Dissociable hindbrain GLP1R circuits for satiety and aversion

Nature, Journal Year: 2024, Volume and Issue: 632(8025), P. 585 - 593

Published: July 10, 2024

Language: Английский

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Glucagon-like Peptide-1 Receptor Agonists Associated Gastrointestinal Adverse Events: A Cross-Sectional Analysis of the National Institutes of Health All of Us Cohort

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 199 - 199

Published: Feb. 2, 2024

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used diabetes and obesity medications but have been associated with gastrointestinal (GI) adverse events. However, real-world evidence on comparative GI reaction profiles is limited. Objectives: This study aimed to evaluate events among GLP-1 RA users compare semaglutide, dulaglutide, liraglutide, exenatide safety regarding the profile. Methods: retrospective cross-sectional analysis utilized data 10,328 adults diabetes/obesity in National Institutes of Health All Us cohort. New were identified, examined. Logistic regression determined factors Results: The mean age population was 61.4 ± 12.6 years, 65.7% female, 51.3% White, they had a high comorbidity burden. Abdominal pain (57.6%) most common event, followed by constipation (30.4%), diarrhea (32.7%), nausea vomiting (23.4%), bleeding (15.9%), gastroparesis (5.1%), pancreatitis (3.4%). Dulaglutide liraglutide higher rates abdominal pain, constipation, diarrhea, than semaglutide exenatide. Liraglutide highest (4.0% 3.8%, respectively). Compared dulaglutide odds vomiting. They also semaglutide. No significant differences existed or risks between RAs. Conclusions: In this cohort, Differences agents, appearing safer other RAs, except for gastroparesis. These findings can inform selection considering risk factors. Further studies needed causal relationship concomitant medication use.

Language: Английский

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Obesity management: sex-specific considerations

Archives of Gynecology and Obstetrics, Journal Year: 2024, Volume and Issue: 309(5), P. 1745 - 1752

Published: Feb. 8, 2024

Obesity is a global health issue that has grown to epidemic proportions. According World Health Organisation (WHO), overweight and obesity are responsible for more than 1.2 million deaths in Europe each year, representing > 13% of the region's total mortality. Highly processed, calorie-dense foods reduced physical activity considered as primary drivers obesity, but genetic predisposition also plays significant role. Notably, prevalent women men most countries, several obesity-related comorbidities exhibit sex-specific pathways. Treatment indication depends on BMI (body mass index), well existing risk factors. To reduce obesity-associated comorbidities, permanent reduction body weight (at least) 5-10% recommended. guidelines suggest an escalating stepwise approach including lifestyle intervention, pharmacotherapy, bariatric-metabolic surgery. As cumulative evidence suggests differences loss outcomes, there growing interest considerations management. However, trials do not report or changes composition separately men. Here, we discuss state-of-the-art management focus current data about impact sex outcomes.

Language: Английский

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evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer’s disease

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 8, 2025

Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer's disease (AD), including neuroinflammation, represent potentially important and novel approaches. The glucagon-like peptide-1 receptor agonist semaglutide is approved for treatment type 2 diabetes obesity has an established safety profile. Semaglutide may have a disease-modifying, neuroprotective effect in AD through multimodal mechanisms neuroinflammatory, vascular, other AD-related processes. Large randomized controlled trials are needed to assess efficacy early-stage symptomatic AD. evoke evoke+ randomized, double-blind, placebo-controlled phase 3 investigating efficacy, safety, tolerability once-daily oral versus placebo Eligible participants were men or women aged 55–85 years with mild cognitive impairment dementia due confirmed amyloid abnormalities (assessed by positron emission tomography cerebrospinal fluid [CSF] analysis). After maximum 12-week screening phase, anticipated 1840 patients each trial (1:1) 156 weeks (104-week main 52-week extension). Randomized follow 8-week dose escalation regimen (3 mg [weeks 0–4], 7 4–8], 14 8–156]). primary endpoint semaglutide–placebo difference on change from baseline week 104 Clinical Dementia Rating – Sum Boxes score. Analyses plasma biomarkers, collected all participants, CSF sub-study (planned n = 210) will explore effects biomarkers neuroinflammation. Enrollment was undertaken between May 18, 2021, September 8, 2023. Completion trials' expected 2025, extension (in which investigators remain blinded assignment) continue October 2026. first large-scale investigate disease-modifying potential AD, exploration provide data be evaluating its utility Clinicaltrials.gov, NCT04777396 NCT04777409. Date: 02/03/2021

Language: Английский

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Semaglutide and cancer: A systematic review and meta-analysis

Diabetes & Metabolic Syndrome Clinical Research & Reviews, Journal Year: 2023, Volume and Issue: 17(9), P. 102834 - 102834

Published: July 27, 2023

Language: Английский

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Adverse events with risankizumab in the real world: postmarketing pharmacovigilance assessment of the FDA adverse event reporting system

