UNASSIGNED: The aim of this review was to provide all the pharmacokinetic data for semaglutide in humans concerning its pharmacokinetics after subcutaneously and oral applications in healthy and diseased populations, to provide recommendations for clinical use.
UNASSIGNED: The PubMed and Embase databases were searched to screen studies associated with the pharmacokinetics of semaglutide. The pharmacokinetic parameters included area under the curve plasma concentrations (AUC), maximal plasma concentration (Cmax), time to Cmax, half-life (t1/2), and clearance. The systematic literature search retrieved 17 articles including data on pharmacokinetic profiles after subcutaneously and oral applications of semaglutide, and at least one of the above pharmacokinetic parameter was reported in all included studies.
UNASSIGNED: Semaglutide has a predictable pharmacokinetic profile with a long t1/2 that allows for once-weekly subcutaneous administration. The AUC and Cmax of both oral and subcutaneous semaglutide increased with dose. Food and various dosing conditions including water volume and dosing schedules can affect the oral semaglutide exposure. There are limited drug-drug interactions and no dosing adjustments in patients with upper gastrointestinal disease, renal impairment or hepatic impairment. Body weight may affect semaglutide exposure, but further studies are needed to confirm this.
UNASSIGNED: This review encompasses all the pharmacokinetic data for subcutaneous and oral semaglutide in both healthy and diseased participants. The existing pharmacokinetic data can assist in developing and evaluating pharmacokinetic models of semaglutide and will help clinicians predict semaglutide dosages. In addition, it can also help optimize future clinical trials.

暂无摘要。

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of semaglutide 2.4 mg, a glucagon-like peptide-1 receptor agonist, by race and ethnicity, across three phase 3 trials.
METHODS: The Semaglutide Treatment Effect in People with Obesity (STEP) clinical trials evaluated the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg. Here, STEP 1 and 3 data were pooled for analysis; STEP 2 data were examined separately. All analyses were conducted using data from racial and ethnic subgroups. The primary outcome was the estimated treatment difference in percent body weight change for semaglutide 2.4 mg versus placebo.
RESULTS: Participants reported race as White (STEP 1 and 3, 75.3%; STEP 2, 59.4%), Black (8.8%; 8.9%), Asian (10.6%; 27.3%), or other racial group (5.3%; 4.4%); and ethnicity as Hispanic or Latino (13.9%; 11.9%) or not Hispanic or Latino (83.9%; 88.1%). There were no significant interactions between treatment effect and race (STEP 1 and 3: p ≥ 0.07; STEP 2: p ≥ 0.15) or ethnicity (p ≥ 0.40; p ≥ 0.85). The safety of semaglutide 2.4 mg was consistent across subgroups.
CONCLUSIONS: The treatment effect of semaglutide was statistically significant versus placebo and clinically relevant across all racial and ethnic subgroups in STEP 1 and 3 and STEP 2. All subgroups across both samples demonstrated good tolerability.

