Search Results (386)

Background and Aim: Type 2 diabetes (T2D) continues to pose a significant public health challenge worldwide. Among therapeutic options, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have proven effective in optimizing glycemic control and improving cardiometabolic profiles. Semaglutide, now available in an oral formulation, represents a modern strategy to improve patient adherence while supporting glucose and weight regulation. This study primarily investigated the effects of oral semaglutide on key metabolic indicators and secondary endpoints included cardiovascular risk markers (blood pressure and lipid profile) and patient-reported quality of life (QoL). Study Design and Methods: A longitudinal, prospective observational study was conducted involving patients with T2D across two Italian healthcare facilities. Participants were assessed at baseline (T0) and at three subsequent intervals—6 months (T1), 12 months (T2), and 18 months (T3)—following the initiation of oral semaglutide use. Key Findings: Out of 116 participants enrolled, 97 had complete and analyzable data. Across the 18-month follow-up, significant improvements were observed in glycemic parameters, with a notable reduction in HbA1c levels (T0 vs. T3, p = 0.0028; p ≤ 0.05, statistically significant). Self-reported outcomes showed enhanced quality of life, especially in treatment satisfaction and perceived flexibility (T0 vs. T3, p < 0.001). Conclusions: Daily administration of 14 mg oral semaglutide in individuals with T2D resulted in substantial benefits in glycemic regulation, weight reduction, cardiovascular risk management, and overall patient satisfaction. These findings reinforce its potential role as a sustainable and effective option in long-term diabetes care from both a clinical and public health perspective. Full article

The glucagon-like peptide-1 receptor (GLP-1R), which belongs to the class B1 G protein-coupled receptor (GPCR) family, is an important target for treatment of metabolic disorders, including type 2 diabetes and obesity. The growing interest in GLP-1R-based therapies is driven by the development of various functional agonists as well as the huge commercial market. Thus, understanding the structural details of ligand-induced signaling are important for developing improved GLP-1R drugs. Here, we investigated the conformational dynamics of the receptor in complex with a selection of prototypical functional agonists, including CHU-128 (small molecule-biased), danuglipron (small molecule balanced), and Peptide 19 (peptide balanced), which exhibit unique, distinct binding modes and induced helix packing. Furthermore, our all-atom molecular dynamics (MD) simulations revealed atomic feature how different those ligands led to signaling pathway preference. Our findings offer valuable insights into the mechanistic principle of GLP-1R activation, which are helpful for the rational design of next-generation GLP-1R drug molecules. Full article

Background: Chronic Kidney Disease (CKD) is a major global health issue, with diabetes being its primary cause and cardiovascular disease contributing significantly to patient mortality. Recently, two classes of medications—sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—have shown promise in protecting both kidney and heart health beyond their effects on blood sugar control. Methods: We conducted a narrative review summarizing the findings of different clinical trials and mechanistic studies evaluating the effect of SGLT2i and GLP-1 RAs on kidney function, cardiovascular outcomes, and overall disease progression in patients with CKD and DKD. Results: SGLT2i significantly mitigate kidney injury by restoring tubuloglomerular feedback, reducing intraglomerular hypertension, and attenuating inflammation, fibrosis, and oxidative stress. GLP-1 RAs complement these effects by enhancing endothelial function, promoting weight and blood pressure control, and exerting direct anti-inflammatory and anti-fibrotic actions on renal tissues. Landmark trials—CREDENCE, DAPA-CKD, and EMPA-KIDNEY—demonstrate that SGLT2i reduce the risk of kidney failure and renal or cardiovascular death by 25–40% in both diabetic and non-diabetic CKD populations. Likewise, trials such as LEADER, SUSTAIN, and AWARD-7 confirm that GLP-1 RAs slow renal function decline and improve cardiovascular outcomes. Early evidence suggests that using both drugs together may offer even greater benefits through multiple mechanisms. Conclusions: SGLT2i and GLP-1 RAs have redefined the therapeutic landscape of CKD by offering organ-protective benefits that extend beyond glycemic control. Whether used individually or in combination, these agents represent a paradigm shift toward integrated cardiorenal-metabolic care. A deeper understanding of their mechanisms and clinical utility in both diabetic and non-diabetic populations can inform evidence-based strategies to slow disease progression, reduce cardiovascular risk, and improve long-term patient outcomes in CKD. Full article

