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Expert Opinion on Pharmacotherapy Apr 2024Semaglutide, a glucagon-like peptide-1 receptor agonist, is associated with significant weight loss, yet its impact on lean body mass remains insufficiently understood.... (Review)
Review
INTRODUCTION
Semaglutide, a glucagon-like peptide-1 receptor agonist, is associated with significant weight loss, yet its impact on lean body mass remains insufficiently understood. This review investigates the effect of semaglutide on lean mass in the context of obesity management.
METHODOLOGY
This study investigates through different databases (PubMed, Elsevier, and Google Scholar) from 2016 for randomized control trials (RCTs) or observational studies that assessed the use of semaglutide in overweight or obese patients, regardless of whether they have type 2 diabetes or not. The studies compared semaglutide to a placebo or alternative medications.
RESULTS
Six studies with 1,541 overweight or obese adults were included, and significant weight reductions were observed primarily due to fat mass loss. While the lean mass remained stable in some cases, notable reductions ranging from almost 0% to 40% of total weight reduction were observed in others. Noteworthy decreases in lean mass were particularly evident in larger trials, yet the proportion of lean mass relative to total body mass increased, suggesting a positive overall outcome.
CONCLUSION
Semaglutide displays potential for weight loss primarily through fat mass reduction. However, concerns arise from notable reductions in lean mass, especially in trials with a larger number of patients.
Topics: Humans; Glucagon-Like Peptides; Weight Loss; Obesity; Randomized Controlled Trials as Topic; Overweight; Glucagon-Like Peptide-1 Receptor; Anti-Obesity Agents; Diabetes Mellitus, Type 2
PubMed: 38629387
DOI: 10.1080/14656566.2024.2343092 -
Prevalence of Nausea and Vomiting in Adults Using Ropinirole: A Systematic Review and Meta-Analysis.Digestive Diseases and Sciences Mar 2018Nausea and vomiting are commonly associated with medication use. Dopaminergic agonists have been associated with these symptoms, but their impact in patients without... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nausea and vomiting are commonly associated with medication use. Dopaminergic agonists have been associated with these symptoms, but their impact in patients without Parkinson's disease, such as those with restless legs syndrome (RLS), is not well characterized.
AIMS
We sought to determine whether the non-ergoline dopamine agonist ropinirole is associated with nausea and vomiting in adults with RLS.
METHODS
We conducted a systematic review using PUBMED, EMBASE, and clinical trial databases to identify placebo-controlled clinical trials of ropinirole for RLS treatment. We extracted data including dosing schedule and the proportion of patients reporting nausea and/or vomiting. We also determined hazard ratios (HR) using a random effects proportional hazard model.
RESULTS
We extracted data from a pool of 13 studies. The prevalence of nausea in the ropinirole-treated RLS group (RLS-R; N = 1528) was 37.2% compared to 9.4% in the placebo-treated RLS group (RLS-P; N = 1395) (p < 0.0001). The prevalence of vomiting in the RLS-R group was 10.9% compared to 2.6% in the RLS-P group (p < 0.0001). Ropinirole use was associated with a higher risk of reporting nausea (HR 5.924 [4.410-7.959], p < 0.001) and experiencing vomiting (HR 4.628 [3.035-7.057], p < 0.0001). Nausea and vomiting represented nearly 50% of all adverse events reported.
CONCLUSIONS
Nausea and vomiting are quite common side effects in those using ropinirole for RLS. As RLS is more widely recognized and treated; the prevalence of ropinirole-induced nausea and vomiting could grow substantially. Ropinirole use should be considered as a cause of chronic nausea and vomiting.
Topics: Dopamine Agonists; Humans; Indoles; Nausea; Prevalence; Restless Legs Syndrome; Vomiting
PubMed: 29383607
DOI: 10.1007/s10620-018-4937-3 -
Diabetology & Metabolic Syndrome Oct 2023Glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 are the main incretin hormones, and be responsible for the insulinotropic incretin effect. The addition of... (Review)
Review
Efficacy and safety of tirzepatide, dual GLP-1/GIP receptor agonists, in the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 are the main incretin hormones, and be responsible for the insulinotropic incretin effect. The addition of a GIP agonist to a GLP-1agonist has been hypothesized to significantly potentiate the weight-losing and glycemia control effect, which might offer a new therapeutic option in the treatment of type 2 diabetes. The current meta-analysis aims to synthesize evidence of primary efficacy and safety outcomes through clinically randomized controlled trials to evaluate integrated potency and signaling properties.
