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Annals of Internal Medicine May 2024Yao H, Zhang A, Li D, et al. BMJ. 2024;384:e076410. 38286487. (Meta-Analysis)
Meta-Analysis
Yao H, Zhang A, Li D, et al. BMJ. 2024;384:e076410. 38286487.
Topics: Diabetes Mellitus, Type 2; Humans; Glucagon-Like Peptide-1 Receptor; Hypoglycemic Agents; Body Weight; Blood Glucose
PubMed: 38710089
DOI: 10.7326/J24-0028 -
Cureus Apr 2024The objective of the study is mentioned, but it could be further clarified by explicitly stating the aim to compare the effectiveness and safety of direct oral... (Review)
Review
Comparison of Effectiveness and Safety of Direct-Acting Oral Anticoagulants and Vitamin K Agonists in Patients With Atrial Fibrillation and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.
The objective of the study is mentioned, but it could be further clarified by explicitly stating the aim to compare the effectiveness and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) specifically in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD). We conducted a thorough electronic search of the literature, encompassing databases such as PubMed, EMBASE, Cochrane Library, and Web of Science from their inception up to March 5, 2024. Furthermore, we meticulously examined the bibliographies of included studies to identify additional relevant literature. The reporting of this meta-analysis adhered to the guidelines outlined in the Preferred Reporting of Systematic Review and Meta-analysis guidelines. The endpoints evaluated in this meta-analysis included all-cause mortality, stroke or systemic embolism, and major bleeding. Data analysis was carried out utilizing RevMan Version 5.4 (Cochrane, London, United Kingdom). Dichotomous outcomes, including all-cause mortality, stroke or systemic embolism, and major bleeding, were presented as risk ratios (RRs) with corresponding 95% confidence intervals (CI). A total of 11 studies were incorporated in this meta-analysis, comprising a pooled sample size of 44,863 participants with AF. The pooled analysis revealed no significant disparity between DOACs and VKAs concerning stroke or systemic embolism (RR: 0.93, 95% CI: 0.77 to 1.14) and all-cause mortality (RR: 0.86, 95% CI: 0.74 to 1.00). However, there was a noteworthy reduction in the risk of major bleeding events associated with DOACs compared to VKAs (RR: 0.84, 95% CI: 0.73 to 0.96). Consequently, DOACs may be considered a viable alternative to warfarin in patients with ESRD. However, we need further larger clinical trials to validate these findings.
PubMed: 38699102
DOI: 10.7759/cureus.57447 -
Endocrine Practice : Official Journal... May 2024Resmetirom, a liver-directed, thyroid hormone receptor beta-selective agonist, has recently been approved to treat nonalcoholic steatohepatitis (NASH). This...
BACKGROUND
Resmetirom, a liver-directed, thyroid hormone receptor beta-selective agonist, has recently been approved to treat nonalcoholic steatohepatitis (NASH). This meta-analysis aimed to summarize the efficiency and safety of resmetirom in treating NASH.
METHODS
Electronic databases were searched for randomized controlled trials (RCTs) of resmetirom vs placebo in patients with NASH. The primary outcomes were the changes from baseline in hepatic fat content, liver histology, including NASH resolution, and noninvasive markers of hepatic fibrosis.
RESULTS
Three randomized controlled trials (n = 2231) met the inclusion criteria. Compared to placebo, resmetirom achieved greater reductions from baseline in hepatic fat content assessed by magnetic resonance imaging proton density fat fraction (for resmetirom 80 mg: MD -27.76% [95%CI: -32.84, -22.69]; for resmetirom 100 mg: MD -36.01% [95%CI: -41.54, -30.48]; P < .00001 for both) and FibroScan controlled attenuation parameter (for resmetirom 80 mg: MD -21.45 dBm [95%CI: -29.37, -13.52]; for resmetirom 100 mg: MD -25.51 dBm [95%CI: -33.53, -17.49]; P < .00001 for both). Resmetirom 80 mg outperformed placebo in NASH resolution and ≥2-point nonalcoholic fatty liver disease activity score reduction. Moreover, resmetirom 80 mg and 100 mg were superior to placebo in cytokeratin-18 (M30) reduction. Greater reductions in liver enzymes, lipids, and reverse triiodothyronine were observed in the resmetirom arms with no impact on triiodothyronine. Nausea and diarrhea were more common with resmetirom than with placebo; other adverse events were comparable.
