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The American Journal of Clinical... Sep 2023Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are new drugs for the treatment of obesity. (Meta-Analysis)
Meta-Analysis
The Weight-loss Effect of GLP-1RAs Glucagon-Like Peptide-1 Receptor Agonists in Non-diabetic Individuals with Overweight or Obesity: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials.
BACKGROUND
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are new drugs for the treatment of obesity.
OBJECTIVE
To assess the weight-loss effects of GLP-1RAs in the treatment of patients with overweight or obesity without diabetes.
METHODS
This is a systematic review with meta-analysis and trial sequential analysis. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from their inception to January 1, 2022. Eligible trials report on outcomes including body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), or total body fat (TBF). Mean differences (MDs) and standardized mean differences (SMDs) were summarized using random-effects models.
RESULTS
Forty-one trials involving 15,135 participants were included. Compared with controls, GLP-1RAs significantly reduced BW (MD -5.319 kg, 95% CI: -6.465, -4.174), BMI (MD -2.373 kg/m, 95% CI: -2.821, -1.924), WC (MD -4.302 cm, CI:-5.185 to -3.419), WHR (MD -0.011, CI -0.015 to -0.007), but not TBF (MD -0.320%, CI -1.420 to -0.780). Trial sequential analysis (TSA) supported conclusive evidence of the effects of GLP-1RAs on BW, BMI, and WC for weight loss. GLP-1RAs had nonlinear dose-response relationships with weight loss. Extensive sensitivity analyses demonstrated the robustness of the results, though the GRADE certainty of the evidence ranged from high to very low. High to moderate GRADE certainty of evidence suggested semaglutide as the most effective GLP-1RA agent, with the best efficacy and low to moderate risk of adverse effects.
CONCLUSIONS
The present study provides conclusive evidence for the effect of GLP-1RAs on weight loss in a nonlinear dose-response manner in patients with obesity or overweight without diabetes. In terms of changes in BW, BMI, and WC, there is firm evidence for the overall weight-loss effects of GLP-1RAs. Of the GLP-1RAs, semaglutide might be the most effective agent.
Topics: Humans; Overweight; Glucagon-Like Peptide-1 Receptor; Randomized Controlled Trials as Topic; Obesity; Body Weight; Weight Loss
PubMed: 37661106
DOI: 10.1016/j.ajcnut.2023.04.017 -
European Journal of Anaesthesiology Oct 2023Pain after craniotomy can be intense and its management is often suboptimal.
BACKGROUND
Pain after craniotomy can be intense and its management is often suboptimal.
OBJECTIVES
We aimed to evaluate the available literature and develop recommendations for optimal pain management after craniotomy.
DESIGN
A systematic review using procedure-specific postoperative pain management (PROSPECT) methodology was undertaken.
DATA SOURCES
Randomised controlled trials and systematic reviews published in English from 1 January 2010 to 30 June 2021 assessing pain after craniotomy using analgesic, anaesthetic or surgical interventions were identified from MEDLINE, Embase and Cochrane Databases.
ELIGIBILITY CRITERIA
Each randomised controlled trial (RCT) and systematic review was critically evaluated and included only if met the PROSPECT requirements. Included studies were evaluated for clinically relevant differences in pain scores, use of nonopioid analgesics, such as paracetamol and NSAIDs, and current clinical relevance.
RESULTS
Out of 126 eligible studies identified, 53 RCTs and seven systematic review or meta-analyses met the inclusion criteria. Pre-operative and intra-operative interventions that improved postoperative pain were paracetamol, NSAIDs, intravenous dexmedetomidine infusion, regional analgesia techniques, including incision-site infiltration, scalp nerve block and acupuncture. Limited evidence was found for flupirtine, intra-operative magnesium sulphate infusion, intra-operative lidocaine infusion, infiltration adjuvants (hyaluronidase, dexamethasone and α-adrenergic agonist added to local anaesthetic solution). No evidence was found for metamizole, postoperative subcutaneous sumatriptan, pre-operative oral vitamin D, bilateral maxillary block or superficial cervical plexus block.
CONCLUSIONS
The analgesic regimen for craniotomy should include paracetamol, NSAIDs, intravenous dexmedetomidine infusion and a regional analgesic technique (either incision-site infiltration or scalp nerve block), with opioids as rescue analgesics. Further RCTs are required to confirm the influence of the recommended analgesic regimen on postoperative pain relief.
