Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: unknown, P. 159048 - 159048
Published: Dec. 1, 2024
Language: Английский
Diabetes Care, Journal Year: 2024, Volume and Issue: unknown
Published: June 6, 2024
The development of glucagon-like peptide 1 receptor agonists (GLP-1RA) for type 2 diabetes and obesity was followed by data establishing the cardiorenal benefits GLP-1RA in select patient populations. In ongoing trials investigators are interrogating efficacy these agents new indications, including metabolic liver disease, peripheral artery Parkinson Alzheimer disease. success GLP-1–based medicines has spurred molecular entities combinations with unique pharmacokinetic pharmacodynamic profiles, exemplified tirzepatide, a GIP-GLP-1 coagonist. Simultaneously, investigational molecules such as maritide block GIP activate GLP-1 receptor, whereas retatrutide survodutide enable simultaneous activation glucagon receptors. Here I highlight evidence medicines, while discussing that inform safety, focusing on muscle strength, bone density fractures, exercise capacity, gastrointestinal motility, retained gastric contents anesthesia, pancreatic biliary tract disorders, risk cancer. Rapid progress highly efficacious anticipated differentiation newer subsets will provide greater opportunities use personalized medicine approaches to improve health people living cardiometabolic disorders.
Language: Английский
Citations
77
Cardiovascular Diabetology, Journal Year: 2025, Volume and Issue: 24(1)
Published: Jan. 29, 2025
Language: Английский
Citations
2
Molecular Metabolism, Journal Year: 2024, Volume and Issue: 83, P. 101924 - 101924
Published: March 22, 2024
Theut microbiota increases energy availability through fermentation of dietary fibers to short-chain fatty acids in conventionally raised mice. Energy deficiency germ-free (GF) mice glucagon-like peptide-1 (GLP-1) levels, which slows intestinal transit. To further analyze the role GLP-1-mediated signaling this model deficiency, we re-derived lacking GLP-1 receptor (GLP-1R KO) as GF. GLP-1R KO were rederived GF hysterectomy and monitored for 30 weeks. Mice subjected rescue experiments either feeding an energy-rich diet or colonization with a normal cecal microbiota. Histology function assessed at different ages. Intestinal organoids investigate stemness. Unexpectedly, 25% died before 20 weeks age, associated enlarged ceca, increased water content, colonic expression apical ion transporters, reduced number goblet cells loss epithelial integrity. Colonocytes from energy-deprived exhibited ER-stress; mitochondrial fragmentation, oxygen levels Restoring by Western-style gut normalized phenotypes prevented lethality. Our findings reveal heretofore unrecognized maintenance physiology survival during deprivation.
Language: Английский
Citations
6
Molecular Metabolism, Journal Year: 2024, Volume and Issue: 89, P. 102019 - 102019
Published: Aug. 30, 2024
The development of glucagon-like peptide-1 receptor (GLP-1R) agonists for the treatment type 2 diabetes and obesity has been accompanied by evidence anti-inflammatory cytoprotective actions in heart, blood vessels, kidney, brain. Whether GLP-1R might be useful clinically attenuating deterioration cognitive dysfunction reducing progression Alzheimer's disease remains uncertain. Here we evaluated semaglutide tirzepatide, distinct GLP-1 medicines, two mouse models neurodegeneration. Semaglutide reduced body weight improved glucose tolerance 12-month-old male female 5XFAD APP/PS1 mice, consistent with pharmacological engagement GLP-1R. Nevertheless, amyloid plaque density was not different cerebral cortex, hippocampus, or subiculum semaglutide-treated mice. IBA1 GFAP expression were increased hippocampus mice but semaglutide. Moreover, parameters neurobehavioral function using Open Field testing Morris water maze following To explore whether incretin therapies more effective younger studied tirzepatide action 6-month-old Neither nor modified extent accumulation, hippocampal IBA1+ GFAP+ cells, testing, despite improving weight. mRNA biomarkers inflammation neurodegeneration after tirzepatide. Collectively, these findings reveal preservation metabolic yet inability to detect improvement structural functional disease.