Background and Objectives: The rise in global diabetes cases, reaching a staggering 529 million in 2021 from 108 million in 1980, underscores the urgency of addressing its complications, notably macrovascular ones like coronary artery, cerebrovascular, and peripheral artery diseases, which contribute to over 50% of diabetes mortality. Atherosclerosis, linked to hyperglycemia-induced endothelial dysfunction, is pivotal in cardiovascular disease development. Cytokines, including pentraxin 3 (PTX3), copeptin, lipoprotein(a) [Lp(a)], and matrix metalloproteinase-9 (MMP-9), influence atherosclerosis progression and plaque vulnerability. Inhibiting atherosclerosis progression is crucial, especially in diabetic individuals. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), increasingly used for type 2 diabetes, show promise in reducing the cardiovascular risk, sparking interest in their effects on atherogenesis. This study sought to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on biomarkers that indicate the instability of atherosclerotic plaques. These biomarkers include pentraxin 3 (PTX3), copeptin (CPC), matrix metalloproteinase-9 (MMP-9), and lipoprotein(a) [Lp(a)]. Materials and Methods: A total of 34 participants, ranging in age from 41 to 81 years (with an average age of 61), who had been diagnosed with type 2 diabetes mellitus (with a median HbA1c level of 8.8%), dyslipidemia, and verified atherosclerosis using B-mode ultrasonography, were included in the study. All subjects were eligible to initiate treatment with a GLP-1 RA-dulaglutide. Results: Significant reductions in anthropometric parameters, blood pressure, fasting glucose levels, and HbA1c levels were observed posttreatment. Moreover, a notable decrease in biochemical markers associated with atherosclerotic plaque instability, particularly PTX3 and MMP-9 (p < 0.001), as well as Lp(a) (p < 0.05), was evident following the GLP-1 RA intervention. Conclusions: These findings underscore the potential of GLP-1 RAs in mitigating atherosclerosis progression and plaque vulnerability, thus enhancing cardiovascular outcomes in individuals with type 2 diabetes mellitus.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), currently marketed for type 2 diabetes and obesity, may offer novel mechanisms to delay or prevent neurotoxicity associated with Alzheimer\'s disease (AD). The impact of semaglutide in amyloid positivity (ISAP) trial is investigating whether the GLP-1 RA semaglutide reduces accumulation in the brain of cortical tau protein and neuroinflammation in individuals with preclinical/prodromal AD.
METHODS: ISAP is an investigator-led, randomised, double-blind, superiority trial of oral semaglutide compared with placebo. Up to 88 individuals aged ≥55 years with brain amyloid positivity as assessed by positron emission tomography (PET) or cerebrospinal fluid, and no or mild cognitive impairment, will be randomised. People with the low-affinity binding variant of the rs6971 allele of the Translocator Protein 18 kDa (TSPO) gene, which can interfere with interpreting TSPO PET scans (a measure of neuroinflammation), will be excluded.At baseline, participants undergo tau, TSPO PET and MRI scanning, and provide data on physical activity and cognition. Eligible individuals are randomised in a 1:1 ratio to once-daily oral semaglutide or placebo, starting at 3 mg and up-titrating to 14 mg over 8 weeks. They will attend safety visits and provide blood samples to measure AD biomarkers at weeks 4, 8, 26 and 39. All cognitive assessments are repeated at week 26. The last study visit will be at week 52, when all baseline measurements will be repeated. The primary end point is the 1-year change in tau PET signal.
BACKGROUND: The study was approved by the West Midlands-Edgbaston Research Ethics Committee (22/WM/0013). The results of the study will be disseminated through scientific presentations and peer-reviewed publications.
BACKGROUND: ISRCTN71283871.

BACKGROUND: Semaglutide is increasingly used for the treatment of type 2 diabetes mellitus, overweight and other conditions. It is well known that semaglutide lowers blood glucose levels and leads to significant weight loss. Still, a systematic review has yet to investigate the adverse effects with semaglutide for all patient groups.
METHODS: We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medline, Embase, Latin American and Caribbean Health Sciences Literature, Science Citation Index Expanded, Conference Proceedings Citation Index-Science) and clinical trial registries from their inception and onwards to identify relevant randomised clinical trials. We expect to conduct the literature search in July 2024. Two review authors will independently extract data and perform risk-of-bias assessments. We will include randomised clinical trials comparing oral or subcutaneous semaglutide versus placebo. Primary outcomes will be all-cause mortality and serious adverse events. Secondary outcomes will be myocardial infarction, stroke, all-cause hospitalisation and non-serious adverse events. Data will be synthesised by meta-analyses and trial sequential analysis; risk of bias will be assessed with Cochrane Risk of Bias tool-version 2, an eight-step procedure will be used to assess if the thresholds for statistical and clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations.
BACKGROUND: This protocol does not present any results. Findings of this systematic review will be published in international peer-reviewed scientific journals.
UNASSIGNED: CRD42024499511.

