Metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as non-alcoholic fatty liver disease (NAFLD), is the most prevalent type of chronic liver disease. NAFLD occurs in around 30% of the adult population and is a significant cause of morbidity and mortality from liver disease. More specifically, metabolic dysfunction-associated steatohepatitis (MASH), previously termed non-alcoholic steatohepatitis (NASH), include liver steatosis, liver injury, lobular inflammation, and varying degrees of hepatic fibrosis. MASH accelerates the development of advanced liver fibrosis and cirrhosis, liver cancer, and liver transplantation. In addition, it increases the risk of cardiovascular disease and mortality. The large economic and social burden of MASH and other related diseases has exacerbated with the rising prevalence of obesity, type 2 diabetes mellitus (T2DM), and sedentary lifestyles. Rapidly increasing trends in the prevalence of MASLD and MASH have created a major public health crisis. Estimates demonstrate that more than 350 million people may have MASLD at present. Anticipated increases suggest that this will continue for many years^1-4.

MASH develops because of insulin resistance, excess lipids, reactive oxygen species, mitochondrial dysfunction, persistent inflammation, disrupted gut microbiota, and progressive fibrosis. In the case of insulin resistance, hepatic free fatty acid influx develops. This results in the accumulation of hepatic triglycerides as a consequence of increased lipolysis. This creates a state of lipo-toxicity and inflammation, oxidative stress, and activation of hepatic stellate cells that, ultimately, leads to the development of fibrosis. Therapies focused on multiple metabolic pathways concurrently are more appealing as a result of the complex and inter-related nature of this pathophysiology, in contrast to targeting a single pathway^5-8.

The mainstay of therapy for acute MASH includes lifestyle modification involving diet, physical activity, and intentional weight loss. Patients have difficulty achieving clinically significant weight loss, and there is often poor adherence to weight-loss-sustaining lifestyle interventions. The availability of new anti-obesity medications has improved, but not eliminated, the therapeutic dilemma. The diverse and complex metabolic and inflammatory mechanisms of MASH are not fully treated by any one of these medications. A deeper understanding of the biology of incretin has led to the development of medications that improve glucose homeostasis as well as weight loss and may reduce fat in the liver and inflammation and fibrosis of the liver^9-14.

GLP-1 receptor agonists have demonstrated prominent positive effects on body mass, glucose, and steatosis levels. These beneficial effects are a result of satiety, slowed stomach emptying, enhanced insulin release, reduced glucagon release, and improved insulin sensitivity. However, the traditional GLP-1 receptor agonists only produced mild benefits on hepatic fibrosis. For this reason, the following generations of dual agonists target disparate metabolic pathways. These agents are expected to decrease hepatic steatosis and improve histologic features when used in combination with other pathways¹⁵.

Dual GLP-1/glucagon receptor agonists, like survodutide, combine activations of GLP-1 receptors for anorexia and insulin sensitization and glucagon receptor activation for increased energy expenditure and lipid oxidation and hepatic fat mobilization. GLP-1/GIP co-agonists such as tirzepatide primarily depend on incretin signaling for insulin secretion, insulin sensitization, decreased appetite, and major weight loss. A clinical burden of diabetes is steatotic liver, and both classes of drugs report significant reduction of liver fat and improvements of liver injury biochemical and histological markers in early clinical studies. This puts these two classes of drugs among the best hope for pharmacotherapy of metabolic associated fatty liver disease (MASH)¹⁶.

These findings are promising, but key uncertainties exist when comparing the two mechanistically distinct classes of dual agonists. Several randomized controlled trials have studied drugs in these classes separately. Clinicians cannot currently determine which therapeutic class is likely to improve hepatic steatosis, or liver histology, more. Further, most published systematic reviews have either evaluated incretin therapies as single therapies and benchmarked them against a standard group or conducted an integrated evaluation for incretin therapies and dual GLP-1/glucagon RA against dual GLP-1/GIP co-agonists. Given that studies investigating phase II and phase III clinical trials are likely to be published in the near future, there is an increasing necessity for a focused comparative systematic review¹⁷.

The current systematic review aims to evaluate and compare the dual GLP-1/glucagon receptor agonists and GLP-1/GIP co-agonists for hepatic steatosis in adult MASH patients. The secondary aim is to analyze the impacts of each class of drugs on the resolution of histological MASH, the resolution of fibrosis, reduction of liver function tests, metabolic outcomes, and the drugs’ safety profiles. The intention of this review is to consolidate evidence for clinicians and researchers on these emerging therapeutic strategies and highlight the most pressing research concerns where direct comparative studies are lacking. 

