This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use o...This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use of glucagon-like peptide 1 receptor agonists,especially when used in combination therapy.However,despite their notable efficacy,these drugs were not initially designed to target MASLD directly.In a groundbreaking development,the Food and Drug Administration has recently approved resmetirom,the first treatment specifically aimed at reducing liver fibrosis in metabolic-associated steatohepatitis.Resmetirom,an orally administered,liver-directed thyroid hormone beta-selective agonist,acts directly on intrahepatic pathways,enhancing its therapeutic potential and marking the beginning of a new era in the treatment of MASLD.Furthermore,the integration of lifestyle modifications into liver disease management is an essential component that should be considered and reinforced.By incorporating dietary changes and regular physical exercise into treatment,patients may achieve improved outcomes,reducing the need for pharmacological interventions and/or improving treatment efficacy.As a complement to medical therapies,lifestyle factors should not be overlooked in the broader strategy for managing MASLD.展开更多
Glucagon-like peptide-1 (GLP-1) and its receptor agonists (GLP-1RAs) are wellestablishedtherapies for metabolic conditions such as type 2 diabetes and obesitydue to their ability to enhance insulin secretion, promote ...Glucagon-like peptide-1 (GLP-1) and its receptor agonists (GLP-1RAs) are wellestablishedtherapies for metabolic conditions such as type 2 diabetes and obesitydue to their ability to enhance insulin secretion, promote weight loss, and regulateblood glucose levels. Emerging evidence, however, indicates that GLP-1RAs mayalso have therapeutic potential in inflammatory and autoimmune conditions. Thisreview explores the evolving role of GLP-1RAs in managing rheumatic diseases,including osteoarthritis, rheumatoid arthritis, psoriatic arthritis, and systemiclupus erythematosus. Studies suggest that GLP-1RAs reduce inflammation bymodulating immune cell activity, increasing anti-inflammatory cytokine production,shifting macrophage polarization toward an anti-inflammatory phenotype,and enhancing regulatory T-cell function to maintain immune homeostasis. Theseimmunomodulatory effects point toward a promising adjunctive strategy incurrent clinical practice for patients with rheumatic diseases, particularly thosewith metabolic comorbidities. Further clinical trials are warranted to validatethese findings, clarify underlying mechanisms, and assess long-term safety,ultimately paving the way for novel treatment approaches in rheumatology.展开更多
BACKGROUND Atrial fibrillation(AF)stands as the most prevalent type of arrhythmia,affecting approximately 60 million individuals world-wide.Although antiarrhythmic drugs(AADs)remain the gold standard for AF treatment,...BACKGROUND Atrial fibrillation(AF)stands as the most prevalent type of arrhythmia,affecting approximately 60 million individuals world-wide.Although antiarrhythmic drugs(AADs)remain the gold standard for AF treatment,glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are arising as potential therapeutic alternatives.AIM To evaluate the impact of GLP-1 RAs on the incidence of AF.METHODS Inclusion criteria included systematic reviews(SRs)that based their analyses on clinical trials,observational studies,controlled trials and network meta-analyses.A total of 8 SRs were selected for data extraction,focusing on semaglutide,liraglutide and dulaglutide.Additionally,the effects of GLP-1 RAs on AF incidence were compared with those of sodium-glucose co-transporter 2(SGLT2)inhibitors.RESULTS Findings indicate that semaglutide,evaluated in the largest patient cohort across the 8 SRs,consistently reduced AF incidence.However,dulaglutide and liraglutide exhibited inconsistent effects.Notably,as opposed to variable outcomes associated with GLP-1 RAs,SGLT2 inhibitors a class of antidiabetic agents with weight-reducing properties exhibit significant cardiovascular benefits,including reductions in both AF and atrial flutter.CONCLUSION GLP-1 RAs emerge as a promising and potential alternative for AADs in reduction of incidence of AF.However,further research is required to fully determine their therapeutic potential and long-term cardiovascular effects.展开更多
Obesity is a global pandemic that has been threatening the worldwide population.It has been reported to be associated with an increase in the risk of chronic diseases such as type 2 diabetes mellitus(T2DM),cardiovascu...Obesity is a global pandemic that has been threatening the worldwide population.It has been reported to be associated with an increase in the risk of chronic diseases such as type 2 diabetes mellitus(T2DM),cardiovascular disease,and other diseases,including some malignancies.Currently,the first line of management includes lifestyle modifications.However,recently,bariatric surgeries were introduced to combat obesity.The previous modalities of management are always challenging since lifestyle could have limited long-term effectiveness and difficulty to achieve,and surgeries are invasive and also require a lifestyle modification and commitment.Glucagon-like peptide-1 receptor agonists(GLP-1RAs)were initially introduced as a rising star for managing T2DM,with patients benefiting from the control of blood sugar and weight loss.These medications work by enhancing feelings of fullness,slowing down digestion,and ultimately reducing calorie intake.However,GLP-1RAs are not without side effects and have some costs.Common side effects include gastrointestinal(GI)adverse events such as nausea,vomiting,diarrhea,and a lack of GI motility,which is the main mechanism through which the drug induces a feeling of fullness and promotes weight loss,potentially resulting in treatment discontinuation.More serious,though less frequent,risks include pancreatitis,gallbladder diseases,and,rarely,thyroid Ccell cancers.This review aimed to discuss the globally emerging role of GLP-1RAs in obesity management and highlight some safety considerations for patients taking these drugs.展开更多
BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RAs)play a key role in managing type 2 diabetes mellitus(T2DM).Transitioning between different GLP-1RA has been proposed as a treatment strategy.AIM To investi...BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RAs)play a key role in managing type 2 diabetes mellitus(T2DM).Transitioning between different GLP-1RA has been proposed as a treatment strategy.AIM To investigate switching patterns between GLP-1RA and their impact on glycemic control.METHODS A retrospective study involving patients with T2DM who initiated GLP-1RA therapy between 2009 and 2021 and transitioned to another GLP-1RA.Baseline glycated hemoglobin(HbA1c)was defined as the most recent measurement within 1 year prior to switching,and follow-up HbA1c was the first measurement recorded 4-15 months post-switch.RESULTS Among 70654 patients initiating GLP-1RA therapy,18047(25.5%)switched regimens.In the 13970 patients with available HbA1c,levels decreased from 8.5%±1.6%to 7.6%±1.4%(P<0.001).HbA1c decreased in 78.3%(10943/13970)of these patients,with the most frequent improvement observed in those switching from daily to weekly GLP-1RA(81%,5582/6890).CONCLUSION Switching between GLP-1RAs can serve as a practical alternative to treatment intensification for effectively managing T2DM.展开更多
BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are increasingly being used to treat type 2 diabetes mellitus(T2DM)and obesity.Although GLP-1RAs delay gastric emptying,their impact on gastric mucosal vis...BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are increasingly being used to treat type 2 diabetes mellitus(T2DM)and obesity.Although GLP-1RAs delay gastric emptying,their impact on gastric mucosal visibility during upper endoscopy remains uncertain,especially in Asian patients.AIM To investigate the association between GLP-1RA treatment and gastric mucosal visibility during upper endoscopy in Asian patients with T2DM.METHODS The study population included Korean patients who underwent esophagogastroduodenoscopy(EGD)with concomitant GLP-1RA or dipeptidyl peptidase 4 inhibitor(DPP4i)for the treatment of T2DM.A 1:2 propensity score matching between GLP-1RA and DPP4i users resulted in 198 matched patients and 295 matched patients in each group,respectively.Gastric mucosal visibility was assessed by reviewing endoscopy images with a validated scale(POLPREP).In addition,the rates of aborted and repeat EGD and pulmonary aspiration were also assessed.RESULTS Of the 493 matched patients,mean body mass index was 26.0 kg/m^(2).The rate of inadequate gastric mucosal visibility(gastric POLPREP score 0 or 1)was significantly higher in GLP-1RA group than matched DPP4i group(8.6%vs 1.4%,P=0.0007).The rates of aborted EGD and repeat EGD were also significantly higher in GLP-1RA than DPP4i group(7.6%vs 0.7%in both aborted and repeat EGD,P=0.0011).Multivariable logistic regression revealed GLP-1RA use as an independent risk factor for both inadequate gastric mucosal visibility(odds ratio=6.143,95%confidence interval:2.289,20.318,P=0.0008)and aborted EGD(odds ratio=11.099,95%confidence interval:3.172,63.760,P=0.0010).Despite gastric residue,no pulmonary aspiration was reported in either group.CONCLUSION GLP-1RA use was associated with a higher risk of inadequate gastric mucosal visibility and aborted and repeat procedures during upper gastrointestinal endoscopy in Korean patients with T2DM while pulmonary aspiration was not observed.展开更多
The global prevalence of diabetes has surged in recent years,with diabetic kidney disease(DKD)emerging as a major complication.Traditional therapies have had limited success in slowing progression to end-stage kidney ...The global prevalence of diabetes has surged in recent years,with diabetic kidney disease(DKD)emerging as a major complication.Traditional therapies have had limited success in slowing progression to end-stage kidney disease.However,novel therapies,particularly sodium-glucose cotransporter 2(SGLT2)inhibitors and glucagon-like peptide-1(GLP-1)receptor agonists,which were initially developed for hyperglycemia management,have transformed the treatment of obesity,heart failure,cardiovascular disease,and more recently,DKD.SGLT2 inhibitors have consistently and significantly reduced cardiovascular events,albuminuria,and glomerular filtration rate,highlighting their efficacy across diverse clinical presentations for patients with kidney impairment.Although fewer studies have specifically investigated GLP-1 receptor agonists in patients with kidney disease,existing evidence underscores their potential to slow renal disease progression,reduce albuminuria,and improve clinically relevant outcomes.However,further research is needed to better identify patients most likely to benefit from treatment.Together,these therapies represent valuable advancements for DKD,offering significant reductions in morbidity and mortality and shifting the management of the disease by becoming essential pillars for the treatment of these patients.展开更多
BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose c...BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose cotransporter-2 inhibitor(SGLT2i)and/or glucagon like peptide-1 receptor agonists(GLP-1RAs)for renal protection.The real-world efficacy of the two medications on the urinary albumin-creatinine ratio(UACR)and estimated glomerular filtration rate(eGFR)remains to be explored.AIM To evaluate the SGLT2i and GLP-1RA application rates and UACR alterations after intervention in a real-world cohort of patients with diabetes.METHODS A cohort of 5482 patients with type 2 diabetes were enrolled and followed up at the Integrated Care Clinic for Diabetes of Peking University First Hospital for at least 6 months.Propensity score matching was performed,and patients who were not recommended for GLP-1RA or SGLT2i with comparable sex categories and ages were assigned to the control group at a 1:2 ratio.Blood glucose,body weight,UACR and eGFR were evaluated after 6 months of treatment in real-world clinical practice.RESULTS A total of 139(2.54%)patients started GLP-1RA,and 387(7.06%)received SGLT2i.After 6 months,the variations in fasting blood glucose,prandial blood glucose,and glycosylated hemoglobin between the GLP-1RA group and the SGLT2i and control groups were not significantly different.UACR showed a tendency toward a greater reduction compared with the control group,although this difference was not statistically significant(GLP-1RA vs control,-2.20 vs 30.16 mg/g,P=0.812;SGLT2i vs control,-20.61 vs 12.01 mg/g,P=0.327);eGFR alteration also showed no significant differences.Significant weight loss was observed in the GLP-1RA group compared with the control group(GLP-1RA vs control,-0.90 vs 0.27 kg,P<0.001),as well as in the SGLT2i group(SGLT2i vs control,-0.59 vs-0.03 kg,P=0.010).CONCLUSION Compared with patients who received other glucose-lowering drugs,patients receiving SGLT2i or GLP-1RAs presented significant weight loss,a decreasing trend in UACR and comparable glucose-lowering effects in realworld settings.展开更多
Background and Objective:Idiopathic intracranial hypertension(IIH)is a disorder of raised intracranial pressure(ICP)associated with overweight and obesity,with weight loss being the mainstay of management.Diet and lif...Background and Objective:Idiopathic intracranial hypertension(IIH)is a disorder of raised intracranial pressure(ICP)associated with overweight and obesity,with weight loss being the mainstay of management.Diet and lifestyle changes alone are often unsuccessful at achieving meaningful or sustained weight loss.Glucagon-like peptide-1 receptor agonists(GLP-1RA)are a class of medications developed for the treatment of diabetes but are also highly effective for weight reduction.The objective of this narrative review is to present the current evidence for GLP-1RAs in the management of IIH.Methods:Articles were searched for inclusion through OVID using the following terms:[papilledema OR intracranial hypertension OR idiopathic intracranial hypertension OR brain pseudotumor]and[glucagon like peptide 1 OR glucagon like peptide 1 receptor agonist OR semaglutide OR exendin 4 OR liraglutide OR tirzepatide].Titles and abstracts were screened manually for relevance.There were no exclusion criteria for time frame,language,population or article type,although conference abstracts were not included.An illustrative case of a patient with IIH treated with tirzepatide and semaglutide is also presented.Key Content and Findings:GLP-1RAs have demonstrated the potential for significantly greater weight loss in patients with IIH,with a reduced requirement for IIH medications and improved symptoms,compared to conventional weight management.Treatment with GLP-1RAs has also been shown to result in a rapid and persistent reduction in ICP in both rat and human studies.The side effects of GLP-1RAs are generally well-tolerated,with low rates of discontinuation in clinical trials.However,continuous treatment is likely required to avoid weight rebound and symptom recurrence after cessation.Conclusions:Despite highly promising preliminary evidence,further clinical trials are needed to determine the most effective GLP-1RA medications within this class,appropriate dosing regimens and treatment duration.展开更多