Obesity is a growing global health concern with widespread impacts on physical, psychological, and social well-being. Clinically, it is a major driver of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and cancer, reducing life expectancy by 5–20 years and imposing a staggering economic burden of USD 2 trillion annually (2.8% of global GDP). Despite its significant health and socioeconomic impact, earlier obesity medications, such as fenfluramine, sibutramine, and orlistat, fell short of expectations due to limited effectiveness, serious side effects including valvular heart disease and gastrointestinal issues, and high rates of treatment discontinuation. The advent of glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, tirzepatide) has revolutionized obesity management. These agents demonstrate unprecedented efficacy, achieving 15–25% mean weight loss in clinical trials, alongside reducing major adverse cardiovascular events by 20% and T2D incidence by 72%. Emerging therapies, including oral GLP-1 agonists and triple-receptor agonists (e.g., retatrutide), promise enhanced tolerability and muscle preservation, potentially bridging the efficacy gap with bariatric surgery. However, challenges persist. High costs, supply shortages, and unequal access pose significant barriers to the widespread implementation of obesity treatment, particularly in low-resource settings. Gastrointestinal side effects and long-term safety concerns require close monitoring, while weight regain after medication discontinuation emphasizes the need for ongoing adherence and lifestyle support. This review highlights the transformative potential of incretin-based therapies while advocating for policy reforms to address cost barriers, equitable access, and preventive strategies. Future research must prioritize long-term cardiovascular outcome trials and mitigate emerging risks, such as sarcopenia and joint degeneration. A multidisciplinary approach combining pharmacotherapy, behavioral interventions, and systemic policy changes is critical to curbing the obesity epidemic and its downstream consequences. Full article

Background and Objectives: Type 2 diabetes (T2D) is a global health burden with increasing prevalence, necessitating effective management strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as beneficial therapies, promoting both glycemic control and weight loss, yet real-world data on sex differences in response are limited. This study aimed to investigate sex-based differences in glycemic and weight outcomes, as well as adverse effects, in T2D patients treated with GLP-1 RAs at a single diabetes center. Materials and Methods: In this retrospective analysis, 114 patients (58.8% men) with T2D who were initiated on GLP-1 RA therapy between 2015 and 2023 were evaluated. Data on HbA1c, BMI, and adverse events were collected at baseline and 3, 6, and 12 months post-treatment initiation. Results: Our findings indicated a statistically significant HbA1c reduction (from 8.6% at GLP-1 RA initiation to 6.9% at 12 months in men (p < 0.001) and from 8.4% at initiation to 7.0% at 12 months after GLP-1 RA initiation (p < 0.001) in women). By 12 months, a significantly greater proportion of women compared to men achieved ≥ 5% (51.1% vs. 28.4%, p = 0.019) and ≥10% weight loss (29.8% vs. 9.0%, p = 0.006), with both differences reaching statistical significance. A statistically significant difference in weight loss in mean weight change and percent weight change in men vs. women was observed from month 6 of therapy. Conclusions: These findings underscore the effectiveness of GLP-1 RAs in improving glycemic control and weight loss in a real-world setting and suggest that women may experience greater weight reduction. Understanding these differences could inform personalized treatment strategies for optimized outcomes in T2D management. Full article