This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 requirements. The goal of the review is to systematically compare the dual glucagon-like peptide-1/glucagon (GLP-1/glucagon) receptor agonists and glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide (GLP-1/GIP) co-agonists to treat hepatic steatosis in adults with metabolic dysfunction-associated steatohepatitis (MASH). The methodology for the review was predefined to reduce bias and increase transparency and reproducibility. Literature Search Strategy A comprehensive literature search was performed in the following electronic databases: • PubMed/MEDLINE • Embase • Scopus • Web of Science Studies were searched from January 2015 to August 2026. There were no restrictions on location. Only studies published in English were considered. Other studies and relevant review articles were searched manually based on references. Free-text and MeSH keywords were combined using Boolean operators (AND/OR). The search strategy included the following terms: ("Metabolic dysfunction-associated steatohepatitis" OR "MASH" OR "Metabolic dysfunction-associated steatotic liver disease" OR "MASLD" OR "Non-alcoholic steatohepatitis" OR "NASH") AND ("GLP-1 receptor agonist" OR "Glucagon-like peptide-1") AND ("Dual agonist" OR "GLP-1/glucagon receptor agonist" OR survodutide OR efinopegdutide OR pemvidutide OR "GLP-1/GIP" OR tirzepatide OR incretin therapy) AND ("hepatic steatosis" OR MRI-PDFF OR fibrosis OR histology) Search strategies were adapted appropriately for each database using their respective indexing terms and search syntax. Eligibility Criteria Inclusion Criteria Only studies that met the following requirements were considered:  Phase II or III randomized controlled trials  Prospective clinical trials  Comparative cohort studies  Participants 18 years of age and older  Patients diagnosed with MASLD or MASH with histological or validated imaging diagnosis  Studies on dual GLP-1/glucagon receptor agonists or GLP-1/GIP co-agonists  Studies describing any predefined efficacy or safety outcomes  Publication in a peer-reviewed journal Exclusion Criteria Studies considered for exclusion:  Animal studies  Case reports and series  Narrative reviews  Systematic reviews and meta-analyses  Editorials and commentaries  Conference abstracts without published data  Pediatric studies  Studies with no accessible outcome data  Duplicate publications and interim analyses of the same study participant Study Selection All citations retrieved during searches were imported into citation management software, and duplicate records were removed. Two reviewers independently assessed the eligibility of titles and abstracts. Full texts of studies deemed potentially eligible were assessed against the predefined inclusion and exclusion criteria. Disagreements between reviewers were resolved through discussion. When a consensus was not achieved, a third reviewer was consulted. The study selection process was documented using a PRISMA 2020 flow diagram. Data Extraction Data extraction was independently performed by two reviewers using a standardized data extraction form. The following variables were collected: • First author • Publication year • Country • Study design • Clinical trial phase • Sample size • Mean participant age • Sex distribution • Baseline body mass index (BMI) • Presence of type 2 diabetes mellitus • Diagnostic criteria for MASH • Duration of follow-up • Histological resolution of MASH • Fibrosis improvement • ALT and AST levels • Weight loss • HbA1c changes • Serious adverse events • Gastrointestinal adverse events • Treatment discontinuation Data Synthesis A qualitative synthesis was undertaken to summarize the attributes and results of all included studies. Clinical heterogeneity was assessed by comparing study design, patient attributes, interventions, treatment durations, and outcome definitions. If sufficiently similar data were identified, it was intended to conduct a quantitative synthesis via meta-analysis. Continuous outcomes were to be described in terms of mean differences (MD) with associated 95% confidence intervals (CIs), and dichotomous outcomes were to be reported in terms of risk ratios (RR) with 95% CIs. Statistical heterogeneity was assessed by the Chi-square test, and was to be quantified by the I² statistic. According to guidelines, I² was to be interpreted as substantial statistical heterogeneity when greater than 50%; in this instance a random-effects model was to be used, and a fixed-effects model would be appropriated otherwise. Risk of Bias Assessment  Bias arising from the randomization process  Bias due to deviations from intended interventions  Bias resulting from missing outcome data  Bias in outcome measurement  Bias in selection of reported results Quality of Evidence The certainty of evidence for each major outcome was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Evidence quality was categorized as high, moderate, low, or very low, considering study limitations, inconsistency, indirectness, imprecision, and publication bias. Ethical Considerations As this study was based exclusively on previously published literature and did not involve direct contact with human participants or access to identifiable patient information, institutional ethical approval and informed consent were not required.