Introduction Nonarteritic anterior ischemic optic neuropathy(NAION)is the most common acute optic neuropathy in patients over the age of 50 years(1).It is characterized by acute,painless vision loss in one eye which i...Introduction Nonarteritic anterior ischemic optic neuropathy(NAION)is the most common acute optic neuropathy in patients over the age of 50 years(1).It is characterized by acute,painless vision loss in one eye which is often noticed upon awakening.Commonly,there is an altitudinal visual field defect,though this can be variable(1).展开更多
BACKGROUND Data on the use of glucagon-like peptide-1 receptor agonists(GLP-1RAs)in individuals with type 2 diabetes mellitus(T2DM)during Ramadan fasting is limited.No meta-analysis has summarized the safety and effec...BACKGROUND Data on the use of glucagon-like peptide-1 receptor agonists(GLP-1RAs)in individuals with type 2 diabetes mellitus(T2DM)during Ramadan fasting is limited.No meta-analysis has summarized the safety and effectiveness of GLP-1RAs in these situations.AIM To evaluate the safety and efficacy of GLP-1RA in patients with T2DM fasting during Ramadan.METHODS Electronic databases were systematically searched for relevant studies that featured GLP-1RA in the intervention arm and other glucose-lowering medications in the control arm.The primary outcome was adverse events(AEs)during Ramadan for both groups;other outcomes included changes in glycemic and anthropometric measures during the peri-Ramadan period.RESULTS Four studies[three randomized-controlled trials with low risk of bias(RoB)and one prospective observational study with serious RoB]involving 754 subjects were analyzed.GLP-1RA group achieved greater glycated hemoglobin reduction than the non-GLP-1RA group[mean difference(MD):-0.31%,95%CI:-0.61 to-0.01,P=0.04,I2=77%]with a lower risk of documented symptomatic hypoglycemia(risk ratio=0.38,95%CI:0.16 to 0.88,P=0.02).Any AEs,serious AEs,or AEs that led to treatment discontinuation were comparable between the two groups.The GLP-1RA group experienced greater weight loss compared to the non-GLP-1RA group(MD:-2.0 kg,95%CI:-3.37 to-0.63,P=0.004,I2=95%).There were comparable changes in blood pressure and lipid profile between the two groups.GLP-1RA users experienced higher risks of gastrointestinal AEs,nausea,and vomiting;however,the risks of heartburn,abdominal pain,and diarrhea were similar in both groups.CONCLUSION Limited evidence suggests that GLP-1RAs are safe for T2DM management during Ramadan,offering modest benefits in blood sugar control and weight loss.Large multicenter trials are needed to confirm their safety and efficacy in at-risk populations,improving clinical practice decision-making.展开更多
Prostate cancer is a leading cause of cancer-related death in men worldwide.Luteinizing hormone-releasing hormone receptor(LHRH-R)agonists and antagonists are known to achieve castration-level testosterone suppression...Prostate cancer is a leading cause of cancer-related death in men worldwide.Luteinizing hormone-releasing hormone receptor(LHRH-R)agonists and antagonists are known to achieve castration-level testosterone suppression;however,long-term data comparing the survival benefits of these therapies are insufficient to inform treatment decisions.Furthermore,the advent of nextgeneration hormonal agents(NHAs),such as abiraterone and enzalutamide,have shifted the paradigm of managing prostate cancer.Although LHRH-R agonists and antagonists remain the cornerstone treatment across various stages of prostate cancer,they are increasingly administered with NHAs,because the combination treatment confers a survival advantage.Nevertheless,the differences in efficacy and safety profiles among various combinations of LHRH-R agonists and antagonists and NHAs remain unclear.Hence,this narrative review is aimed at providing a comprehensive overview of the long-term outcomes of various LHRH-R agonists and antagonists.Key data from major clinical studies are summarized,categorized by disease stage.LHRH-R agonists and antagonists,particularly goserelin,have demonstrated long-term survival benefits in patients with localized and locally advanced prostate cancer.The clinical outcomes of different LHRH-R agonists and antagonists in combination with NHAs have also been evaluated.Among the various combinations,goserelin plus abiraterone appears to have a manageable safety profile with relatively low rates of hot flushes and fatigue.Overall,long-term survival data and safety profiles should be considered in selecting optimal combination therapies for prostate cancer treatment.展开更多
Human nAChR u7 is the potential target for schizophrenia cognitive disorders, and it is meaningful to develop selective human nAChR α7 agonists for the clinical treatment of the disease. Because the crystal structure...Human nAChR u7 is the potential target for schizophrenia cognitive disorders, and it is meaningful to develop selective human nAChR α7 agonists for the clinical treatment of the disease. Because the crystal structure ofα7 receptor has not been resolved, ligand-based drug design strategy was took in this work. A 3D QSAR pharmacophore model was built by HypoGen method, and its quality was evaluated by cost function. Furthermore, the pharmacophore model was validated with activity prediction of test set and was cross-validated based on Fisher＇s Randomization Method. By Enrichment Factor and AU-ROC analysis, the final pharmacophore, which is consisted of one HBA, two Hydrophobic and one PosIonizable, was selected and it fitted well with the docking result of α7 homology model and the ligand. The pharmacophore is expected for the following virtual screening and lead optimization of human nAChR α7 agonists, which is important for the development and discovery of novel antipsychotics.展开更多
Abscisic acid(ABA),a plant hormone,is crucial for regulating various physiological and developmental processes in plants,including adaptation to biotic and abiotic stresses.Recent advancements have significantly contr...Abscisic acid(ABA),a plant hormone,is crucial for regulating various physiological and developmental processes in plants,including adaptation to biotic and abiotic stresses.Recent advancements have significantly contributed to our understanding of ABA's biosynthetic pathway,transport,signaling pathway,and metabolism.To overcome the limitations of natural ABA,scientists have developed broad-spectrum and highly active agonists of ABA receptors.However,the practical application of these receptor agonists as agrochemicals still faces several challenges.On the other hand,some ABA antagonists have also been developed to differentiate the functional differences among various receptors more accurately.This can help design ABA agonists that can selectively activate specific physiological responses,thereby eliminating the undesired physiological effects induced by ABA.This paper aims to provide a comprehensive overview of the current ABA receptor agonists and antagonists to assist in developing novel ABA functional analogs with improved efficacy and simpler chemical structures that are suitable for agricultural applications.展开更多