CONCLUSION
Resmetirom improves hepatic fat content, liver enzymes, and fibrosis biomarkers in NASH patients. Resmetirom generally does not affect thyroid function and is well-tolerated.
PubMed: 38697306
DOI: 10.1016/j.eprac.2024.04.016 -
Cancer Treatment Reviews Jun 2024Head and neck squamous cell carcinoma (HNSCC) presents an ideal scenario for intratumoral therapies (IT), due to its local recurrence pattern and frequent superficial... (Review)
Review
BACKGROUND
Head and neck squamous cell carcinoma (HNSCC) presents an ideal scenario for intratumoral therapies (IT), due to its local recurrence pattern and frequent superficial extension. IT therapies aim to effect tumor regression by directly injecting antineoplastic agents into lesions. However, there is a lack of updated evidence regarding IT therapies in HNSCC.
PATIENTS AND METHODS
A systematic literature search (CRD42023462291) was conducted using WebOfScience, ClinicalTrials.gov, and conference abstracts from ESMO and ASCO, identifying for IT clinical trials in patients with HNSCC, from database creation to September 12th, 2023. Efficacy as well as safety (grade ≥ 3 treatment-related adverse events[trAEs]) were reported.
RESULTS
After evaluation of 1180 articles identified by the systematic search, 31 studies treating 948 patients were included. IT injectables were categorized as chemotherapies with or without electroporation (k = 4, N = 268), oncolytic viruses, plasmids, and bacteria-based (k = 16, N = 446), immunotherapies and EGFR-based therapies (k = 5, N = 160), radioenhancer particles (k = 2, N = 68), and calcium electroporation (k = 1, n = 6). EGFR-antisense plasmids, NBTXR3 radioenhancer and immune innate agonists show best overall response rates, at 83 %, 81 % and 44 % respectively. Eleven (35 %) studies added systemic therapy or radiotherapy to the IT injections. No study used predictive biomarkers to guide patient selection. 97 % studies were phase I-II. Safety-wise, electroporation and epinephrine-based injectable trials had significant local symptoms such as necrosis, fistula formation and post-injection dysphagia. Treatment-related tumor haemorrhages of various grades were described in several trials. Grade ≥ 3 trAEs attributable to the other therapies mainly comprised general symptoms such as fatigue. There were 3 injectable-related deaths across the systematic review.
CONCLUSION
This is the first review to summarize all available evidence of IT in HNSCC. As of today, IT therapies lack sufficient evidence to recommend their use in clinical practice. Continuing research on potential molecules, patient selection, safe administration of injections and controlled randomized trials are needed to assess their added benefit.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Antineoplastic Agents; Injections, Intralesional; Immunotherapy
PubMed: 38696902
DOI: 10.1016/j.ctrv.2024.102746 -
The Cochrane Database of Systematic... May 2024Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are drugs currently used for analgesia and sedation in newborn infants. Dexmedetomidine is increasingly being used in children and infants despite not being licenced for analgesia in this group.
OBJECTIVES
To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023.
SELECTION CRITERIA
We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety.
AUTHORS' CONCLUSIONS
Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.
Topics: Humans; Dexmedetomidine; Infant, Newborn; Respiration, Artificial; Hypnotics and Sedatives; Randomized Controlled Trials as Topic; Analgesics, Opioid; Morphine; Analgesia; Analgesics, Non-Narcotic
PubMed: 38695625
DOI: 10.1002/14651858.CD012361.pub2 -
Journal of Diabetes and Its... Jun 2024This systematic review and meta-analysis aimed to comprehensively evaluate the impact of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on visceral adipose tissue... (Meta-Analysis)
Meta-Analysis
Influence of glucagon-like peptide-1 receptor agonists on fat accumulation in patients with diabetes mellitus and non-alcoholic fatty liver disease or obesity: A systematic review and meta-analysis of randomized control trials.
