Glucagon-like peptide 1 agonists are potentially useful drugs for treating metabolic dysfunction-associated steatotic liver disease

In this editorial,we comment on Yin et al’s recently published Letter to the editor.In particular,we focus on the potential use of glucagon-like peptide 1 receptor agonists(GLP-1RAs)alone,but even more so in combination therapy,as one of the most promising therapies in metabolic dysfunction-associated steatotic liver disease(MASLD),the new definition of an old condition,non-alcoholic fatty liver disease,which aims to better define the spectrum of steatotic pathology.It is well known that GLP-1RAs,having shown outstanding performance in fat loss,weight loss,and improvement of insulin resistance,could play a role in protecting the liver from progressive damage.Several clinical trials have shown that,among GLP-1RAs,semaglutide is a safe,well-studied therapeutic choice for MASLD patients;however,most studies demonstrate that,while semaglutide can reduce steatosis,including steatohepatitis histological signs(in terms of inflammatory cell infiltration and hepatocyte ballooning),it does not improve fibrosis.Combinations of therapies with different but complementary mechanisms of action are considered the best way to improve efficiency and slow disease progression due to the complex pathophysiology of the disease.In particular,GLP-1RAs associated with antifibrotic drug therapy,dual glucose-dependent insulinotropic polypeptide(GIP)/GLP-1RA or GLP-1 and glucagon RAs have promoted greater improvement in hepatic steatosis,liver biochemistry,and non-invasive fibrosis tests than monotherapy.Therefore,although to date there are no definitive indications from international drug agencies,there is the hope that soon the therapeutic lines in the most advanced phase of study will be able to provide a therapy for MASLD,one that will certainly include the use of GLP-1RAs as combination therapy.

Glucagon-like peptide-1 receptor agonists as a possible intervention to delay the onset of type 1 diabetes:A new horizon

Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels.However,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells.Recent research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of T1D.GLP-1RAs are medications initially developed for treating type 2 diabetes.They exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric emptying.Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D.This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells.This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.

Is it necessary to stop glucagon-like peptide-1 receptor agonists prior to endoscopic procedure? A retrospective study

BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1 RA)are effective in diabetes and obesity,reducing hyperglycemia by increasing insulin release and delaying gastric emptying.However,they can cause gastroparesis,raising concerns about aspiration during procedures.Recent guidelines advise discontinuing GLP-1 RA before surgery to reduce the risk of pulmonary aspiration.AIM To evaluate the effect of GLP-1 RAs on gastric residual contents during endosco-pic procedures.METHODS A retrospective chart review at BronxCare Health System,New York,from January 2019 to October 2023,assessed gastric residue and aspiration in GLP-1 RA patients undergoing endoscopic procedures.Two groups were compared based on dietary status before the procedure.Data included demographics,symptoms of gastroparesis,opiate use,hemoglobin A1c,GLP-1 agonist indication,endo-scopic details,and aspiration occurrence.IBM SPSS was used for analysis,cal-culating means,standard deviations,and applying Pearson’s chi-square and t-tests for associations,with P<0.05 as being significant.RESULTS During the study,306 patients were included,with 41.2%on a clear liquid/low residue diet and 58.8%on a regular diet before endoscopy.Most patients(63.1%)were male,with a mean age of 60±12 years.The majority(85.6%)were on GLP-1 RAs for diabetes,and 10.1%reported digestive symptoms before endoscopy.Among those on a clear liquid diet,1.5%had residual food at endoscopy compared to 10%on a regular diet,which was statistically significant(P=0.03).Out of 31 patients with digestive symptoms,13%had residual food,all from the regular diet group(P=0.130).No complications were reported during or after the procedures.CONCLUSION The study reflects a significant rise in GLP-1 RA use for diabetes and obesity.A 24-hour liquid diet seems safe for endoscopic procedures without aspiration.Patients with upper gastrointestinal symptoms might have a higher residual food risk,though not statistically significant.Further research is needed to assess risks based on diabetes duration,gastroparesis,and GLP-1 RA dosing,aiming to minimize interruptions in therapy during procedures.