Glucagon-like peptide1 (GLP-1) is secreted from Langerhans cells in response to oral nutrient intake. Glucagon- like peptide-1 receptor agonists (GLP-1RAs) are a new class of incretin-based anti-diabetic drugs. They f...Glucagon-like peptide1 (GLP-1) is secreted from Langerhans cells in response to oral nutrient intake. Glucagon- like peptide-1 receptor agonists (GLP-1RAs) are a new class of incretin-based anti-diabetic drugs. They function to stimulate insulin secretion while suppressing glucagon secretion. GLP-1-based therapies are now well established in the management of type 2 diabetes mellitus (T2DM), and recent literature has suggested potential applications of these drugs in the treatment of obesity and for protection against cardiovascular and neurological diseases. As we know, along with change in lifestyles, the prevalence of non-alcoholic fatty liver disease (NAFLD) in China is rising more than that of viral hepatitis and alcoholic fatty liver disease, and NAFLD has become the most common chronic liver disease in recent years. Recent studies further suggest that GLP-1RAs can reduce transaminase levels to improve NAFLD by improving blood lipid levels, cutting down the fat content to promote fat redistribution, directly decreasing fatty degeneration of the liver, reducing the degree of liver fibrosis and improving inflammation. This review shows the NAFLD-associated effects of GLP-1RAs in animal models and in patients with T2DM or obesity who are participants in clinical trials. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.展开更多
To discover new lead compounds for M1 agonists. Ten typical M1 agonists were superimposed to build a M1 agonists 3D-pharmacophore model using distance-comparisons （DISCO） method without the previous knowledge of the...To discover new lead compounds for M1 agonists. Ten typical M1 agonists were superimposed to build a M1 agonists 3D-pharmacophore model using distance-comparisons （DISCO） method without the previous knowledge of the three-dimensional structure of M1 receptor. Virtual screening strategy was used to analyze the Available Chemicals Directory-Screening Compounds （ACD-SC） to identify possible new hits. Twenty-two compounds which fit the pharmacophore model well and are not similar with known M1 agonists were purchased in order to evaluate their M1 receptor agonist activity. One of them shows M1 receptor agonist activity with EC50 of 4.90 μmol/L and maximum response. Multiple of 10.0 which shows it worthy of further study as a new lead compound for M1 agonists.展开更多
Glucagon-like peptide-1(GLP-1)receptor agonists result in greater improvements in glycemic control than placebo and promote weight loss with minimal hypoglycemia in patients with type 2 diabetes mellitus.A number of c...Glucagon-like peptide-1(GLP-1)receptor agonists result in greater improvements in glycemic control than placebo and promote weight loss with minimal hypoglycemia in patients with type 2 diabetes mellitus.A number of case reports show an association of GLP-1receptor agonists,mainly exenatide,with the development of acute kidney injury.The present review aims to present the available data regarding the effects of GLP-1 receptor agonists on renal function,their use in subjects with chronic renal failure and their possible association with acute kidney injury.Based on the current evidence,exenatide is eliminated by renal mechanisms and should not be given in patients with severe renal impairment or end stage renal disease.Liraglutide is not eliminated by renal or hepatic mechanisms,but it should be used with caution since there are only limited data in patients with renal or hepatic impairment.There is evidence from animal studies that GLP-1 receptor agonists exert protective role in diabetic nephropathy with mechanisms that seem to be independent of their glucose-lowering effect.Additionally,there is evidence that GLP-1 receptor agonists influence water and electrolyte balance.These effects may represent new ways to improve or even prevent diabetic nephropathy.展开更多
Nonalcoholic fatty liver disease(NAFLD) is highly associated with insulin resistance(IR), type 2 diabetes mellitus and metabolic syndrome, being characterized as the hepatic component of metabolic syndrome. Despite it...Nonalcoholic fatty liver disease(NAFLD) is highly associated with insulin resistance(IR), type 2 diabetes mellitus and metabolic syndrome, being characterized as the hepatic component of metabolic syndrome. Despite its high prevalence, no pharmacological treatment has been established, as of yet. A growing body of evidence, however, shows that reducing IR can result in improvement of the biochemical and histological features of nonalcoholic steatohepatitis(NASH)-the aggressive form of NAFLD that can lead to cirrhosis and hepatocellular carcinoma. Unfortunately, the several trials that have assessed the effect of various antidiabetic agents to date have failed to establish an effective and safe treatment regimen for patients with NAFLD. Glucagon-like peptide-1(commonly known as GLP-1) agonists are a novel class of antidiabetic drugs that improve insulin sensitivity and promote weight loss. They also appear to have a direct effect on the lipid metabolism of hepatocytes, reducing hepatic steatosis. Several trials have demonstrated that GLP-1 agonists can reduce aminotransferase levels and improve liver histology in patients with NAFLD, suggesting that these agents could serve as an alternative treatment option for these patients. This manuscript discusses the role and potential mechanisms of GLP-1 agonists in the treatment of NASH.展开更多
Non-alcoholic fatty liver disease(NAFLD)is the predominant cause of chronic liver disease worldwide.NAFLD progresses in some cases to non-alcoholic steatohepatitis(NASH),which is characterized,in addition to liver fat...Non-alcoholic fatty liver disease(NAFLD)is the predominant cause of chronic liver disease worldwide.NAFLD progresses in some cases to non-alcoholic steatohepatitis(NASH),which is characterized,in addition to liver fat deposition,by hepatocyte ballooning,inflammation and liver fibrosis,and in some cases may lead to hepatocellular carcinoma.NAFLD prevalence increases along with the rising incidence of type 2 diabetes mellitus(T2DM).Currently,lifestyle interventions and weight loss are used as the major therapeutic strategy in the vast majority of patients with NAFLD.Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are used in the management of T2DM and do not have major side effects like hypoglycemia.In patients with NAFLD,the GLP-1 receptor production is down-regulated.Recently,several animal and human studies have emphasized the role of GLP-1RAs in ameliorating liver fat accumulation,alleviating the inflammatory environment and preventing NAFLD progression to NASH.In this review,we summarize the updated literature data on the beneficial effects of GLP-1RAs in NAFLD/NASH.Finally,as GLP-1RAs seem to be an attractive therapeutic option for T2DM patients with concomitant NAFLD,we discuss whether GLP-1RAs should represent the first line pharmacotherapy for these patients.展开更多