AIM
This systematic review and meta-analysis aimed to comprehensively evaluate the impact of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in individuals with diabetes mellitus and non-alcoholic fatty liver disease (NAFLD) or obesity.
METHODS
A search of PubMed, Embase, and Web of Science until October 2023 identified 13 Randomized Controlled Trials (RCTs) meeting the inclusion criteria. Bias risk was assessed using the Cochrane risk-of-bias instrument. Statistical analysis utilized standard mean differences (SMD) in Review Manager 5.4. Heterogeneity and publication bias were assessed. This study used the protocol registered with the Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY2023110020).
RESULTS
GLP-1RA treatment significantly reduced VAT (SMD -0.55, 95 % CI [-0.90, -0.19]), SAT (SMD -0.59, 95 % CI [-0.99, -0.19]), body weight (SMD -1.07, 95 % CI [-1.67, -0.47]), and body mass index (BMI) (SMD -1.10, 95 % CI [-1.74, -0.47]) compared to controls. Heterogeneity was observed for VAT (I = 79 %, P < 0.01), SAT (I = 73 %, P < 0.01), body weight (I = 82 %, P < 0.01), and BMI (I = 82 %, P < 0.01). No publication bias was detected for VAT (P = 0.57) and SAT (P = 0.18). GLP-1RA treatment improved fasting blood glucose (FBG), postprandial glucose (PPG), hemoglobin A1c (HbA1c), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and fibrosis-4 (FIB-4).
CONCLUSIONS
This meta-analysis highlights GLP-1RAs' potential to reduce fat accumulation, body weight, and BMI and improve glycemic control in individuals with diabetes mellitus and NAFLD or obesity. These findings supported using GLP-1RAs as promising therapeutic agents to address abnormal adipose tissue distribution and metabolic dysfunction.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Glucagon-Like Peptide-1 Receptor; Obesity; Randomized Controlled Trials as Topic; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Intra-Abdominal Fat; Adiposity; Glucagon-Like Peptide-1 Receptor Agonists
PubMed: 38688179
DOI: 10.1016/j.jdiacomp.2024.108743 -
Therapeutic Innovation & Regulatory... Jul 2024Diabetes, a chronic disease worldwide, may be associated with a poorer prognosis in patients with coronavirus disease 2019 (COVID-19). While some antihyperglycemic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetes, a chronic disease worldwide, may be associated with a poorer prognosis in patients with coronavirus disease 2019 (COVID-19). While some antihyperglycemic medications may be beneficial, others may increase the risk of adverse clinical outcomes of COVID-19. We aimed to analyze the effect of antihyperglycemic medications on COVID-19.
METHODS
We searched the Web of Science, Cochrane Library, EMBASE, PubMed, and Scopus databases from December 2019 to June 2022 to identify literature related to patients with COVID-19 and type 2 diabetes mellitus (T2DM) treated with antihyperglycemic medications.
RESULTS
56 studies were included in the analysis. Metformin (OR 0.66; 95% CI 0.58-0.74; p < 0.05), Glucagon-like peptide-1 receptor agonist (GLP-1ra) (OR 0.73; 95% CI 0.59-0.91; p < 0.05), and sodium-dependent glucose transporters 2 inhibitor (SGLT 2i) (OR 0.77; 95% CI 0.69-0.87; p < 0.05) were associated with lower mortality risk, while insulin was associated with increased mortality risk (OR 1.40; 95% CI 1.26-1.55; p < 0.05). Meanwhile, metformin (OR 0.65; 95% CI 0.50-0.85; p < 0.05) and GLP-1ra (OR 0.84; 95% CI 0.76-0.94; p < 0.05) were significantly associated with decreased severe manifestation risk. What's more, metformin (OR 0.77; 95% CI 0.62-0.96; p < 0.05), GLP-1ra (OR 0.86; 95% CI 0.81-0.92; p < 0.05), and SGLT 2i (OR 0.87; 95% CI 0.79-0.97; p < 0.05) were also associated with a decreased risk of hospitalization, but insulin were associated with an increased risk of hospitalization (OR 1.31; 95% CI 1.12-1.52; p < 0.05). Nevertheless, the results of the subgroup analyses showed that the effects of different glucose-lowering agents on COVID-19 may be related to in-hospital use or out-hospital use, elderly or non-elderly patients use, and different geography.