Topics: Humans; Pain Management; Dexmedetomidine; Acetaminophen; Analgesics; Pain, Postoperative; Craniotomy; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37417808
DOI: 10.1097/EJA.0000000000001877 -
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 -
MedRxiv : the Preprint Server For... Sep 2023Beta-cell monogenic forms of diabetes are the area of diabetes care with the strongest support for precision medicine. We reviewed treatment of hyperglycemia in...
BACKGROUND
Beta-cell monogenic forms of diabetes are the area of diabetes care with the strongest support for precision medicine. We reviewed treatment of hyperglycemia in GCK-related hyperglycemia, HNF1A-HNF4A- and HNF1B-diabetes, Mitochondrial diabetes (MD) due to m.3243A>G variant, 6q24-transient neonatal diabetes (TND) and SLC19A2-diabetes.
METHODS
Systematic reviews with data from PubMed, MEDLINE and Embase were performed for the different subtypes. Individual and group level data was extracted for glycemic outcomes in individuals with genetically confirmed monogenic diabetes.
RESULTS
147 studies met inclusion criteria with only six experimental studies and the rest being single case reports or cohort studies. Most studies had moderate or serious risk of bias.For GCK-related hyperglycemia, six studies (N=35) showed no deterioration in HbA1c on discontinuing glucose lowering therapy. A randomized trial (n=18 per group) showed that sulfonylureas (SU) were more effective in HNF1A-diabetes than in type 2 diabetes, and cohort and case studies supported SU effectiveness in lowering HbA1c. Two crossover trials (n=15 and n=16) suggested glinides and GLP-1 receptor agonists might be used in place of SU. Evidence for HNF4A-diabetes was limited. While some patients with HNF1B-diabetes (n=301) and MD (n=250) were treated with oral agents, most were on insulin. There was some support for the use of oral agents after relapse in 6q24-TND, and for thiamine improving glycemic control and reducing insulin requirement in SLC19A2-diabetes (less than half achieved insulin-independency).
CONCLUSION
There is limited evidence to guide the treatment in monogenic diabetes with most studies being non-randomized and small. The data supports: no treatment in GCK-related hyperglycemia; SU for HNF1A-diabetes. Further evidence is needed to examine the optimum treatment in monogenic subtypes.
PubMed: 37214872
DOI: 10.1101/2023.05.12.23289807 -
Women's Health (London, England) 2024Polycystic ovary syndrome is a common reproductive endocrine condition that affects women of fertile age and is characterized by three main features, including... (Review)
Review
Polycystic ovary syndrome is a common reproductive endocrine condition that affects women of fertile age and is characterized by three main features, including hyperandrogenism, chronic anovulation, and polycystic ovaries. In addition, half of women with polycystic ovary syndrome have insulin resistance, and obesity or overweight, type 2 diabetes, hypertension, and hyperlipidemia are the most common metabolic abnormalities affecting (30%) women with polycystic ovary syndrome. Weight loss is regarded as the first-line treatment as it can potentially improve polycystic ovary syndrome parameters (androgen levels, menstrual cyclicity, lipid and glucose metabolism). However, achieving and maintaining weight loss can be challenging, and pharmacological agents could be essential to achieve optimal glycemic control and improve the endocrine disturbance associated with polycystic ovary syndrome. Glucagon-like peptide-1 receptor agonist has been demonstrated as monotherapy or in combination with metformin for managing obesity and insulin resistance associated with polycystic ovary syndrome. Yet, its effect on endocrine and metabolic parameters remains elusive, and further research is needed to close the gap. The aim is to evaluate the efficacy of glucagon-like peptide-1 receptor agonist monotherapy and/or a combined treatment between glucagon-like peptide-1 receptor agonist and metformin for improving anthropometric measurements, endocrine and metabolic parameters in lean and obese women with polycystic ovary syndrome. A systematic review of longitudinal cohort studies was conducted across databases including Ovid Medline, PubMed Central, and Cochrane Library between 2015 and 2022. Eligible studies included participants with polycystic ovary syndrome diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health criteria. A total of eight studies including 486 patients with polycystic ovary syndrome were analyzed. The mean age was between 18 and 45 years with mean follow-up period between 12 and 32 weeks. In all these studies, results were comparable for the reduction in body mass index, waist circumference, fat mass, and visceral fat mass; however, it was more in combination therapy versus comparator. In conclusion, glucagon-like peptide-1 receptor agonists effectively reduce body weight and improve some of the endocrine and metabolic parameters of polycystic ovary syndrome. A combined treatment with glucagon-like peptide-1 receptor agonist and metformin had significant effects on weight loss and favorable results on endocrine and metabolic parameters, yet further research is needed to discover the long-term safety of combined therapy in women diagnosed with polycystic ovary syndrome and obesity or overweight.