Glucagon-like peptide 1 receptor agonist:A potential game changer for cholangiocarcinoma

Glucagon-like peptide-1 receptor(GLP-1R)agonist,a subgroup of incretin-based anti-diabetic therapies,is an emerging medication with benefits in reducing blood glucose and weight and increasing cardiovascular protection.Contrarily,concerns have been raised about GLP-1R agonists increasing the risk of particular cancers.Recently,several epidemiological studies reported contradictory findings of incretin-based therapy on the risk modification for cholangiocarcinoma(CCA).The first cohort study demonstrated that incretin-based therapy was associated with an increased risk of CCA.Later studies,however,showed a null effect of incretinbased therapy on CCA risk for dipeptidyl peptidase-4 inhibitor nor GLP-1R agonist.Mechanistically,glucagon-like peptide 1 receptor is multifunctional,including promoting cell growth.High GLP-1R expressions were associated with progressive phenotypes of CCA cells in vitro.Unexpectedly,the GLP-1R agonist showed anti-tumor effects on CCA cells in vitro and in vivo with unclear mechanisms.Our recent report also showed that GLP-1R agonists suppressed the expression of GLP-1R in CCA cells in vitro and in vivo,leading to the inhibition of CCA tumor growth.This editorial reviews recent evidence,discusses the potential effects of GLP-1R agonists in CCA patients,and proposes underlying mechanisms that would benefit from further basic and clinical investigation.

Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus

Practical guide:Glucagon-like peptide-1 and dual glucosedependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus common second-line choice after metformin for treating T2DM.Various considerations can make selecting and switching between different GLP-1 RAs challenging.Our study aims to provide a comprehensive guide for the usage of GLP-1 RAs and dual GIP and GLP-1 RAs for the management of T2DM.

Glucagon-like peptide-1 agonists:Role of the gut in hypoglycemia unawareness,and the rationale in type 1 diabetes

Type 1 diabetes is increasing and the majority of patients have poor glycemic control.Although advanced technology and nanoparticle use have greatly enhanced insulin delivery and glucose monitoring,weight gain and hypoglycemia remain major challenges and a constant source of concern for patients with type 1 diabetes.Type 1 diabetes shares some pathophysiology with type 2 diabetes,and an overlap has been reported.The above observation created great interest in glucagon-like peptide-1 receptor agonists(GLP-1)as adjuvants for type 1 diabetes.Previous trials confirmed the positive influence of GLP-1 agonists onβcell function.However,hypoglycemia unawareness and dysregulated glucagon response have been previously reported in patients with recurrent hypoglycemia using GLP-1 agonists.Jin et al found that the source of glucagon dysregulation due to GLP-1 agonists resides in the gut.Plausible explanations could be gut nervous system dysregulation or gut microbiota disruption.This review evaluates the potential of GLP-1 agonists in managing type 1 diabetes,particularly focusing on their impact on glycemic control,weight management,and glucagon dysregulation.We provide a broader insight into the problem of type 1 diabetes mellitus management in the light of recent findings and provide future research directions.

A Retrospective Analysis of Glucagon-Like Peptide 1 Receptor Agonists in Treating Type 2 Diabetes Mellitus Complicated by Nonalcoholic Fatty Liver Disease

Background: The objective of this study was to compare and analyze the variations in clinical indices before and after treatment of type 2 mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) that were treated with glucagon-like peptide 1 receptor agonists (GLP-1RAs). Methods: The electronic medical record system was utilized to search for a total of 16 patients with type 2 diabetes complicated by NAFLD who were hospitalized at the First Affiliated Hospital of Yangtze University from October 2022 to April 2023 and treated with GLP-1RA for the first time. The clinical indices were compared before and after 12 weeks of treatment with GLP-1RA. Results: The liver-spleen CT ratio (L/S), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in all patients treated with GLP-1RA after 12 weeks were significantly different (P 0.05). The patients were categorized into two groups based on the types of GLP-1RAs. The changes in L/S, TC, TG, and LDL-C in the long-acting group after treatment were statistically significant (P Conclusions: GLP-1RAs can improve liver function, regulate lipid metabolism, and reduce the severity of fatty liver in patients with T2DM complicated by NAFLD, which demonstrates the importance of clinical applications.