CONCLUSION
Metformin, GLP-1ra, and SGLT 2i have shown a positive effect on clinical outcomes in COVID-19, particularly in non-elderly individuals. However, insulin use may pose a higher risk, especially in elderly patients, so need with caution. Meanwhile, DPP-4i, TZD, α-GLUi, and sulfonylureas appeared to have a neutral effect. These results need to be validated in future clinical studies.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; COVID-19; COVID-19 Drug Treatment; Observational Studies as Topic; Metformin; Glucagon-Like Peptide-1 Receptor; SARS-CoV-2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38683419
DOI: 10.1007/s43441-024-00633-6 -
The American Journal of Cardiology Jul 2024Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated clinically important weight loss effects in patients with type 2 diabetes. However, its effects... (Meta-Analysis)
Meta-Analysis Review
Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated clinically important weight loss effects in patients with type 2 diabetes. However, its effects on sustained weight loss in patients without diabetes remains unclear. Our objective was to examine the long-term efficacy and safety of semaglutide use for weight loss in patients with overweight/obesity and without diabetes. MEDLINE, EMBASE, and the Cochrane Libraries were systematically searched to identify randomized controlled trials that randomized participants with overweight/obesity and without diabetes to once-weekly 2.4 mg subcutaneous semaglutide versus placebo, with a follow-up of at least 68 weeks. The primary outcome was a change in relative body weight from baseline to the longest follow-up. Random-effects models with inverse variance weighting were used to estimate the weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs). A total of 4 randomized controlled trials (n = 3,087) were included. Of the 3 trials that provided body mass index by category (n = 2,783), 94.0% of the participants had a baseline body mass index ≥30 kg/m. Compared with placebo, the use of semaglutide was associated with substantial decreases in long-term relative (WMD -12.1%, 95% CI -13.5 to -10.7) and absolute body weight (WMD -12.3 kg, 95% CI -13.6 to -11.0). At the longest follow-up, 33.4% of participants randomized to semaglutide achieved ≥20% weight loss compared with 2.2% with placebo (RR 15.08, 95% CI 9.31 to 24.43). The risk of gastrointestinal adverse events was higher in participants who took semaglutide than placebo (RR 1:47, 95% CI 1.28 to 1.68); however, the majority of these events were transient and mild-to-moderate in severity and did not require treatment discontinuation. In conclusion, semaglutide is efficacious for sustained weight loss in patients with overweight/obesity and without diabetes.
Topics: Glucagon-Like Peptides; Humans; Weight Loss; Randomized Controlled Trials as Topic; Obesity; Treatment Outcome; Drug Administration Schedule; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Injections, Subcutaneous
PubMed: 38679221
DOI: 10.1016/j.amjcard.2024.04.041 -
International Journal of Stroke :... May 2024In patients surviving stroke, approximately 15% and 60% exhibit concurrent diabetes mellitus and overweight/obesity, respectively, necessitating heightened secondary... (Review)
Review
BACKGROUND
In patients surviving stroke, approximately 15% and 60% exhibit concurrent diabetes mellitus and overweight/obesity, respectively, necessitating heightened secondary prevention efforts. Despite glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrating improved outcomes for those with diabetes mellitus or obesity, their underutilization persists among eligible individuals. This systematic review and meta-analysis investigated the impact of GLP-1 RAs on stroke risk. The findings aim to optimize the implementation of this therapeutic strategy in patients surviving stroke with diabetes mellitus or obesity.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we systematically reviewed MEDLINE and Scopus until 15 November 2023. Eligible studies included randomized cardiovascular outcome trials (CVOTs) with individuals, with or without type 2 diabetes, randomized to either GLP-1 RA or placebo. The outcomes were total strokes, non-fatal strokes, and fatal strokes. Analyses were conducted using RevMan 5.4.1.