Study Selection

The systematic search of the literature found various studies on incretin-based therapies on MASH and MASHLD. After removing duplicates, the titles and abstracts of the remaining records were assessed. Full-text assessment was done for the ones that met the inclusion and exclusion criteria. The Dual GLP-1 and GLP-1/GIP agonists, as well as the first generation of GLP-1 receptor agonists and the key landmark studies of GLP-1 receptor agonists and hepatic steatosis and histopathology studies, were included. To complement the research, a number of reviews: systematic, meta-analytic, expert, and international clinical practice, were assessed to understand the contemporary situation of therapeutic use of incretin-based agents.

Characteristics of Included Studies

This literature cites evidence from randomized controlled trials (RCTs), Phase II, and Phase III clinial trials, systematic reviews, meta-analyzes, expert reviews, and international clinical practice guidelines published from 2016 to 2026. Clinical studies evaluated liraglutide, semaglutide, cotadutide, efinopegdutide, pemvidutide, tirzepatide, survodutide, mazdutide, efocipegtrutide, and retatrutide in adults with biopsy-proven MASH or imaging-proven MASLD. The majority of randomized studies included obese or overweight participants with type 2 diabetes or metabolic syndrome. The duration of most of these studies was 24 to 72 weeks, and hepatic steatosis was evaluated with MRI-PDFF, liver histology, and liver function tests, as well as staging fibrosis.

Effects on Hepatic Steatosis

Overall, most incremental clinical trials have shown a reduction in liver fat content when using incretin-based therapies. Studies having used MRI-PDFF have shown clinically significant reductions in liver fat content with the use of therapeutic dual agonists, especially survodutide, pemvidutide, efinopegdutide, and tirzepatide. In comparison to the later generation GLP-1 agonists, most of the newer dual agonists induced greater reductions in hepatic steatosis, and more improvements in metabolic parameters, with a greater reduction in body weight.

Of the GLP-1/glucagon receptor agonists, survivodutide showed the greatest reduction in hepatic fat content, with the greatest improvement in several liver function biochemical tests. The same was true for efinopegdutide and pemvidutide, suggesting that the simultaneous glucagon receptor activation is able to enhance hepatic lipid oxidation and decrease intrahepatic fat content. Moreover, GLP-1/GIP co-agonist therapy with tirzepatide showed a significant reduction in hepatic steatosis and improvement of glucose control and significant.

Histological Improvement

Histological improvement was reported in the major biopsy-based randomized controlled trials. The LEAN trial first demonstrated that liraglutide significantly increased the likelihood of non-alcoholic steatohepatitis resolution compared with placebo while reducing progression of fibrosis. Subsequently, semaglutide achieved higher rates of MASH resolution than placebo; however, improvements in fibrosis were less pronounced.

More recent dual agonist studies demonstrated encouraging histological outcomes. The SYNERGY-NASH trial reported significantly higher rates of MASH resolution and greater improvement in liver fibrosis among patients receiving tirzepatide compared with placebo. Similarly, the Phase II trial evaluating survodutide demonstrated substantial histological improvement together with reductions in hepatic steatosis and liver enzyme concentrations, supporting the therapeutic potential of dual GLP-1/glucagon receptor agonism.

Effects on Liver Fibrosis

There has been a noted improvement in hepatic fibrosis in recent clinical trials, though the extent of benefit varied between different therapies. Former GLP-1 receptor agonists mainly ameliorated NASH with little to no reversal of fibrosis. However, improvement in fibrosis in biopsy-proven MASH patients has been documented with both tirzepatide and survodutide, showing that dual agonists may improve fibrosis and NASH more broadly. It is, however, important to note that the extent of improvement in fibrosis, and the improvement of associated liver disease, has yet to be seen because longer studies are needed to be certain that regression of fibrosis is, indeed, permanent.