METHOD
We conducted comprehensive literature searches in Cochrane Library, Web of Science, Embase and PubMed for relevant literatures investigating the efficacy and/or safety of Tirzepatide published in the English as of May 30, 2023 was retrieved. We synthesized results using standardized mean differences (SMDs) and 95% confidence intervals (95 CIs) for continuous outcomes, and odds ratios (ORs) along with 95 Cis for dichotomous outcomes. All analyses were done using Revman version 5.3, STATA version 15.1 and the statistical package 'meta'.
RESULTS
Participants treated with weekly Tirzepatide achieved HbA1c and body weight target values significantly lower than any other comparator without clinically significant increase in the incidence of hypoglycemic events, serious and all-cause fatal adverse events. However, gastrointestinal adverse events and decreased appetite events were reported more frequently with Tirzepatide treatment than with placebo/controls.
CONCLUSION
The Tirzepatide, a dual GIP/GLP-1 receptor co-agonist, for diabetes therapy has opened a new era on personalized glycemia control and weight loss in a safe manner with broad and promising clinical implications.
PubMed: 37904255
DOI: 10.1186/s13098-023-01198-4 -
European Journal of Pharmacology Nov 2023Intestinal ischemia/reperfusion injury (IRI) is a multifactorial, complex pathophysiological process in clinical settings. In recent years, intestinal IRI has received... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intestinal ischemia/reperfusion injury (IRI) is a multifactorial, complex pathophysiological process in clinical settings. In recent years, intestinal IRI has received increasing attention due to increased morbidity and mortality. To date, there are no effective treatments. Dexmedetomidine (DEX), a highly selective α-adrenergic receptor agonist, has been demonstrated to be effective against intestinal IRI. In this systematic review and meta-analysis, we evaluated the efficacy and potential mechanisms of DEX as a treatment for intestinal IRI in animal models.
METHODS
Five databases (PubMed, Embase, Web of Science, Cochrane Library, and Scopus) were searched until March 15, 2023. Using the SYRCLE risk bias tool, we assessed methodological quality. Statistical analysis was conducted using STATA 12 and R 4.2.2. We analyzed the related outcomes (mucosa damage-related indicators; inflammation-relevant markers, oxidative stress markers) relied on the fixed or random-effects models.
RESULTS
There were 15 articles including 18 studies included, and 309 animals were involved in the studies. Compared to the model groups, DEX improved intestinal IRI. DEX decreased Chiu's score and serum diamine oxidase (DAO) level. DEX reduced the level of inflammation-relevant markers (interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α). DEX also improved oxidative stress (decreased malondialdehyde (MDA), increased superoxide dismutase (SOD)).
CONCLUSIONS
DEX's effectiveness in ameliorating intestinal IRI has been demonstrated in animal models. Antioxidation, anti-inflammation, anti-apoptotic, anti-pyroptosis, anti-ferroptosis, enhancing mitophagy, reshaping the gut microbiota, and gut barrier protection are possible mechanisms. However, in light of the heterogeneity and methodological quality of these studies, further well-designed preclinical studies are warranted before clinical implication.
Topics: Rats; Animals; Dexmedetomidine; Rats, Sprague-Dawley; Adrenergic alpha-2 Receptor Agonists; Reperfusion Injury; Inflammation; Ischemia
PubMed: 37778612
DOI: 10.1016/j.ejphar.2023.176090 -
Journal of Perinatology : Official... Feb 2024Opioids and benzodiazepines have historically been employed for pain relief; however, they are associated with detrimental long-term neurodevelopmental consequences.... (Review)
Review
Opioids and benzodiazepines have historically been employed for pain relief; however, they are associated with detrimental long-term neurodevelopmental consequences. Dexmedetomidine, a highly selective alpha-2-adrenoreceptor agonist, has piqued interest as a viable alternative for neonates, owing to its potential analgesic and neuroprotective attributes. We conducted a systematic review to assess the efficacy and safety of dexmedetomidine utilization in neonates. We conducted a comprehensive search of Ovid, MEDLINE, EMBASE, PubMed, Cochrane, and CINAHL, spanning from January 2010 to September 2022. Our review encompassed six studies involving 252 neonates. Overall, dexmedetomidine may be effective in achieving sedation and analgesia. Furthermore, it may reduce the need for adjunctive sedation or analgesia, shorten the time to extubation, decrease the duration of mechanical ventilation, and accelerate the attainment of full enteral feeds. Notably, no significant adverse effects associated with dexmedetomidine were reported. Nevertheless, additional well-designed studies to establish both the efficacy and safety of dexmedetomidine in neonatal care are needed.