Chronic kidney disease constitutes a major microvascular complication of diabetes mellitus.Accumulating data suggest that glucagon-like peptide-1 receptor agonists(GLP-1 RAs)might have a role in the management of diab...Chronic kidney disease constitutes a major microvascular complication of diabetes mellitus.Accumulating data suggest that glucagon-like peptide-1 receptor agonists(GLP-1 RAs)might have a role in the management of diabetic kidney disease(DKD).GLP-1 RAs appear to reduce the incidence of persistent macro-albuminuria in patients with type 2 diabetes mellitus.This beneficial effect appears to be mediated not only by the glucose-lowering action of these agents but also on their blood pressure lowering,anti-inflammatory and antioxidant effects.On the other hand,GLP-1 RAs do not appear to affect the rate of decline of glomerular filtration rate.However,this might be due to the relatively short duration of the trials that evaluated their effects on DKD.Moreover,these trials were not designed nor powered to assess renal outcomes.Given than macrolbuminuria is a strong risk factor for the progression of DKD,it might be expected that GLP-1 RAs will prevent the deterioration in renal function in the long term.Nevertheless,this remains to be shown in appropriately designed randomized controlled trials in patients with DKD.展开更多
文摘This article comments on the work by Soresi and Giannitrapani.The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease(MASLD)is the use of glucagon-like peptide 1 receptor agonists,especially when used in combination therapy.However,despite their notable efficacy,these drugs were not initially designed to target MASLD directly.In a groundbreaking development,the Food and Drug Administration has recently approved resmetirom,the first treatment specifically aimed at reducing liver fibrosis in metabolic-associated steatohepatitis.Resmetirom,an orally administered,liver-directed thyroid hormone beta-selective agonist,acts directly on intrahepatic pathways,enhancing its therapeutic potential and marking the beginning of a new era in the treatment of MASLD.Furthermore,the integration of lifestyle modifications into liver disease management is an essential component that should be considered and reinforced.By incorporating dietary changes and regular physical exercise into treatment,patients may achieve improved outcomes,reducing the need for pharmacological interventions and/or improving treatment efficacy.As a complement to medical therapies,lifestyle factors should not be overlooked in the broader strategy for managing MASLD.
文摘Glucagon-like peptide-1 (GLP-1) and its receptor agonists (GLP-1RAs) are wellestablishedtherapies for metabolic conditions such as type 2 diabetes and obesitydue to their ability to enhance insulin secretion, promote weight loss, and regulateblood glucose levels. Emerging evidence, however, indicates that GLP-1RAs mayalso have therapeutic potential in inflammatory and autoimmune conditions. Thisreview explores the evolving role of GLP-1RAs in managing rheumatic diseases,including osteoarthritis, rheumatoid arthritis, psoriatic arthritis, and systemiclupus erythematosus. Studies suggest that GLP-1RAs reduce inflammation bymodulating immune cell activity, increasing anti-inflammatory cytokine production,shifting macrophage polarization toward an anti-inflammatory phenotype,and enhancing regulatory T-cell function to maintain immune homeostasis. Theseimmunomodulatory effects point toward a promising adjunctive strategy incurrent clinical practice for patients with rheumatic diseases, particularly thosewith metabolic comorbidities. Further clinical trials are warranted to validatethese findings, clarify underlying mechanisms, and assess long-term safety,ultimately paving the way for novel treatment approaches in rheumatology.
文摘BACKGROUND Atrial fibrillation(AF)stands as the most prevalent type of arrhythmia,affecting approximately 60 million individuals world-wide.Although antiarrhythmic drugs(AADs)remain the gold standard for AF treatment,glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are arising as potential therapeutic alternatives.AIM To evaluate the impact of GLP-1 RAs on the incidence of AF.METHODS Inclusion criteria included systematic reviews(SRs)that based their analyses on clinical trials,observational studies,controlled trials and network meta-analyses.A total of 8 SRs were selected for data extraction,focusing on semaglutide,liraglutide and dulaglutide.Additionally,the effects of GLP-1 RAs on AF incidence were compared with those of sodium-glucose co-transporter 2(SGLT2)inhibitors.RESULTS Findings indicate that semaglutide,evaluated in the largest patient cohort across the 8 SRs,consistently reduced AF incidence.However,dulaglutide and liraglutide exhibited inconsistent effects.Notably,as opposed to variable outcomes associated with GLP-1 RAs,SGLT2 inhibitors a class of antidiabetic agents with weight-reducing properties exhibit significant cardiovascular benefits,including reductions in both AF and atrial flutter.CONCLUSION GLP-1 RAs emerge as a promising and potential alternative for AADs in reduction of incidence of AF.However,further research is required to fully determine their therapeutic potential and long-term cardiovascular effects.
文摘Obesity is a global pandemic that has been threatening the worldwide population.It has been reported to be associated with an increase in the risk of chronic diseases such as type 2 diabetes mellitus(T2DM),cardiovascular disease,and other diseases,including some malignancies.Currently,the first line of management includes lifestyle modifications.However,recently,bariatric surgeries were introduced to combat obesity.The previous modalities of management are always challenging since lifestyle could have limited long-term effectiveness and difficulty to achieve,and surgeries are invasive and also require a lifestyle modification and commitment.Glucagon-like peptide-1 receptor agonists(GLP-1RAs)were initially introduced as a rising star for managing T2DM,with patients benefiting from the control of blood sugar and weight loss.These medications work by enhancing feelings of fullness,slowing down digestion,and ultimately reducing calorie intake.However,GLP-1RAs are not without side effects and have some costs.Common side effects include gastrointestinal(GI)adverse events such as nausea,vomiting,diarrhea,and a lack of GI motility,which is the main mechanism through which the drug induces a feeling of fullness and promotes weight loss,potentially resulting in treatment discontinuation.More serious,though less frequent,risks include pancreatitis,gallbladder diseases,and,rarely,thyroid Ccell cancers.This review aimed to discuss the globally emerging role of GLP-1RAs in obesity management and highlight some safety considerations for patients taking these drugs.