Liver Biochemistry
Most clinical trials showed that semaglutide, tirzepatide, survodutide, cotadutide, efinopegdutide, and pemvidutide significantly reduced ALT and AST levels. Improved levels of liver enzymes ALT and AST were accompanied by reduced levels of hepatic fat and weight as well as reduced hepatic inflammation. Clinical trials documented consistent improvements in liver enzymes. Improvements in serum liver biochemistries were consistent with reduced hepatic steatosis.

Metabolic Outcomes

Practically, all incretin-based therapies showed beneficial metabolic effects. Almost all studies showed significant reductions in body weight, better control of blood sugar, and increased insulin sensitivity. Given the results, the greatest effect on weight loss of all dual receptor agonists was seen with tirzepatide and survodutide, and it is plausible that adding a second receptor to an agonist may lead to a greater metabolic effect than a GLP-1 receptor agonist. In addition, improvements in HbA1c and blood sugar and other cardiometabolic risk factors were observed in the participants studied with Type 2 diabetes.

Safety and Tolerability

A characteristic of incretin-based therapies is a good safety profile. The adverse events reported in clinical trials were mainly gastrointestinal. Treatment related-adverse events included nausea, vomiting, diarrhea and decreased appetite. The adverse events were generally mild to moderate. Most of the adverse events were observed during dose escalation but persisted as tolerance was established to the therapy. The majority of clinical trials reported that serious adverse events were low, and discontinuation due to adverse events was rarely reported.

Evidence from Systematic Reviews and Clinical Guidelines

Generally, recent systematic reviews and meta-analyses have shown that incretin-based therapies have improved hepatic steatosis, reduced body weight, improved glycemic control, and decreased liver enzyme levels in patients with MASLD and MASH. The most recent international clinical practice guidelines have placed incretin-based therapies at the top of the emerging pharmacological treatments to improve the metabolic dysfunction associated with liver disease in patients with obesity and type 2 diabetes. More specialized reviews have stated that dual GLP-1/glucagon receptor agonists and GLP-1/GIP co-agonists would provide greater benefits to the metabolism and liver than earlier GLP-1 receptor agonists.

Overall Summary of Evidence

Collectively, the available evidence demonstrates that both dual GLP-1/glucagon receptor agonists and GLP-1/GIP co-agonists produce clinically meaningful improvements in hepatic steatosis, liver biochemistry, body weight, and metabolic outcomes among adults with MASH. Histological improvement and fibrosis regression have also been demonstrated in recent placebo-controlled randomized trials, particularly with tirzepatide and survodutide. However, despite these encouraging findings, no direct head-to-head randomized clinical trial has compared the efficacy of these two dual agonist classes. Consequently, current evidence is limited to indirect comparisons across placebo-controlled studies, highlighting an important gap that warrants future comparative clinical trials.

Table 1. Characteristics of Original Clinical Studies Evaluating Incretin-Based Therapies for MASLD/MASH

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; GLP-1, glucagon-like peptide-1; GIP, glucose-dependent insulinotropic polypeptide; MRI-PDFF, magnetic resonance imaging proton density fat fraction; MASLD, metabolic dysfunction-associated steatotic liver disease; MASH, metabolic dysfunction-associated steatohepatitis; RCT, randomized controlled trial.

Table 2. Summary of Systematic Reviews, Meta-Analyses, Clinical Guidelines, and Key Review Articles

Figure 1. Schematic illustration of the mechanisms of action of dual incretin agonists in MASH. The figure compares GLP-1/glucagon receptor agonists and GLP-1/GIP co-agonists, highlighting their complementary metabolic pathways, including enhanced energy expenditure, improved insulin sensitivity, increased hepatic fatty acid oxidation, reduced de novo lipogenesis, and attenuation of hepatic inflammation. The resulting effects include reductions in hepatic steatosis, body weight, metabolic risk factors, and fibrosis, ultimately contributing to histological improvement in MASH. The lower panel summarizes the principal pharmacological differences and clinical outcomes reported for the two therapeutic classes.

Figure 2. Overview of disease progression in MASH and the therapeutic role of dual incretin agonists. The figure illustrates the progression from healthy liver to steatosis, steatohepatitis, fibrosis, and cirrhosis, together with the principal sites of action of GLP-1/glucagon receptor agonists and GLP-1/GIP co-agonists. The lower panels summarize the major clinical outcomes observed in randomized clinical trials, including improvements in hepatic steatosis, histological resolution of MASH, fibrosis, body weight, glycaemic control, and liver enzymes, as well as the overall safety and tolerability profile of these emerging therapies.

