), equivalent volumes of placebo were administered before major meals. Pramlintide significantly reduced haemoglobin A1c (HbA1c) (-0.33% [95% CI -0.51, -0.14], p = 0.004) and weight (-2.57 kg, [95% CI -3.44, -1.70], p < 0.00001) versus the control group. More patients in the control group reported hypoglycaemia of any severity versus the pramlintide group (risk ratio 0.84 [95% CI 0.69, 10.3], p = 0.09). In OBP, pramlintide caused a reduction in weight (-2.27 kg [95% CI -2.88, -1.66], p < 0.00001). When event data from both populations were combined, patients randomized to pramlintide were 1.8 times more likely to report nausea of any severity versus control (p = 0.0005).
CONCLUSIONS
pramlintide was associated with a small reduction in HbA1c, and a modest reduction in weight in patients with T2DM or OBP. There was increased incidence of nausea but not hypoglycaemia at any time during therapy. Studies about the long-term effect of pramlintide on diabetes- and cardiovascular-related complications and cost-effectiveness analyses are needed.
Topics: Body Weight; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Incidence; Islet Amyloid Polypeptide; Male; Obesity; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 21199269
DOI: 10.1111/j.1463-1326.2010.01337.x