Topics: Female; Humans; Infant; Male; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor Agonists; Insulin Resistance; Longitudinal Studies; Metformin; Obesity; Overweight; Polycystic Ovary Syndrome; United States; Weight Loss
PubMed: 38444070
DOI: 10.1177/17455057241234530 -
Pituitary Oct 2023Giant prolactinomas are a rare entity, representing approximately 5% of all prolactinomas. A systematic review of 196 adult cases was performed. A comparison of the... (Review)
Review
PURPOSE
Giant prolactinomas are a rare entity, representing approximately 5% of all prolactinomas. A systematic review of 196 adult cases was performed. A comparison of the clinical, biochemical and radiological characteristics, management and therapeutic outcomes in men versus women is made.
METHODS
A structured search was conducted using the term 'giant prolactinoma'. Following inclusion criteria were used: diameter ≥ 40 mm, prolactin levels > 1000 ng/ml and no concomitant GH/ ACTH secretion.
RESULTS
196 cases were included [age: 38 (28-50) years, F/M ratio: 1/3.6]. Median tumor diameter was 53 (43-69) mm. Pituitary deficiency was present in 91% of cases, with hypogonadotropic hypogonadism being the most frequent. Most common presenting symptoms were visual impairment (73%) and headache (50%) in men and amenorrhea (58%) in women. 82% of cases were treated with a dopamine agonist (DA) as first-line treatment which led to normoprolactinemia, tumor shrinkage and visual improvement in 51%, 88% and 85% of cases, respectively. Surgery was performed in 29% of cases and all showed tumor remnant and persistent hyperprolactinemia. Women had a lower prolactin level and a smaller tumor diameter at diagnosis but pituitary deficiencies were more frequent and outcome was worse.
CONCLUSION
Giant prolactinomas are rare and have a male predominance. Visual impairment is the most frequent presenting symptom in men and amenorrhea in women. The gender-related difference in tumor size and level of prolactin was confirmed in this analysis where men had a larger diameter and a higher baseline prolactin level. DAs are the treatment of choice, irrespective of tumor size and presence of visual impairment. As only half of the cases achieved normoprolactinemia we do not, in contrast to previous literature, state giant prolactinomas to be exquisitely sensitive to DAs. Patient characteristics associated with persistent hyperprolactinemia after treatment with a DA were female gender, higher baseline prolactin and larger tumor size . This analysis did show TSH- and ACTH-deficiency to be more frequent after surgery which was not seen for LH/FSH deficiency.
Topics: Female; Adult; Male; Humans; Prolactinoma; Pituitary Neoplasms; Hyperprolactinemia; Prolactin; Amenorrhea; Dopamine Agonists; Hypopituitarism; Vision Disorders; Adrenocorticotropic Hormone
PubMed: 37544978
DOI: 10.1007/s11102-023-01337-0 -
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 -
Clinical Therapeutics Aug 2023Tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide 1 receptor agonist, has been approved by the US Food and Drug Administration for... (Meta-Analysis)
Meta-Analysis Review
Effect of the Dual Glucose‐Dependent Insulinotropic Peptide/Gulcagon‐like Peptide 1 Receptor Agonist Tirzepatide on Lipid Profile and Waist Circumference: A Systematic Review and Meta‐analysis.
PURPOSE
Tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide 1 receptor agonist, has been approved by the US Food and Drug Administration for the treatment of type 2 diabetes. The purpose of this meta-analysis is to evaluate the impact of tirzepatide on lipid profile and waist circumference (WC), both of which are risk factors of cardiovascular diseases.
METHODS
The PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were systematically searched for articles published from database inception to July 31, 2022. This meta-analysis included 7 randomized controlled trials with a minimum duration of 12 weeks that compared tirzepatide with placebo or other antidiabetic medications. The random-effects model was used to estimate mean differences in lipid profile and WC from baseline. The Cochrane risk-of-bias tool for randomized trials, version 2 was used to assess the outcome's risk of bias. We evaluated the evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.