This systematic review assesses the existing evidence for the use of dual glucagon-like peptide-1/glucagon (GLP-1/glucagon) receptor agonists and GLP-1/GIP co-agonists for the treatment of steatohepatitis related to metabolic dysfunction (MASH). Improvements in hepatic steatosis, liver function tests, and metabolic parameters, along with reductions in body weight, have been described for both therapeutic classes. There is also evidence for the histological resolution of MASH and regression of liver fibrosis from recently published RCTs. Both classes of drugs were better than placebo in reducing hepatic fat and improving the disease activity, despite different receptor pharmacology. However, the existing evidence is limited to indirect comparisons as no head-to-head randomized clinical trial has directly compared GLP-1/glucagon receptor agonists with GLP-1/GIP co-agonists in MASH, leaving one of the major gaps in current therapeutics11-4. One important observation in this review is the significant decrease in hepatic steatosis with both classes of dual agonists. Excess hepatic triglyceride accumulation is the initial condition for MASH syndrome and contributes to lipotoxicity, oxidative stress, and inflammatory injury of hepatocytes. Therapies lowering liver fat are predicted to prevent the progression from simple steatosis to inflammatory liver injury and fibrosis. Among the studies of MRI-proton density fat fraction, all the dual agonists provided clinically relevant decreases of hepatic fat levels and were accompanied by favorable changes of serum aminotransferases and metabolic risk factors. These data increase the previously published studies with traditional GLP-1 receptor agonists and show that simulation of multiple metabolic pathways may imply greater therapeutic efficacy than GLP-1 receptor activation alone5-7. Among the GLP-1/glucagon receptor agonists, survodutide is the most advanced agent in MASH, and results from the phase II randomized control trial are the most advanced available. In that study, significant improvements in hepatic steatosis and liver enzymes were seen, as was an improvement in histology and a decrease in body weight. Improvement in hepatic steatosis and liver enzymes was postulated to be beyond the improvement expected from weight loss. Mediation analyses from this program suggest that the improvements in the biomarkers of liver inflammation and fibrosis are beyond what is accounted for by weight loss. Thus, glucagon receptor activation may contribute to an anti-inflammatory and antifibrotic effect primarily via improvements in fatty acid oxidation and mitochondrial function, reduced de novo lipogenesis, and increased energy expenditure. GLP-1/glucagon receptor agonists have these distinctive mechanisms of action and may explain the early MASH trial results compared to the more classical GLP-1 receptor agonists8-10. GLP-1/GIP co-agonism has generated a great deal of interest as a potential therapy by the encouraging SYNERGY-NASH trial of tirzepatide. Tirzepatide in that trial had a much greater rate of resolution of MASH and improvement of fibrosis compared to placebo while achieving significant weight loss and better glycaemic control. These results make sense because the receptor of GIP appears to improve the action of GLP-1 in control of hyperglycaemia, enhance pancreatic β-cell function, and has the potential to improve the action of the receptor of GLP-1 in the control of metabolism. The improvement of steatosis and other histological changes in the liver may be caused by the reduction of insulin resistance and the reduction of chronic inflammation of adipose tissue and ectopic lipid deposition. Therefore, the main mechanism of the hepatic action of the GLP-1/GIP co-agonists may be the improvement of the metabolism at the systemic level, while the hepatic action of the GLP-1/glucagon receptor co-agonists may be due to a more direct action on the metabolism of hepatic lipids10-15. An important observation from this review is that the two classes of dual agonist appear to have better therapeutic effects than what has been reported for first-generation GLP-1 receptor agonists. Liraglutide was the first to provide successful pharmacological options for the resolution of steatohepatitis and the slowing of fibrosis progression from the LEAN trial. Later, studies with semaglutide demonstrated even better resolutions of MASH; however,semaglutide, like other selective GLP-1 receptor agonists, did not show significant regression of fibrosis with longer treatment. This is one of the most important limitations of GLP-1 receptor agonism: better resolution of hepatic inflammation is not synonymous with better reversal of established fibrosis. Because of this, the development of dual agonists has focused on steatohepatitis and fibrogenesis16-20. Regression of fibrosis is still the most meaningful therapeutic goal. The stage of fibrosis is the best predictor of liver-related morbidity, hepatocellular carcinoma, liver transplantation, and overall mortality in patients with MASH. Fortunately, recent placebo-controlled trials studying survodutide and tirzepatide have shown the former improving fibrosis with the latter maintaining steatohepatitis. Although regression of fibrosis was shown to be on a different scale in each of the studies, these data suggest that dual agonists may have the ability to decrease the activation of hepatic stellate cells by decreasing inflammatory signaling, oxidative stress, lipotoxicity, and insulin resistance. Fibrosis is a pathologically slowly progressive process and the short duration of the studies (24 - 72 weeks) may not capture the full potential of these therapies. To find out if early histological improvements lead to fibrosis that is permanently decreased, cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver-related mortality, follow-up studies and the ongoing phase III trials are of great importance21-25. This review has found a strong correlation between weight loss and improved outcomes of liver disease. Most of the clinical trials we reviewed showed weight loss. With the dual agonists, weight loss was more pronounced than with the selective GLP-1 receptor agonists. Given that at least a 10% reduction in body weight is associated with the resolution of MASH and improvement of liver fibrosis, we believe the strong obesity effects of tirzepatide and survodutide played a major role in the hepatic effects of these compounds. It has been shown in some of the new studies that loss of weight, particularly with GLP-1/glucagon receptor agonists, does not account fully for the improvement in liver inflammation and fibrosis. Therefore, we believe that the metabolic effects in combination with the direct hepatic effects of new compounds may result in better long-term outcomes in liver disease than the current treatments that mainly focus on weight loss26-30. Current evidence indicates that both GLP-1/glucagon receptor agonists and GLP-1/GIP co-agonists are important novelties in the treatment of MASH. At present, direct evidence is insufficient to support claims of one class of drugs being better than the other, however, based on therapeutic profiles, one class of drugs may be better at some MASH indications than the other. The use of GLP-1/glucagon receptor agonists may be better at enhancing the oxidation of hepatic lipids and decreasing the overall lipid content in the liver. In contrast, the use of GLP-1/GIP co-agonists may be better to treat insulin resistance and lead to greater overall weight loss. Currently, it is not clear if the use of GLP-1/GIP co-agonists may be better than GLP-1/glucagon receptor agonists at leading to a greater reduction in liver fibrosis and improving outcomes related to cirrhosis and liver related cardiovascular outcomes. Future comparative randomized controlled trials should focus on answering these important clinical questions. Limitations: This systematic review has multiple constraints. First, the evidence on dual incretin agonists in MASH is restricted because of the small number of clinical studies. Second, because no direct studies were found to compare GLP-1/glucagon receptor agonists and GLP-1/GIP co-agonists, the comparisons were made based on indirect evidence. Third, the variation in the design of studies, the characteristics of the patients, the duration of treatment and the measures of the outcome may have impacted the findings. Lastly, short follow-up periods of the majority of the studies constrained the evaluation of their long-term efficacy and safety and the regression of fibrosis. Many new large, randomized studies are needed to evaluate the long-term clinical benefits and the comparative effectiveness of these new drugs.