Glucagon-like peptide-1 receptor agonists:Exploring the mechanisms from glycemic control to treatment of multisystemic diseases

This editorial takes a deeper look at the insights provided by Soresi and Giannitrapani,which examined the therapeutic potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)for metabolic dysfunction-associated fatty liver disease.We provide supplementary insights to their research,highlighting the broader systemic implications of GLP-1RAs,synthesizing the current understanding of their mechanisms and the trajectory of research in this field.GLP-1RAs are revolutionizing the treatment of type 2 diabetes mellitus and beyond.Beyond glycemic control,GLP-1RAs demonstrate cardiovascular and renal protective effects,offering potential in managing diabetic kidney disease alongside renin–angiotensin–aldosterone system inhibitors.Their role in bone metabolism hints at benefits for diabetic osteoporosis,while the neuroprotective properties of GLP-1RAs show promise in Alzheimer's disease treatment by modulating neuronal insulin signaling.Additionally,they improve hormonal and metabolic profiles in polycystic ovary syndrome.This editorial highlights the multifaceted mechanisms of GLP-1RAs,emphasizing the need for ongoing research to fully realize their therapeutic potential across a range of multisystemic diseases.

Glucagon-like peptide 1 receptor activation:anti-inflammatory effects in the brain

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain regions.Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural morphogenesis.The glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous system.After brain insult,microglia are the first cells to respond,followed by reactive astrocytosis.These activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the insult.Furthermore,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many diseases.Several processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control mechanisms.The glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry response.This review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,vascular dementia,or chronic migraine.

Interplay of gut microbiota,glucagon-like peptide receptor agonists,and nutrition:New frontiers in metabolic dysfunction-associated steatotic liver disease therapy

The gut-liver axis plays a crucial role in the development and progression of metabolic dysfunction-associated steatotic liver disease(MASLD).Key metabolites,including lipopolysaccharides,short-chain fatty acids(SCFAs),bile acids,and beneficial gut bacteria such as Bifidobacterium and Lactobacillus,are pivotal in this process.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)show promise in managing MASLD by promoting weight loss,enhancing insulin secretion,and improving liver health.They restore gut-liver axis functionality,and their effects are amplified through dietary modifications and gut microbiometargeted therapies.Emerging research highlights the interplay between GLP-1 RAs and gut microbiota,indicating that the gut microbiome significantly influences therapeutic outcomes.Metabolites produced by gut bacteria,can stimulate glucagon-like peptide-1(GLP-1)secretion,further improving metabolic health.Integrating dietary interventions with GLP-1 RA treatment may enhance liver health by modulating the gut microbiota-SCFAs-GLP-1 pathway.Future research is needed to understand personalized effects,with prebiotics and probiotics offering treatment avenues for MASLD.

Impact of glucagon-like peptide receptor agonists on endoscopy and its preoperative management: Guidelines, challenges, and future directions

Glucagon-like peptide receptor agonists(GLP-1RA)are used to treat type 2 diabetes mellitus and,more recently,have garnered attention for their effect-iveness in promoting weight loss.They have been associated with several gastrointestinal adverse effects,including nausea and vomiting.These side effects are presumed to be due to increased residual gastric contents.Given the potential risk of aspiration and based on limited data,the American Society of Anesthesi-ologists updated the guidelines concerning the preoperative management of patients on GLP-1RA in 2023.They included the duration of mandated cessation of GLP-1RA before sedation and usage of“full stomach”precautions if these medications were not appropriately held before the procedure.This has led to additional challenges,such as extended waiting time,higher costs,and increased risk for patients.In this editorial,we review the current societal guidelines,clinical practice,and future directions regarding the usage of GLP-1RA in patients undergoing an endoscopic procedure.