文摘BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RAs)play a key role in managing type 2 diabetes mellitus(T2DM).Transitioning between different GLP-1RA has been proposed as a treatment strategy.AIM To investigate switching patterns between GLP-1RA and their impact on glycemic control.METHODS A retrospective study involving patients with T2DM who initiated GLP-1RA therapy between 2009 and 2021 and transitioned to another GLP-1RA.Baseline glycated hemoglobin(HbA1c)was defined as the most recent measurement within 1 year prior to switching,and follow-up HbA1c was the first measurement recorded 4-15 months post-switch.RESULTS Among 70654 patients initiating GLP-1RA therapy,18047(25.5%)switched regimens.In the 13970 patients with available HbA1c,levels decreased from 8.5%±1.6%to 7.6%±1.4%(P<0.001).HbA1c decreased in 78.3%(10943/13970)of these patients,with the most frequent improvement observed in those switching from daily to weekly GLP-1RA(81%,5582/6890).CONCLUSION Switching between GLP-1RAs can serve as a practical alternative to treatment intensification for effectively managing T2DM.
文摘BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are increasingly being used to treat type 2 diabetes mellitus(T2DM)and obesity.Although GLP-1RAs delay gastric emptying,their impact on gastric mucosal visibility during upper endoscopy remains uncertain,especially in Asian patients.AIM To investigate the association between GLP-1RA treatment and gastric mucosal visibility during upper endoscopy in Asian patients with T2DM.METHODS The study population included Korean patients who underwent esophagogastroduodenoscopy(EGD)with concomitant GLP-1RA or dipeptidyl peptidase 4 inhibitor(DPP4i)for the treatment of T2DM.A 1:2 propensity score matching between GLP-1RA and DPP4i users resulted in 198 matched patients and 295 matched patients in each group,respectively.Gastric mucosal visibility was assessed by reviewing endoscopy images with a validated scale(POLPREP).In addition,the rates of aborted and repeat EGD and pulmonary aspiration were also assessed.RESULTS Of the 493 matched patients,mean body mass index was 26.0 kg/m^(2).The rate of inadequate gastric mucosal visibility(gastric POLPREP score 0 or 1)was significantly higher in GLP-1RA group than matched DPP4i group(8.6%vs 1.4%,P=0.0007).The rates of aborted EGD and repeat EGD were also significantly higher in GLP-1RA than DPP4i group(7.6%vs 0.7%in both aborted and repeat EGD,P=0.0011).Multivariable logistic regression revealed GLP-1RA use as an independent risk factor for both inadequate gastric mucosal visibility(odds ratio=6.143,95%confidence interval:2.289,20.318,P=0.0008)and aborted EGD(odds ratio=11.099,95%confidence interval:3.172,63.760,P=0.0010).Despite gastric residue,no pulmonary aspiration was reported in either group.CONCLUSION GLP-1RA use was associated with a higher risk of inadequate gastric mucosal visibility and aborted and repeat procedures during upper gastrointestinal endoscopy in Korean patients with T2DM while pulmonary aspiration was not observed.
基金Supported by Industrial Technological Initiation Scholarship of National Council for Scientific and Technological Development,CNPq,Brazil,No.0932204294929829 and No.7414780530977345the Scientific Initiation Scholarship Programme(PIBIC)of National Council for Scientific and Technological Development,CNPq,Brazil,No.5763023359532159,No.6472982965854452,and No.7340128440641417the CNPq Research Productivity Fellow,No.4357511882624145.
文摘The global prevalence of diabetes has surged in recent years,with diabetic kidney disease(DKD)emerging as a major complication.Traditional therapies have had limited success in slowing progression to end-stage kidney disease.However,novel therapies,particularly sodium-glucose cotransporter 2(SGLT2)inhibitors and glucagon-like peptide-1(GLP-1)receptor agonists,which were initially developed for hyperglycemia management,have transformed the treatment of obesity,heart failure,cardiovascular disease,and more recently,DKD.SGLT2 inhibitors have consistently and significantly reduced cardiovascular events,albuminuria,and glomerular filtration rate,highlighting their efficacy across diverse clinical presentations for patients with kidney impairment.Although fewer studies have specifically investigated GLP-1 receptor agonists in patients with kidney disease,existing evidence underscores their potential to slow renal disease progression,reduce albuminuria,and improve clinically relevant outcomes.However,further research is needed to better identify patients most likely to benefit from treatment.Together,these therapies represent valuable advancements for DKD,offering significant reductions in morbidity and mortality and shifting the management of the disease by becoming essential pillars for the treatment of these patients.
基金Peking University First Hospital Institutional Review Board(No.2018104).
文摘BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose cotransporter-2 inhibitor(SGLT2i)and/or glucagon like peptide-1 receptor agonists(GLP-1RAs)for renal protection.The real-world efficacy of the two medications on the urinary albumin-creatinine ratio(UACR)and estimated glomerular filtration rate(eGFR)remains to be explored.AIM To evaluate the SGLT2i and GLP-1RA application rates and UACR alterations after intervention in a real-world cohort of patients with diabetes.METHODS A cohort of 5482 patients with type 2 diabetes were enrolled and followed up at the Integrated Care Clinic for Diabetes of Peking University First Hospital for at least 6 months.Propensity score matching was performed,and patients who were not recommended for GLP-1RA or SGLT2i with comparable sex categories and ages were assigned to the control group at a 1:2 ratio.Blood glucose,body weight,UACR and eGFR were evaluated after 6 months of treatment in real-world clinical practice.RESULTS A total of 139(2.54%)patients started GLP-1RA,and 387(7.06%)received SGLT2i.After 6 months,the variations in fasting blood glucose,prandial blood glucose,and glycosylated hemoglobin between the GLP-1RA group and the SGLT2i and control groups were not significantly different.UACR showed a tendency toward a greater reduction compared with the control group,although this difference was not statistically significant(GLP-1RA vs control,-2.20 vs 30.16 mg/g,P=0.812;SGLT2i vs control,-20.61 vs 12.01 mg/g,P=0.327);eGFR alteration also showed no significant differences.Significant weight loss was observed in the GLP-1RA group compared with the control group(GLP-1RA vs control,-0.90 vs 0.27 kg,P<0.001),as well as in the SGLT2i group(SGLT2i vs control,-0.59 vs-0.03 kg,P=0.010).CONCLUSION Compared with patients who received other glucose-lowering drugs,patients receiving SGLT2i or GLP-1RAs presented significant weight loss,a decreasing trend in UACR and comparable glucose-lowering effects in realworld settings.