Topics: Infant, Newborn; Humans; Dexmedetomidine; Pain; Adrenergic alpha-2 Receptor Agonists; Pain Management; Analgesia
PubMed: 37845426
DOI: 10.1038/s41372-023-01802-5 -
Diabetes, Obesity & Metabolism Jul 2015To summarize evidence from and assess the quality of published systematic reviews evaluating the safety, efficacy and effectiveness of incretin-based medications used in... (Review)
Review
AIMS
To summarize evidence from and assess the quality of published systematic reviews evaluating the safety, efficacy and effectiveness of incretin-based medications used in the treatment of type 2 diabetes.
METHODS
We identified systematic reviews of randomized controlled trials or observational studies published in any language that evaluated the safety and/or effectiveness of glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl-peptidase-4 (DPP-4) inhibitors. Data sources used include the Cochrane Library, PubMed, EMBASE, Web of Science, International Pharmaceutical Abstracts, table of contents of diabetes journals, and hand-searching of reference lists and clinical practice guidelines. The methodological quality of systematic reviews was independently assessed by two reviewers using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist. Our study protocol was registered with PROSPERO (2013:CRD42013005149). The primary outcomes were pooled treatment effect estimates for glycaemic control, macrovascular and microvascular complications, and hypoglycaemic events.
RESULTS
We identified 467 unique citations of which 84 systematic reviews met our inclusion criteria. There were 51 reviews that evaluated GLP-1 receptor agonists and 64 reviews that evaluated DPP-4 inhibitors. The median (interquartile range) AMSTAR score was 6 (3) out of 11 for quantitative and 1 (1) for non-quantitative reviews. Among the 66 quantitative systematic reviews, there were a total of 718 pooled treatment effect estimates reported for our primary outcomes and 1012 reported pooled treatment effect estimates for secondary outcomes.
CONCLUSIONS
Clinicians and policy makers, when using the results of systematic reviews to inform decision-making with regard to round clinical care or healthcare policies for incretin-based medications, should consider the variability in quality of reviews.
Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Humans; Incretins; Observational Studies as Topic; Randomized Controlled Trials as Topic; Review Literature as Topic
PubMed: 25772666
DOI: 10.1111/dom.12465 -
Archives of Medical Research Dec 2023The increased prevalence of Impulse Control Disorders (ICDs) in dopamine agonist (DA) treated patients with Parkinson's disease is well described. Despite the frequent...
BACKGROUND
The increased prevalence of Impulse Control Disorders (ICDs) in dopamine agonist (DA) treated patients with Parkinson's disease is well described. Despite the frequent use of DAs in the management of pituitary tumors, the relationship between DAs and prevalence of ICDs in patients with pituitary tumours is unclear.
AIMS
To establish the prevalence of ICDs in patients with prolactinoma or acromegaly and determine whether prevalence differs in those on DAs to those treated without.
METHODS
Systematic review of the literature (registered a priori) reporting prevalence of ICDs in patients with prolactinoma or acromegaly (conducted June 2023). A narrative synthesis describing prevalence of ICDs according to assessment method was performed. Prevalence comparisons between patients with prolactinoma or acromegaly treated with DAs, to patients treated without, were summarised.
RESULTS
Studies were largely retrospective, observational and heterogenous, with few patients with prolactinoma and acromegaly treated without DA. Prevalence of ICDs varied between 0-60% in patients with prolactinoma, and from 5-23% in studies with at least five patients with acromegaly. In most studies comparing DA exposed to non-DA exposed cases, DA use was not associated with ICDs.
CONCLUSIONS
Reported prevalence of ICDs in patients with prolactinoma and acromegaly varies considerably. Given ICDs were reported to be highly prevalent in some studies, clinicians should be mindful of these potentially serious disorders. ICD screening tools validated for use in patients with pituitary tumors combined with prospective studies including appropriate controls, are necessary to accurately establish prevalence of ICDs and true impact of DAs in their development.