Effects of glucagon-like peptide-1 receptor agonists on glucose excursion and inflammation in overweight or obese type 2 diabetic patients

BACKGROUND Currently,the lack of comparative studies between weekly and daily formulations of glucagon-like peptide-1 receptor agonists(GLP-1RAs)for glucose excursion is worth investigation.AIM To investigate the effects of weekly and daily formulations of GLP-1RA on glucose excursion and inflammation in overweight and obese patients with type 2 diabetes.METHODS Seventy patients with type 2 diabetes mellitus who were treated at our hospital between January 2019 and January 2022 were enrolled in this retrospective analysis.All patients were treated with metformin.We evaluated changes in blood glucose levels and a series of important indicators in patients before and after treatment with either a weekly or daily preparation of GLP-1RA(group A;n=33 and group B;n=37).RESULTS The degree of decrease in the levels of fasting blood glucose,mean blood glucose,mean amplitude of glycemic excursions,total cholesterol,triglycerides,tumor necrosis factor-α,interleukin-6,and high-sensitivity C-reactive protein after treatment in group A was higher than that in group B(P<0.05),whereas the 2-h postprandial blood glucose levels decreased more so in group B than in group A(P<0.001).However,there were no statistically significant differences in the levels of glycated hemoglobin,standard deviation of blood glucose,coefficient of variation,absolute mean of daily differences,percentage of time with 3.9 mmol/L<glucose<10 mmol/L,and high-and low-density lipoproteins between the two groups(P>0.05).The incidence of adverse reactions was significantly lower in group A than in group B(P<0.05).CONCLUSION The effect of the weekly preparation of GLP-1RA in controlling blood glucose levels in the patients,suppressing inflammation,and reducing adverse reactions was significantly higher than that of the daily preparations,which is worthy of clinical promotion.

Potential therapeutic targets for nonalcoholic fatty liver disease:Glucagon-like peptide 1

Nonalcoholic fatty liver disease(NAFLD)is the most rapidly growing contributor to liver mortality and morbidity.Hepatocellular injury in nonalcoholic steatohepatitis(NASH)is caused by an increase in metabolic substrates(glucose,fructose,and fatty acids),leading fatty acids to participate in pathways that cause cellular injury and a poor response to injury.The pathogenesis of this disease is largely associated with obesity,type 2 diabetes,and increasing age.To date,there are no Food and Drug Administration-approved treatments for NAFLD/NASH or its associated fibrosis.Since one of the pathogenic drivers of NASH is insulin resistance,therapies approved for the treatment of type 2 diabetes are being evaluated in patients with NASH.Currently,the glucagon-like peptide-1 receptor agonist(GLP-1RA)semaglutide is a safe,well-studied therapeutic for NAFLD/NASH patients.Existing research demonstrates that semaglutide can increase the resolution of NASH but not improve fibrosis.However,improving the fibrosis of NAFLD is the only way to improve the long-term prognosis of NAFLD.Given the complex pathophysiology of NASH,combining therapies with complementary mechanisms may be beneficial.Researchers have conducted trials of semaglutide in combination with antifibrotic drugs.However,the results have not fully met expectations,and it cannot be ruled out that the reason is the short trial time.We should continue to pay increasing attention to GLP-1RAs.