FINDINGS
A total of 8 articles from 7 trials with 7151 participants were included. All 3 eligible maintenance doses of tirzepatide (5, 10, and 15 mg once a week) were effective in increasing total cholesterol (TC) (P < 0.05), HDL-C (P < 0.05), VLDL-C (P < 0.01), triglyceride (TG) (P < 0.01), and WC (P < 0.01) changes from baseline compared with control agents including placebo, semaglutide, dulaglutide, and degludec. Although the evidence for VLDL-C and TGs by GRADE were high or moderate, the evidences for TC, HDL-C, and WC were low or moderate. Only 5mg once-weekly tirzepatide (P < 0.05), not 10 or 15 mg, could induce significant alteration in LDL-C before sensitivity analysis. The evidence by GRADE was moderate.
IMPLICATIONS
Tirzepatide had superiority over placebo or other antidiabetic agents in controlling lipid and WC levels. However, the levels of evidence by GRADE varied greatly across different outcome indicators. Limitations of the study include evaluating secondary outcomes of original trials for the meta-analyses, not assessing the effect of baseline lipid-lowering therapy on lipid levels, and not exploring the bias induced by glycemic improvement and weight loss.
Topics: Humans; Gastric Inhibitory Polypeptide; Diabetes Mellitus, Type 2; Waist Circumference; Peptides; Hypoglycemic Agents; Lipids; Glucagon-Like Peptide-1 Receptor
PubMed: 37455226
DOI: 10.1016/j.clinthera.2023.06.008 -
Diabetology & Metabolic Syndrome Nov 2023Diabetes is a complicated, chronic condition that requires ongoing medical attention as well as multiple risk-reduction measures beyond glucose control. The prevalence... (Review)
Review
BACKGROUND
Diabetes is a complicated, chronic condition that requires ongoing medical attention as well as multiple risk-reduction measures beyond glucose control. The prevalence of chronic kidney disease (CKD) is highly variable in different parts of the world due to various environmental, ethnic, socioeconomic, and rural-urban differences. Diabetes is the leading cause of CKD. This study aimed to estimate the global prevalence of CKD and its associated factors among type 2 diabetes(T2DM) patients, provide scientific evidence for a better understanding of the burden of CKD among diabetes mellitus type 2 patients, and design interventional strategies.
METHODS
Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist guideline was followed for this review and meta-analysis. The electronic databases (Pub Med, Cochrane Library, Google Scholar, and grey literature) were searched to retrieve articles by using keywords. Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument was used to assess the quality of studies. The meta-analysis was conducted using STATA 17 software. The Meta logistic regression was computed to present the pooled prevalence and Odds ratio (OR) of the determinate factors with a 95% confidence interval (CI).
RESULTS
In this systematic review and meta-analysis 20 studies were done in 13 different countries. The pooled magnitude of chronic kidney disease among type 2 DM patients was 27% (95% CI 21%, 33%). The prevalence of chronic kidney disease differs across countries, with the maximum in the USA and the lowest in the United Arab Emirates. Patients with CKD have an elevated risk of severe renal and cardiovascular morbidity and mortality. Renin-angiotensin system inhibitors, sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide 1 receptor agonists, and, more recently, non-steroidal mineralocorticoid receptor antagonists are among the medications that have been demonstrated to slow the progression of CKD. In this systematic review and meta-analysis increased age, obesity, having a history of type 2 diabetes mellitus, smoking history, presence of hypertension, and cardiac heart disease were factors significantly associated with the presence of chronic kidney disease among type 2 diabetic patients.
CONCLUSIONS
The prevalence of chronic kidney disease among type 2 diabetes mellitus patients was high based on the included 20 articles. The review reported that old age, hypertension, cardiac disease, smoking, obesity, and duration of diabetes mellitus was predictor variable for chronic kidney disease among type 2 diabetic patients. Therefore, in order to lower the morbidity and mortality from chronic kidney disease among type 2 diabetic patients, it is advised to develop both preventive and curative intervention strategies, such as raising awareness, creating a supportive environment, and prescribing appropriate medication at an early stage.
PubMed: 38012781
DOI: 10.1186/s13098-023-01202-x -
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