文摘Background and Objective:Idiopathic intracranial hypertension(IIH)is a disorder of raised intracranial pressure(ICP)associated with overweight and obesity,with weight loss being the mainstay of management.Diet and lifestyle changes alone are often unsuccessful at achieving meaningful or sustained weight loss.Glucagon-like peptide-1 receptor agonists(GLP-1RA)are a class of medications developed for the treatment of diabetes but are also highly effective for weight reduction.The objective of this narrative review is to present the current evidence for GLP-1RAs in the management of IIH.Methods:Articles were searched for inclusion through OVID using the following terms:[papilledema OR intracranial hypertension OR idiopathic intracranial hypertension OR brain pseudotumor]and[glucagon like peptide 1 OR glucagon like peptide 1 receptor agonist OR semaglutide OR exendin 4 OR liraglutide OR tirzepatide].Titles and abstracts were screened manually for relevance.There were no exclusion criteria for time frame,language,population or article type,although conference abstracts were not included.An illustrative case of a patient with IIH treated with tirzepatide and semaglutide is also presented.Key Content and Findings:GLP-1RAs have demonstrated the potential for significantly greater weight loss in patients with IIH,with a reduced requirement for IIH medications and improved symptoms,compared to conventional weight management.Treatment with GLP-1RAs has also been shown to result in a rapid and persistent reduction in ICP in both rat and human studies.The side effects of GLP-1RAs are generally well-tolerated,with low rates of discontinuation in clinical trials.However,continuous treatment is likely required to avoid weight rebound and symptom recurrence after cessation.Conclusions:Despite highly promising preliminary evidence,further clinical trials are needed to determine the most effective GLP-1RA medications within this class,appropriate dosing regimens and treatment duration.
文摘Introduction Nonarteritic anterior ischemic optic neuropathy(NAION)is the most common acute optic neuropathy in patients over the age of 50 years(1).It is characterized by acute,painless vision loss in one eye which is often noticed upon awakening.Commonly,there is an altitudinal visual field defect,though this can be variable(1).
基金thankful to Dr.Marina George Kudiyirickal MSc,MJDF-RCS,PhD for providing us the audio core tip of this article.
文摘BACKGROUND Data on the use of glucagon-like peptide-1 receptor agonists(GLP-1RAs)in individuals with type 2 diabetes mellitus(T2DM)during Ramadan fasting is limited.No meta-analysis has summarized the safety and effectiveness of GLP-1RAs in these situations.AIM To evaluate the safety and efficacy of GLP-1RA in patients with T2DM fasting during Ramadan.METHODS Electronic databases were systematically searched for relevant studies that featured GLP-1RA in the intervention arm and other glucose-lowering medications in the control arm.The primary outcome was adverse events(AEs)during Ramadan for both groups;other outcomes included changes in glycemic and anthropometric measures during the peri-Ramadan period.RESULTS Four studies[three randomized-controlled trials with low risk of bias(RoB)and one prospective observational study with serious RoB]involving 754 subjects were analyzed.GLP-1RA group achieved greater glycated hemoglobin reduction than the non-GLP-1RA group[mean difference(MD):-0.31%,95%CI:-0.61 to-0.01,P=0.04,I2=77%]with a lower risk of documented symptomatic hypoglycemia(risk ratio=0.38,95%CI:0.16 to 0.88,P=0.02).Any AEs,serious AEs,or AEs that led to treatment discontinuation were comparable between the two groups.The GLP-1RA group experienced greater weight loss compared to the non-GLP-1RA group(MD:-2.0 kg,95%CI:-3.37 to-0.63,P=0.004,I2=95%).There were comparable changes in blood pressure and lipid profile between the two groups.GLP-1RA users experienced higher risks of gastrointestinal AEs,nausea,and vomiting;however,the risks of heartburn,abdominal pain,and diarrhea were similar in both groups.CONCLUSION Limited evidence suggests that GLP-1RAs are safe for T2DM management during Ramadan,offering modest benefits in blood sugar control and weight loss.Large multicenter trials are needed to confirm their safety and efficacy in at-risk populations,improving clinical practice decision-making.
文摘Prostate cancer is a leading cause of cancer-related death in men worldwide.Luteinizing hormone-releasing hormone receptor(LHRH-R)agonists and antagonists are known to achieve castration-level testosterone suppression;however,long-term data comparing the survival benefits of these therapies are insufficient to inform treatment decisions.Furthermore,the advent of nextgeneration hormonal agents(NHAs),such as abiraterone and enzalutamide,have shifted the paradigm of managing prostate cancer.Although LHRH-R agonists and antagonists remain the cornerstone treatment across various stages of prostate cancer,they are increasingly administered with NHAs,because the combination treatment confers a survival advantage.Nevertheless,the differences in efficacy and safety profiles among various combinations of LHRH-R agonists and antagonists and NHAs remain unclear.Hence,this narrative review is aimed at providing a comprehensive overview of the long-term outcomes of various LHRH-R agonists and antagonists.Key data from major clinical studies are summarized,categorized by disease stage.LHRH-R agonists and antagonists,particularly goserelin,have demonstrated long-term survival benefits in patients with localized and locally advanced prostate cancer.The clinical outcomes of different LHRH-R agonists and antagonists in combination with NHAs have also been evaluated.Among the various combinations,goserelin plus abiraterone appears to have a manageable safety profile with relatively low rates of hot flushes and fatigue.Overall,long-term survival data and safety profiles should be considered in selecting optimal combination therapies for prostate cancer treatment.
基金National Natural Science Foundation of China(Grant No.81373272)
文摘Human nAChR u7 is the potential target for schizophrenia cognitive disorders, and it is meaningful to develop selective human nAChR α7 agonists for the clinical treatment of the disease. Because the crystal structure ofα7 receptor has not been resolved, ligand-based drug design strategy was took in this work. A 3D QSAR pharmacophore model was built by HypoGen method, and its quality was evaluated by cost function. Furthermore, the pharmacophore model was validated with activity prediction of test set and was cross-validated based on Fisher＇s Randomization Method. By Enrichment Factor and AU-ROC analysis, the final pharmacophore, which is consisted of one HBA, two Hydrophobic and one PosIonizable, was selected and it fitted well with the docking result of α7 homology model and the ligand. The pharmacophore is expected for the following virtual screening and lead optimization of human nAChR α7 agonists, which is important for the development and discovery of novel antipsychotics.
基金supported by the National Natural Science Foundation of China(No.22077136).
文摘Abscisic acid(ABA),a plant hormone,is crucial for regulating various physiological and developmental processes in plants,including adaptation to biotic and abiotic stresses.Recent advancements have significantly contributed to our understanding of ABA's biosynthetic pathway,transport,signaling pathway,and metabolism.To overcome the limitations of natural ABA,scientists have developed broad-spectrum and highly active agonists of ABA receptors.However,the practical application of these receptor agonists as agrochemicals still faces several challenges.On the other hand,some ABA antagonists have also been developed to differentiate the functional differences among various receptors more accurately.This can help design ABA agonists that can selectively activate specific physiological responses,thereby eliminating the undesired physiological effects induced by ABA.This paper aims to provide a comprehensive overview of the current ABA receptor agonists and antagonists to assist in developing novel ABA functional analogs with improved efficacy and simpler chemical structures that are suitable for agricultural applications.