Currently, evidence shows dual GLP-1/glucagon receptor agonists and GLP-1/GIP co-agonists have potential, with great promise as therapeutics for MASH, as both seem to bring improvements for patients regarding hepatic steatosis, liver biochemistry, and body weight and metabolic changes. Recently, some studies recorded some improvements in the histology and in fibrosis with tirzepatide and survodutide. The lack of direct comparative studies, however, does not allow for strong statements for one class of therapeutics over the other. The design of strong, multi-center, head-to-head, and fully randomized controlled trials will later allow for the decision of strong statements related to the comparative benefits and clinical value of these two therapeutic classes.

ACKNOWLEDGMENT:

Grammarly for grammar check, Turnitin for plagiarism, Quilbot for paraphrasing and SPSS version 23.0 for statistical analysis and Chat GPT for critical appraisal.

DECLARATION OF PATIENT’S INTEREST:

Patients’ consent was not required as patients were not physically enrolled in this study.

FINANCIAL SUPPORT AND SPONSORSHIP:

None. The whole project was self-funded by the authors. 

CONFLICTS OF INTEREST:

There are no conflicts of interest.

USE OF ARTIFICIAL INTELLIGENCE (AI)-ASSISTED TECHNOLOGY FOR MANUSCRIPT PREPARATION:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.