Topics: Humans; Dopamine Agonists; Pituitary Neoplasms; Prolactinoma; Acromegaly; Retrospective Studies; Prospective Studies; Disruptive, Impulse Control, and Conduct Disorders
PubMed: 37985276
DOI: 10.1016/j.arcmed.2023.102910 -
Pharmacogenomics Apr 2023To analyze roles of single nucleotide variants (SNVs) on weight loss with US FDA-approved medications. We searched the literature up until November 2022. Preferred... (Meta-Analysis)
Meta-Analysis Review
To analyze roles of single nucleotide variants (SNVs) on weight loss with US FDA-approved medications. We searched the literature up until November 2022. Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. 14 studies were included in qualitative analysis and seven in meta-analysis. SNVs in , , , , , , and were evaluated relative to weight loss with glucagon-like peptide-1 agonists (13 studies) or naltrexone-bupropion (one study). gene (rs1049353), gene (rs6923761, rs10305420), gene (rs7903146) were associated with weight loss in at least one study involving glucagon-like peptide-1 agonist(s). The meta-analysis did not identify any consistent effect of SNVs. Pharmacogenetic interactions for exenatide, liraglutide, naltrexone-bupropion and weight loss were identified, but the directionality was inconsistent.
Topics: Adult; Humans; Hypoglycemic Agents; Pharmacogenetics; Naltrexone; Bupropion; Peptides; Venoms; Glucagon-Like Peptide 1; Weight Loss; Glucagon-Like Peptide-1 Receptor; Diabetes Mellitus, Type 2; Protein Serine-Threonine Kinases
PubMed: 36999540
DOI: 10.2217/pgs-2022-0192 -
Frontiers in Endocrinology 2023Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA). At present, there is no controversy...
AIMS
Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA). At present, there is no controversy over its effectiveness, but its safety. We conducted a systematic review to assess the safety of tirzepatide.
METHODS
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias. The systematic review was conducted Revman5.4.
RESULTS
Nine RCTs with a total of 9818 patients were included. The overall safety profile of tirzepatide is similar to GLP-1RAs, except for the hypoglycemia (tirzepatide 15mg, pooled RR=3.83, 95% CI [1.19- 12.30], ) and discontinuation (tirzepatide 10mg, pooled RR=1.75,95%CI[1.16-2.63], and 15mg, pooled RR=2.03, 95%CI [1.37-3.01], ). It also showed that the dose escalation could not rise the occurrence rates of total, severe, gastrointestinal adverse events and hypoglycemia (); Compared with 5mg, tirzepatide 10mg and 15mg were associated with more frequent nausea (), discontinuation () and injection-site reaction (); The rates of vomiting and diarrhea were dose-dependence at the range of 5-15mg.
CONCLUSION
The safety profile of tirzepatide is generally acceptable, similar to GLP-1 RAs. It is necessary to pay attention to its specific adverse events (hypoglycemia and discontinuation) at high doses (10mg or higher). Nausea, vomiting, diarrhea, discontinuation and injection-site reaction were dose-dependence among specific dose ranges.As the heterogeneity in different studies by interventions, the results may be with biases and the further confirmation is needed. Meanwhile, more well-designed trials are needed to control the confounding factors and ensure adequate sample size.
Topics: Humans; Diabetes Mellitus, Type 2; Diarrhea; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Hypoglycemia; Hypoglycemic Agents; Nausea; Vomiting
PubMed: 37051199
DOI: 10.3389/fendo.2023.1121387 -
Journal of Neurophysiology Aug 2023Spinal motoneurons contain many ion channels and receptors upon which various cannabinoids are known to act. This scoping review involved the synthesis of evidence from... (Review)
Review
Spinal motoneurons contain many ion channels and receptors upon which various cannabinoids are known to act. This scoping review involved the synthesis of evidence from literature published before August 2022 about the effects of cannabinoids on quantifiable measures of motoneuron output. Four databases (MEDLINE, Embase, PsycINFO, and Web of Science CoreCollection) were queried and 4,237 unique articles were retrieved. Twenty-three studies met the inclusion criteria, and the findings from these studies were grouped according to four emergent themes: rhythmic motoneuron output, afferent feedback integration, membrane excitability, and neuromuscular junction transmission. This synthesis of evidence suggests that CB1 agonists can increase the frequency of cyclical patterns of motoneuron output (i.e., fictive locomotion). Furthermore, a majority of the evidence indicates that activating CB1 receptors at motoneuron synapses promotes excitation of motoneurons by enhancing excitatory synaptic transmission and depressing inhibitory synaptic transmission. The collated study results reveal variable effects of cannabinoids on acetylcholine release at the neuromuscular junction, and the influence of cannabinoids in this area requires more work to ensure precision of findings for CB1 agonist and antagonist impact. Altogether, these reports indicate that the endocannabinoid system is integral within the final common pathway and can impact motor output. This review contributes to understanding the effects of endocannabinoids on synaptic integration at the motoneuron and modulation of motor output.
Topics: Cannabinoids; Motor Neurons; Synapses; Synaptic Transmission; Neuromuscular Junction
PubMed: 37283484
DOI: 10.1152/jn.00460.2022