Postprandial glucagon-like peptide 1 secretion is associated with urinary albumin excretion in newly diagnosed type 2 diabetes patients

BACKGROUND Microalbuminuria is an early and informative marker of diabetic nephropathy.Our study found that microalbuminuria developed in patients with newly diagnosed type 2 diabetes mellitus(T2DM).AIM To investigate the association between glucagon-like peptide 1(GLP-1)and microalbuminuria in newly diagnosed T2DM patients.METHODS In total,760 patients were recruited for this cross-sectional study.The GLP-1 levels during a standard meal test and urinary albumin-creatinine ratio(UACR)were determined.RESULTS Patients with microalbuminuria exhibited lower GLP-1 levels at 30 min and 120 min during a standard meal test than patients with normal albuminuria(30 min GLP-1,16.7±13.3 pmol vs 19.9±15.6 pmol,P=0.007;120 min GLP-1,16.0±14.1 pmol vs 18.4±13.8 pmol,P=0.037).The corresponding area under the curve for active GLP-1(AUCGLP-1)was also lower in microalbuminuria patients(2257,1585 to 3506 vs 2896,1763 to 4726,pmol×min,P=0.003).Postprandial GLP-1 levels at 30 min and 120 min and AUCGLP-1 were negatively correlated with the UACR(r=0.159,r=0.132,r=0.206,respectively,P<0.001).The prevalence of microalbuminuria in patients with newly diagnosed T2DM was 21.7%,which decreased with increasing quartiles of AUCGLP-1 levels(27.4%,25.3%,18.9%and 15.8%).After logistic regression analysis adjusted for sex,age,hemoglobin A1c,body mass index,systolic blood pressure,estimated glomerular filtration rate,homeostasis model assessment of insulin resistance,AUC_(glucose)and AUC_(glucagon)patients in quartile 4 of the AUCGLP-1 presented a lower risk of microalbuminuria compared with the patients in quartile 1(odds ratio=0.547,95%confidence interval:0.325-0.920,P=0.01).A consistent association was also found between 30 min GLP-1 or 120 min GLP-1 and microalbuminuria.CONCLUSION Postprandial GLP-1 levels were independently associated with microalbuminuria in newly diagnosed Chinese T2DM patients.

Effects of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease and inflammation

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.

Effects of glucagon-like peptide-1 receptor agonists on renal function

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.

Review on the Effect of Glucagon-Like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease（NAFLD） is a common liver disease and it represents the hepatic manifestation of metabolic syndrome, which includes type 2 diabetes mellitus（T2DM）, dyslipidemia, central obesity and hypertension. Glucagon-like peptide-1（GLP-1） analogues and dipeptidyl peptidase-4（DPP-4） inhibitors were widely used to treat T2 DM. These agents improve glycemic control, promote weight loss and improve lipid metabolism. Recent studies have demonstrated that the GLP-1 receptor（GLP-1R） is present and functional in human and rat hepatocytes. In this review, we present data from animal researches and human clinical studies that showed GLP-1 analogues and DPP-4 inhibitors can decrease hepatic triglyceride（TG） content and improve hepatic steatosis, although some effects could be a result of improvements in metabolic parameters. Multiple hepatocyte signal transduction pathways and m RNA from key enzymes in fatty acid metabolism appear to be activated by GLP-1 and its analogues. Thus, the data support the need for more rigorous prospective clinical trials to further investigate the potential of incretin therapies to treat patients with NAFLD.

Is there a role for glucagon-like peptide-1 receptor agonists in the management of diabetic nephropathy?

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.

Glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: An update

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.

Development of therapeutic options on type 2 diabetes in years:Glucagon-like peptide-1 receptor agonist’s role intreatment; from the past to future

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia.Type 2 diabetes (T2DM) accounting for 90% of cases globally.The worldwide prevalence of DM is rising dramatically over the last decades,from 30 million cases in 1985 to 382 million cases in 2013.It’s estimated that 451 million people had diabetes in 2017.As the pathophysiology was understood over the years,treatment options for diabetes increased.Incretin-based therapy is one of them.Glucagon-like peptide-1 receptor agonist (GLP-1 RA) not only significantly lower glucose level with minimal risk of hypoglycemia but also,they have an important advantage in themanagement of cardiovascular risk and obesity.Thus,we will review here GLP-1 RAsrole in the treatment of diabetes.