Background: Semaglutide and Liraglutide are medications in the Glucagon-like peptide-1 agonists (GLP-1 RAs) class used to manage type 2 diabetes mellitus and obesity in Saudi Arabia. Although the 1.0 mg once weekly dosage of Semaglutide does not have a labeled indication for the management of obesity, many believe that this dosage is more effective than the 3.0 mg once daily Liraglutide dosage for the management of both diabetes and obesity. Objective: To compare the effectiveness of the dosage of 1.0 mg of Semaglutide administered once weekly versus 3.0 mg of Liraglutide administered once daily in controlling HbA1c levels, promoting weight loss, and evaluating their financial implications among obese patients in Saudi Arabia using real-world data. Methods: A retrospective review of Electronic Medical Records (EMRs) from January 2021 to June 2024 was conducted on patients prescribed Semaglutide or Liraglutide for at least 12 months. Exclusion criteria included pre-existing severe conditions (e.g., cardiovascular disease, stroke, or cancer) and missing baseline data. The primary outcomes assessed were changes in HbA1c, weight, and direct medical costs. Results: Two hundred patients (100 patients on the 1.0 mg once weekly dose of Semaglutide and 100 patients on the 3.0 mg once daily dose of Liraglutide) of those randomly selected from the EMRs met the inclusion criteria and were included in the analysis. Of the 200 eligible patients (65.5% female, mean age 48.54 years), weight loss was greater with Semaglutide (−8.09 kg) than Liraglutide (−5.884 kg). HbA1c reduction was also greater with Semaglutide (−1.073%) than Liraglutide (−0.298%). The use of Semaglutide resulted in lower costs of USD −1264.76 (95% CI: −1826.82 to 33.76) and greater reductions in weight of −2.22 KG (95% CI: −7.68 to −2.784), as well as lower costs of USD −1264.76 (95% CI: (−2368.16 to −239.686) and greater reductions in HbA1c of −0.77% (95% CI: −0.923 to −0.0971) in more than 95% of the cost effectiveness bootstrap distributions. Conclusions: Semaglutide 1.0 mg weekly seems to be more effective and cost-saving in managing prediabetes, diabetes, and obesity compared to Liraglutide 3.0 mg daily. Future studies should examine these findings using a more representative sample and a robust study design. Full article

Background/Objectives: Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is a well-established pharmacologic agent for inducing weight loss in individuals with obesity and is prescribed regardless of type 2 diabetes mellitus (DM) status. However, it remains unclear whether the weight-lowering efficacy of semaglutide differs significantly between individuals with and without DM. To address this question, we conducted a systematic review and meta-analysis comparing the effects of once-weekly subcutaneous semaglutide at 2.4 mg on weight loss in adults with and without DM. Methods: A comprehensive literature search was performed using the PubMed database to identify randomized controlled trials (RCTs) involving overweight or obese adults receiving semaglutide at 2.4 mg weekly for 40 to 70 weeks. Using a random-effects model, we estimated the weighted mean differences in body weight reduction between the two groups. Nine RCTs met the inclusion criteria, among which two provided subgroup data for participants with and without DM within the same trial population. Registration number in PROSPERO: CRD420251077610. Results: In participants with DM (n = 4 studies), semaglutide was associated with a weighted mean body weight reduction of −6.34% (95% confidence interval: −6.98 to −5.69), with negligible heterogeneity across studies (I² = 0.0%). By contrast, among participants without DM (n = 7 studies), the weighted estimate of weight loss was −11.57% (95% confidence interval: −12.94 to −10.19), with moderate heterogeneity observed (I² = 63.6%). Conclusions: The observed difference in weight loss efficacy between the groups was clinically meaningful. While once-weekly semaglutide at 2.4 mg elicited significant weight loss in both populations, the magnitude of effect was notably greater in those without DM. This disparity may be explained by metabolic characteristics frequently present in individuals with DM, such as insulin resistance, hyperinsulinemia, and compensatory mechanisms related to glycemic control. Full article