文摘Glucagon-like peptide1 (GLP-1) is secreted from Langerhans cells in response to oral nutrient intake. Glucagon- like peptide-1 receptor agonists (GLP-1RAs) are a new class of incretin-based anti-diabetic drugs. They function to stimulate insulin secretion while suppressing glucagon secretion. GLP-1-based therapies are now well established in the management of type 2 diabetes mellitus (T2DM), and recent literature has suggested potential applications of these drugs in the treatment of obesity and for protection against cardiovascular and neurological diseases. As we know, along with change in lifestyles, the prevalence of non-alcoholic fatty liver disease (NAFLD) in China is rising more than that of viral hepatitis and alcoholic fatty liver disease, and NAFLD has become the most common chronic liver disease in recent years. Recent studies further suggest that GLP-1RAs can reduce transaminase levels to improve NAFLD by improving blood lipid levels, cutting down the fat content to promote fat redistribution, directly decreasing fatty degeneration of the liver, reducing the degree of liver fibrosis and improving inflammation. This review shows the NAFLD-associated effects of GLP-1RAs in animal models and in patients with T2DM or obesity who are participants in clinical trials. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
基金National Natural Science Foundation of China (Grant No. 30271538)985 program,Ministry of Education of China
文摘To discover new lead compounds for M1 agonists. Ten typical M1 agonists were superimposed to build a M1 agonists 3D-pharmacophore model using distance-comparisons （DISCO） method without the previous knowledge of the three-dimensional structure of M1 receptor. Virtual screening strategy was used to analyze the Available Chemicals Directory-Screening Compounds （ACD-SC） to identify possible new hits. Twenty-two compounds which fit the pharmacophore model well and are not similar with known M1 agonists were purchased in order to evaluate their M1 receptor agonist activity. One of them shows M1 receptor agonist activity with EC50 of 4.90 μmol/L and maximum response. Multiple of 10.0 which shows it worthy of further study as a new lead compound for M1 agonists.
文摘Glucagon-like peptide-1(GLP-1)receptor agonists result in greater improvements in glycemic control than placebo and promote weight loss with minimal hypoglycemia in patients with type 2 diabetes mellitus.A number of case reports show an association of GLP-1receptor agonists,mainly exenatide,with the development of acute kidney injury.The present review aims to present the available data regarding the effects of GLP-1 receptor agonists on renal function,their use in subjects with chronic renal failure and their possible association with acute kidney injury.Based on the current evidence,exenatide is eliminated by renal mechanisms and should not be given in patients with severe renal impairment or end stage renal disease.Liraglutide is not eliminated by renal or hepatic mechanisms,but it should be used with caution since there are only limited data in patients with renal or hepatic impairment.There is evidence from animal studies that GLP-1 receptor agonists exert protective role in diabetic nephropathy with mechanisms that seem to be independent of their glucose-lowering effect.Additionally,there is evidence that GLP-1 receptor agonists influence water and electrolyte balance.These effects may represent new ways to improve or even prevent diabetic nephropathy.
文摘Nonalcoholic fatty liver disease(NAFLD) is highly associated with insulin resistance(IR), type 2 diabetes mellitus and metabolic syndrome, being characterized as the hepatic component of metabolic syndrome. Despite its high prevalence, no pharmacological treatment has been established, as of yet. A growing body of evidence, however, shows that reducing IR can result in improvement of the biochemical and histological features of nonalcoholic steatohepatitis(NASH)-the aggressive form of NAFLD that can lead to cirrhosis and hepatocellular carcinoma. Unfortunately, the several trials that have assessed the effect of various antidiabetic agents to date have failed to establish an effective and safe treatment regimen for patients with NAFLD. Glucagon-like peptide-1(commonly known as GLP-1) agonists are a novel class of antidiabetic drugs that improve insulin sensitivity and promote weight loss. They also appear to have a direct effect on the lipid metabolism of hepatocytes, reducing hepatic steatosis. Several trials have demonstrated that GLP-1 agonists can reduce aminotransferase levels and improve liver histology in patients with NAFLD, suggesting that these agents could serve as an alternative treatment option for these patients. This manuscript discusses the role and potential mechanisms of GLP-1 agonists in the treatment of NASH.
文摘Non-alcoholic fatty liver disease(NAFLD)is the predominant cause of chronic liver disease worldwide.NAFLD progresses in some cases to non-alcoholic steatohepatitis(NASH),which is characterized,in addition to liver fat deposition,by hepatocyte ballooning,inflammation and liver fibrosis,and in some cases may lead to hepatocellular carcinoma.NAFLD prevalence increases along with the rising incidence of type 2 diabetes mellitus(T2DM).Currently,lifestyle interventions and weight loss are used as the major therapeutic strategy in the vast majority of patients with NAFLD.Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are used in the management of T2DM and do not have major side effects like hypoglycemia.In patients with NAFLD,the GLP-1 receptor production is down-regulated.Recently,several animal and human studies have emphasized the role of GLP-1RAs in ameliorating liver fat accumulation,alleviating the inflammatory environment and preventing NAFLD progression to NASH.In this review,we summarize the updated literature data on the beneficial effects of GLP-1RAs in NAFLD/NASH.Finally,as GLP-1RAs seem to be an attractive therapeutic option for T2DM patients with concomitant NAFLD,we discuss whether GLP-1RAs should represent the first line pharmacotherapy for these patients.
文摘Chronic kidney disease constitutes a major microvascular complication of diabetes mellitus.Accumulating data suggest that glucagon-like peptide-1 receptor agonists(GLP-1 RAs)might have a role in the management of diabetic kidney disease(DKD).GLP-1 RAs appear to reduce the incidence of persistent macro-albuminuria in patients with type 2 diabetes mellitus.This beneficial effect appears to be mediated not only by the glucose-lowering action of these agents but also on their blood pressure lowering,anti-inflammatory and antioxidant effects.On the other hand,GLP-1 RAs do not appear to affect the rate of decline of glomerular filtration rate.However,this might be due to the relatively short duration of the trials that evaluated their effects on DKD.Moreover,these trials were not designed nor powered to assess renal outcomes.Given than macrolbuminuria is a strong risk factor for the progression of DKD,it might be expected that GLP-1 RAs will prevent the deterioration in renal function in the long term.Nevertheless,this remains to be shown in appropriately designed randomized controlled trials in patients with DKD.