RESULTS
Among 1369 screened studies, 11 were eligible, encompassing 82,140 participants (34.6% women) with a cumulative follow-up of 247,596 person-years. In the GLP-1 RAs group, the stroke rate was significantly lower compared to placebo (RR: 0.85, 95% CI: 0.77-0.93; NNT: 200), showing no heterogeneity or interaction with administration frequency (daily vs weekly). In addition, the GLP-1 RAs group exhibited a significantly lower rate of non-fatal strokes compared to placebo (RR: 0.87, 95% CI: 0.79-0.95; NNT: 250), with no heterogeneity or interaction based on administration frequency, route (oral vs subcutaneous), or diabetes presence.
CONCLUSION
In this meta-analysis of 11 CVOTs with 82,140 participants, GLP-1 RAs demonstrated a 16% relative reduction in stroke risk compared to placebo. This finding may increase implementation of GLP-1 RAs by stroke specialists in individuals with stroke and comorbid diabetes mellitus or obesity.
DATA ACCESS STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
PubMed: 38676552
DOI: 10.1177/17474930241253988 -
International Journal of Molecular... Apr 2024The broadening application of glucagon-like peptide (GLP)-1 receptor agonists, specifically semaglutide (Ozempic) for the management of diabetes and obesity brings a... (Review)
Review
The broadening application of glucagon-like peptide (GLP)-1 receptor agonists, specifically semaglutide (Ozempic) for the management of diabetes and obesity brings a critical need to evaluate its safety profile, considering estimates of up to 20 million prescriptions per year in the US until 2035. This systematic review aims to assess the incidence of thyroid cancer and detail the spectrum of adverse events associated with semaglutide, focusing on its implications for patient care. Through a systematic search of PubMed, Scopus, and Embase databases up to December 2023, ten randomized controlled trials (RCTs) involving 14,550 participants, with 7830 receiving semaglutide, were analyzed, with an additional number of 18 studies that were separately discussed because they reported data from the same RCTs. The review focused on thyroid cancer incidence, gastrointestinal symptoms, and other significant adverse events attributed to semaglutide. The incidence of thyroid cancer in semaglutide-treated patients was less than 1%, suggesting no significant risk. Adverse events were predominantly gastrointestinal, including nausea (2.05% to 19.95%) and diarrhea (1.4% to 13%). Nasopharyngitis and vomiting were also notable, with mean prevalences of 8.23% and 5.97%, respectively. Other adverse events included increased lipase levels (mean of 6.5%), headaches (mean prevalence of 7.92%), decreased appetite (reported consistently at 7%), influenza symptoms (mean prevalence of 5.23%), dyspepsia (mean prevalence of 5.18%), and constipation (mean prevalence of 6.91%). Serious adverse events varied from 7% to 25.2%, highlighting the need for vigilant patient monitoring. These findings underscore the gastrointestinal nature of semaglutide's adverse events, which, while prevalent, did not significantly deter from its clinical benefits in the treatment landscape. This systematic review provides a comprehensive assessment of semaglutide's safety profile, with a focus on gastrointestinal adverse events and a low incidence of thyroid cancer. Despite the prevalence of gastrointestinal symptoms, semaglutide remains an efficacious option for managing diabetes and obesity. The detailed characterization of adverse events underscores the importance of monitoring and managing these effects in clinical practice, excluding the hypothesis of carcinogenesis.
Topics: Humans; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Hypoglycemic Agents; Incidence; Obesity; Thyroid Neoplasms
PubMed: 38673931
DOI: 10.3390/ijms25084346