Diabetes mellitus and atrial fibrillation (AF) frequently coexist, creating a complex bidirectional relationship that exacerbates cardiovascular risk and challenges clinical management. Diabetes fosters a profibrotic, pro-inflammatory, and proarrhythmic atrial substrate through a constellation of pathophysiologic mechanisms, including metabolic remodeling, oxidative stress, mitochondrial dysfunction, ion channel dysregulation, and autonomic imbalance, thereby promoting AF initiation and progression. Conventional rhythm control strategies remain less effective in diabetic individuals, underscoring the need for innovative, substrate-targeted interventions. In this context, sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as promising agents with pleiotropic antiarrhythmic properties, modulating fibrosis, inflammation, and mitochondrial integrity. Moreover, advances in anti-inflammatory, antifibrotic, and ion channel-modulating therapeutics, coupled with novel mitochondrial-targeted strategies, are reshaping the therapeutic landscape. Multi-omics approaches are further refining our understanding of diabetes-associated AF, facilitating precision medicine and biomarker-guided interventions. This review delineates the molecular nexus linking diabetes and AF, critically appraises emerging rhythm control strategies, and outlines translational avenues poised to advance individualized management in this high-risk population. Full article

Cardiovascular diseases (CVDs) are the leading cause of global mortality, with type 2 diabetes mellitus (T2DM) and obesity significantly increasing the risk of CVD. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4is) have gained attention for their potential cardioprotective effects. Therefore, this review aims to explore the molecular mechanisms underlying the cardiovascular benefits of these agents. A literature review was conducted searching PubMed databases from 1990 to January 2025, including research on the effects of GLP-1 RA and DPP-4i on cardiovascular health, specifically concerning atherosclerosis, coronary artery disease, vascular health, cardiac arrhythmias, myocardial infarction (MI), and heart failure, with a focus on the biochemical and molecular effects of these drugs. We analyzed 131 scientific publications, which indicate that GLP-1 RA and DPP-4i significantly reduce cardiovascular risk and major adverse cardiovascular events (MACEs), including atherosclerosis, myocardial infarction, and cardiac arrhythmias. These clinical outcomes are attributed to the mitigation of oxidative stress, inflammation, and endothelial dysfunction as well as improvement in mitochondrial function and lipid metabolism. GLP-1 RAs offer substantial cardiovascular benefits, making them valuable in managing T2DM and reducing CVD risk. Their integration into treatment regimens for CVD can reduce hospitalization rates, improve quality of life, and extend life expectancy. DPP-4is, while beneficial, are less effective in cardiovascular protection. Further research is needed to optimize therapeutic strategies and broaden the clinical application of these agents in cardiometabolic care. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is frequently associated with depressive disorder (DD), which negatively impacts glycemic control and overall metabolic outcomes. Recent evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may exert neuroprotective effects and modulate mood. Likewise, it is unknown whether the presence of a DD, due to increased brain inflammation, could lead to a poorer response to GLP-1 RAs in terms of weight loss. This study evaluates the impact of DD on metabolic outcomes in individuals treated with GLP-1 RAs. Methods: We conducted a retrospective longitudinal study including 115 patients with T2DM treated with GLP-1 RAs for at least six months. DD was identified based on a documented clinical diagnosis, chronic antidepressant use, or a Beck Depression Inventory (BDI) score ≥16. Metabolic parameters, including glycated hemoglobin (HbA1c), fasting glucose, the body mass index (BMI), the waist circumference, and triglycerides, were compared between patients with and without DD. Results: Patients with DD had significantly higher baseline HbA1c (7.5% vs. 6.9%, p = 0.01), fasting glucose, and triglyceride levels. The waist circumference was also higher in the DD group (p = 0.001). However, no significant differences were observed in weight loss or BMI reductions following the GLP-1 RA treatment. Final HbA1c levels remained higher in the DD group (7.2% vs. 7.0%, p = 0.01). Conclusions: While DD is associated with a poorer baseline metabolic control in T2DM, it does not appear to impair the weight loss efficacy with GLP-1 RAs. However, patients with DD maintain higher post-treatment HbA1c levels, underscoring the need for integrated metabolic and psychiatric care in diabetes management. Full article