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 15, 2023

Background Risankizumab, a humanized IgG1 monoclonal antibody that selectively inhibits IL-23, is currently approved for the treatment of moderate-to-severe plaque psoriasis and Crohn’s disease. The real-world safety study risankizumab in large- sample population lacking. aim this was to evaluate risankizumab-associated adverse events (AEs) characterize clinical priority through data mining Food Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods Disproportionality analyses were performed by calculating reporting odds ratios (RORs), deemed significant when lower limit 95% confidence interval greater than 1, quantify signals risankizumab-related AEs from second quarter (Q2) 2019 2022 Q3. Serious non-serious cases compared, prioritized using rating scale. Results Risankizumab recorded 10,235 reports, with 161 associated disproportionality. Of note, 37 PTs at least 30 classified as unexpected AEs, which uncovered drug label, such myocardial infarction, cataract, pancreatitis, diabetes mellitus, stress, nephrolithiasis. 74.68%, 25.32%, 0% graded weak, moderate, strong priorities, respectively. A total 48 pneumonia, cerebrovascular accident, loss consciousness, cardiac disorder, hepatic cirrhosis, thrombosis, more likely be reported serious AEs. median TTO moderate weak related 115 (IQR 16.75–305) 124 29–301) days, All disproportionality had early failure type features, indicating gradually decreased over time. Conclusion Our found potential new AE provided valuable evidence clinicians mitigate risk based on an extensive analysis large-scale postmarketing international database.

Language: Английский

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Case Report: Semaglutide-associated depression: a report of two cases

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 29, 2023

Semaglutide, as a glucagon-like peptide-1 receptor agonist (GLP-1 RA), was approved for glucose control in type 2 diabetes mellitus 2017 and weight loss 2021 by the U.S. Food Drug Administration (FDA). No psychiatric adverse effect associated with semaglutide has been reported so far. Here we report two cases of semaglutide-associated depression. One is middle-aged man no previous history depression who developed depressive symptoms about 1 month after taking semaglutide. The other one woman recurrent disorder whose also recurred treatment. Depression improved or relieved discontinuation both cases. Possible effects should be taken into consideration when administered to patients.

Language: Английский

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Assessment of Thyroid Carcinogenic Risk and Safety Profile of GLP1-RA Semaglutide (Ozempic) Therapy for Diabetes Mellitus and Obesity: A Systematic Literature Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4346 - 4346

Published: April 15, 2024

The broadening application of glucagon-like peptide (GLP)-1 receptor agonists, specifically semaglutide (Ozempic) for the management diabetes and obesity brings a critical need to evaluate its safety profile, considering estimates up 20 million prescriptions per year in US until 2035. This systematic review aims assess incidence thyroid cancer detail spectrum adverse events associated with semaglutide, focusing on implications patient care. Through search PubMed, Scopus, Embase databases December 2023, ten randomized controlled trials (RCTs) involving 14,550 participants, 7830 receiving were analyzed, an additional number 18 studies that separately discussed because they reported data from same RCTs. focused incidence, gastrointestinal symptoms, other significant attributed semaglutide. semaglutide-treated patients was less than 1%, suggesting no risk. Adverse predominantly gastrointestinal, including nausea (2.05% 19.95%) diarrhea (1.4% 13%). Nasopharyngitis vomiting also notable, mean prevalences 8.23% 5.97%, respectively. Other included increased lipase levels (mean 6.5%), headaches prevalence 7.92%), decreased appetite (reported consistently at 7%), influenza symptoms 5.23%), dyspepsia 5.18%), constipation 6.91%). Serious varied 7% 25.2%, highlighting vigilant monitoring. These findings underscore nature semaglutide’s events, which, while prevalent, did not significantly deter clinical benefits treatment landscape. provides comprehensive assessment focus low cancer. Despite remains efficacious option managing obesity. detailed characterization underscores importance monitoring these effects practice, excluding hypothesis carcinogenesis.

Language: Английский

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Anti-inflammatory benefits of semaglutide: State of the art

Journal of Clinical & Translational Endocrinology, Journal Year: 2024, Volume and Issue: 36, P. 100340 - 100340

Published: March 28, 2024

Individuals with diabetes often have chronic inflammation and high levels of inflammatory cytokines, leading to insulin resistance complications. Anti-inflammatory agents are proposed prevent these issues, including using antidiabetic medications anti-inflammatory properties like semaglutide, a GLP-1 analogue. Semaglutide not only lowers glucose but also shows potential effects. Studies suggest it can modulate responses benefit those diabetes. However, the exact mechanisms its effects fully understood. This review aims discuss latest findings on semaglutide's pathways involved.

Language: Английский

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Is pitolisant safe for clinical use? A retrospective pharmacovigilance study focus on the post‐marketing safety

Pharmacology Research & Perspectives, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 4, 2024

Pitolisant, a novel histamine H3-receptor antagonist, holds significant promise for treating narcolepsy. However, petition, which highlighted that pitolisant was associated with deaths during clinical trials, has propelled it into the spotlight of widespread societal attention on April 3, 2023. Till now, safety remains heatedly debated topic. This study aimed to offer comprehensive assessment profile in real-world settings. Adverse event reports where primary suspect drug were extracted from FDA Event Reporting System database. The characteristics and concomitant drugs pitolisant-associated adverse events analyzed. potential signals explored using four disproportionality analysis methods. Furthermore, difference investigated concerning sex, age, weight, dose. A total 526 1695 as suspected identified. most generally mild short duration. highly intricate, mainly included narcolepsy well antidepressants. Seven new emerged. exhibited no differences across age dose groups, although slight variations observed relation sex weight. findings death life-threatening outcomes underscore importance enhanced monitoring cardiac respiratory reactions when utilizing pitolisant. provided broader understanding

Language: Английский

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