Language: Английский
Citations
6
Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15
Published: June 7, 2024
Background Tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) agonist, is indicated for chronic weight management in adults with obesity or overweight as an adjunct to reduced-calorie diet increased physical activity. However, the safety profile of Tirzepatide-associated adverse events requires comprehensive evaluation. Methods The AE reports from first quarter 2022 third 2023 were selected by exploring FDA Adverse Event Reporting System (FAERS) database. new unexpected potenial signals detected using disproportionality analysis, including reporting odds ratio(ROR), proportional ratio (PRR) Bayesian confidence propagation neural network (BCPNN) empirical Bayes geometric mean(EBGM). Then MedDRA was used systematically classify results. Results A total 1,904,481 case obtained 2022Q2 2023Q3. Forty-sixth tirzepatide-induced ADRs at preferred terms (PTs) level are associated 8 system organ class In addition, this study uncovered multiple anticipated ADRs, such gastrooesophageal reflux disease, dyspepsia, vomiting, line drug labels. Moreover, significant PTs level, incorrect dose administered, injection site haemorrhage, appetite, discovered linked Injury, poisoning, procedural complications, General disorders administration conditions, Metabolism nutrition Organ Class level. Conclusion This offered perspectives on monitoring, surveillance, reactions related tirzepatide. outcomes severe their respective detection signals, along event important consider efforts enhance clinical medication when
Language: Английский
Citations
5
Life Metabolism, Journal Year: 2024, Volume and Issue: 3(6)
Published: Aug. 7, 2024
Abstract Type 2 diabetes mellitus (T2DM) is closely associated with obesity, while interactions between the two diseases remain to be fully elucidated. To this point, we offer perspective introduce a set of new insights into interpretation T2DM spanning etiology, pathogenesis, and treatment approaches. These include definition as an energy surplus-induced characterized by gradual decline β cell insulin secretion function, which ultimately aims prevent onset severe obesity through mechanisms weight loss. The body employs three adaptive strategies in response surplus: first one adipose tissue expansion store for gain under normal conditions; second resistance slow down overweight third following failure reverse obese conditions. primary signaling molecules driving compensatory responses are adenosine derivatives, such triphosphate (ATP), acetyl coenzyme A (acetyl-CoA), reduced nicotinamide adenine dinucleotide (NADH). exert their effects allosteric, post-translational, transcriptional regulation metabolic pathways. suggest that protective defense against excessive adiposity avert obesity. provides unified framework explaining opens avenues study T2DM.
Language: Английский
Citations
5
Nature Medicine, Journal Year: 2024, Volume and Issue: 30(8), P. 2337 - 2342
Published: May 15, 2024
Language: Английский
Citations
4
Gut, Journal Year: 2024, Volume and Issue: unknown, P. gutjnl - 334023
Published: Nov. 26, 2024
Clinically effective pharmacological treatment(s) for metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form steatohepatitis (MASH) represent a largely unmet need in medicine. Since glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been licensed the treatment of type 2 diabetes mellitus obesity, they were one first drug classes to be examined individuals with MASLD/MASH. Successful phase randomised clinical trials these agents resulted progression 3 (principally testing long-term efficacy subcutaneous semaglutide). Over last few years, addition GLP-1RAs, newer glucose-dependent insulinotropic peptide and/or glucagon agonist functions tested, increasing evidence from histological improvements MASLD/MASH, as well benefits on MASLD-related extrahepatic complications. Based this background evidence, single, dual or triple incretin are becoming an attractive promising option MASLD MASH, particularly coexisting obesity mellitus. In narrative review, we examine rapidly expanding body supporting role incretin-based pharmacotherapies delaying reversing MASH progression. We also discuss biology incretins putative hepatoprotective mechanisms managing MASH.
Language: Английский
Citations
4
Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16
Published: March 25, 2025
Introduction Obesity is a worldwide health concern frequently addressed by weight reduction strategies, including bariatric surgery and restricted diets. While effective, these approaches can result in complications, Guillain-Barré Syndrome (GBS), rare but serious autoimmune disorder. This study aims to analyze clinical neurophysiological features of diet-induced GBS compare them cases linked with surgery. Methods We retrospectively reviewed medical records five patients admitted our institution between August 2012 2022, who developed during active dieting resulting significant loss. Clinical presentations, laboratory results, findings, nutritional status treatment were analyzed. Additionally, we performed literature review comparing nineteen previously reported instances surgery-associated GBS. Results All exhibited acute, symmetrical limb weakness primarily affecting the lower extremities, accompanied diminished tendon reflexes. Neurophysiological assessments revealed axonal damage all cases, albuminocytologic dissociation was present two patients. Three received intravenous immunoglobulin (IVIG) therapy, while remaining underwent therapy alone. achieved full recovery within 6 months. Notably, rate loss observed significantly exceeded recommended safe guidelines. Discussion Rapid substantial may play role triggering GBS, possibly due deficiencies or immune dysregulation. Clinicians should recognize potential neurological risks associated aggressive weight-loss strategies. Early diagnosis appropriate intervention are crucial for favorable outcomes preventing complications.
Language: Английский
Citations
0
Medicina, Journal Year: 2025, Volume and Issue: 61(4), P. 678 - 678
Published: April 7, 2025
Growing interest in incretin-based therapies for diabetes mellitus has led to an increased evaluation of their potential effects on cancer development. This review aims synthesize recent evidence regarding the relationship between and risk. We conducted a comprehensive literature focusing studies investigating dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists relation various malignancies. Current findings suggest that while these demonstrate benefits, including weight reduction metabolic regulation, concerns remain long-term safety profile. Notably, some indicate risk thyroid pancreatic cancers, others report protective against prostate, colorectal, breast cancers. Given complexity effects, further post-marketing surveillance are warranted. highlights need careful clinical assessment when prescribing patients who may be at cancer.
Language: Английский
Citations
0