暂无摘要。

UNASSIGNED: Glucagon-like peptide-1 receptor-agonists (GLP-1ra), such as semaglutide, have emerged as promising treatments, demonstrating sustained weight reduction and metabolic benefits. This study aims to assess the impact of oral and subcutaneous semaglutide on body composition and metabolic parameters in patients with T2DM and obesity.
UNASSIGNED: A 24-week quasi-experimental retrospective study including adults with T2DM and obesity (BMI ≥ 30 kg/m²) who were treated with either daily-oral or weekly-subcutaneous semaglutide. Body composition was measured using bioelectrical impedance analysis, evaluating fat mass, fat-free mass, total body water, skeletal muscle mass, and whole-body phase angle. Analytical parameters included lipid profile and glycaemic control. Statistical analyses were performed using SPSS v.26.
UNASSIGNED: Participants (n=88) experienced significant weight loss after treatment with semaglutide (9.5% in subcutaneous, 9.4% in oral, P<0.001). Weight reduction primarily resulted from fat mass reduction without substantial lean mass compromise. Visceral fat area decreased, whiles phase-angle remained stable. Improvements in lipid profiles and glycaemic control were observed, with a decrease in both HbA1c and insulin requirements. Multivariate analysis demonstrated comparable impacts of oral and subcutaneous semaglutide on body composition.
UNASSIGNED: Semaglutide, administered orally or subcutaneously, demonstrated positive effects on body composition, metabolic and glycaemic control in patients with T2DM and obesity. This real-world study highlights the potential of bioelectrical impedance analysis in assessing antidiabetic drugs\' impact on body composition, providing valuable insights for future research and clinical applications.

The purpose of this study was to explore the effect of Semaglutide on intrauterine adhesions and discover new drugs for such adhesions. In this study, the cell model was simulated by TGF-β1-induced human endometrial epithelial cells, and the animal model was established through mechanical curettage and inflammatory stimulation. After co-culturing with TGF-β1 with or without different concentrations of Semaglutide for 48 h, cells were collected for RT-qPCR and Western blotting analyses. Three doses were subcutaneously injected into experimental mice once a day for two weeks, while the control group received sterile ddH2O. The serum and uterine tissues of the mice were collected. HE and Masson staining were used for the uterine histomorphological and pathological analyses. RT-qPCR and Western blotting were used for mRNA and protein expression analyses. Serum indicators were detected using ELISA kits. The results showed that Semaglutide significantly reduced the mRNA levels of fibrosis indicators ACTA2, COL1A1, and FN and inflammatory indicators TNF-α, IL-6, and NF-κB in the two models. Semaglutide improved endometrium morphology, increased the number of endometrial glands, and reduced collagen deposition in IUA mice. The results also showed that Semaglutide could inhibit vimentin, E-Cadherin, and N-Cadherin in the two models. In summary, Semaglutide can ameliorate fibrosis and inflammation of intrauterine adhesions as well as inhibit epithelial-mesenchymal transition in IUA models.

UNASSIGNED: Heart failure with preserved ejection fraction (HFpEF) is a highly heterogeneous syndrome, making it challenging to improve prognosis with pharmacotherapy. Obesity is one of the leading phenotypes of HFpEF, and its prevalence continues to grow worldwide. Consequently, obesity-targeted interventions have attracted attention as a novel treatment strategy for HFpEF.
UNASSIGNED: The authors review the association between the pathogenesis of obesity and HFpEF and the potential for obesity-targeted pharmacotherapeutic strategies in HFpEF, together with the latest evidence. The literature search was conducted in PubMed up to April 2024.
UNASSIGNED: The STEP HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF) and SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trials recently demonstrated that the glucagon-like peptide 1 analogue, semaglutide, improves various aspects of clinical outcomes in obese HFpEF patients and significantly reduces cardiovascular and heart failure events in non-diabetic obese patients, along with a substantial weight loss. Future clinical trials with other incretin mimetics with more potent weight loss and sub-analyses of the SELECT trial may further emphasize the importance of the obesity phenotype-based approach in the treatment of HFpEF.