Obesity is considered a global pandemic. In Mexico, 7/10 adults, 4/10 adolescents, and 1/3 children are overweight or obese, and it is estimated that 90% of cases of type 2 diabetes (T2D) are attributable to these pathologies. Visceral adipose tissue (VAT) presents increased lipolysis, lower insulin sensitivity, and greater metabolic alterations. Glucagon-like peptide-1 (GLP-1) is a polypeptide incretin hormone that stimulates insulin secretion dependent on the amount of oral glucose consumed, reduces plasma glucagon concentrations, slows gastric emptying, suppresses appetite, improves insulin synthesis and secretion, and increases the sensitivity of β cells to glucose. Liraglutide is a synthetic GLP-1 analog that reduces VAT and improves the expression of Glucose transporter receptor type 4 (GLUT 4R), Mitogen-activated protein (MAP kinases), decreases Fibroblast growth factor type β (TGF-β), reactivates the peroxisome proliferator-activated receptor type ɣ (PPAR-ɣ) pathway, and decreases chronic inflammation. Currently, there are many studies that explain the decrease in VAT with these medications, but there are no studies that compare the decrease in patients with obesity and prediabetes vs. obesity and type 2 diabetes to know which population obtains a greater benefit from treatment with this pharmacological group; this is the reason for this study. The primary objective was to compare the difference in the determination of visceral adipose tissue in people with obesity and type 2 diabetes vs. obesity and prediabetes treated with liraglutide. Methods: A quasi-experimental, analytical, prolective, non-randomized, non-blinded study was conducted over a period of 6 months in a tertiary care center. A total of 36 participants were divided into two arms; group 1 (G1: Obesity and prediabetes) and group 2 (G2: Obesity and type 2 diabetes) for 6 months. Inclusion criteria: men and women ≥18 years with type 2 diabetes, prediabetes, and obesity. Exclusion criteria: Glomerular filtration rate (GFR) < 60 mL/min/1.73 m² elevated transaminases (>5 times the upper limit of normal), and use of non-weight-modifying antidiabetic agents. Conclusions: No statistically significant difference was found in the decrease in visceral adipose tissue when comparing G1 (OB and PD) with G2 (OB and T2D). When comparing intragroup in G2 (OB and T2D), greater weight loss was found [(−3.78 kg; p = 0.012) vs. (−3.78 kg; p = 0.012)], as well differences in waist circumference [(−3.9 cm; p = 0.049) vs. (−3.09 cm; p = 0.017)], and glucose levels [(−1.75 mmol/L; p = 0.002) vs. (−0.56 mmol/L; p = 0.002)], A1c% [(−1.15%; p = 0.001) vs. (−0.5%; p = 0.000)]. Full article

Gout, a metabolic and autoinflammatory disease, is the most common form of inflammatory arthritis worldwide. Hyperuricemia may result in monosodium urate (MSU) crystals forming and depositing in joints and surrounding tissues, triggering an autoinflammatory response. Effective urate-lowering therapies, as well as anti-inflammatory medications, are used to treat gout. Over the past few decades, new antihyperglycemic drug classes with different modes of action have been added to treat hyperglycemia in type 2 diabetes mellitus (T2DM). Two of these drug classes, sodium–glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), have reduced cardiovascular and renal events and mortality. Several clinical studies have demonstrated that SGLT2 inhibitors possess urate-lowering properties, which may be beneficial for treating gout patients, particularly those with comorbid T2DM. Regarding SGLT2 inhibitors, some researchers have suggested that their benefits are partly explained by their ability to reduce serum urate (SU) levels, probably through increased urinary uric acid excretion. The effect of GLP-1 RA on SU levels and urinary excretion of uric acid in humans is unclear. This paper reviews the mechanisms of action of SGLT2 inhibitors and GLP-1RA, both approved and in development. Additionally, it examines what is known about their structure–activity relationships, uricosuric effects, pharmacokinetic profiles, and adverse effects. Full article

Glucagon-like peptide-1 (GLP-1) has emerged as a pivotal regulator in the management of glucose homeostasis, glycogen metabolism, and energy balance, positioning it as a critical therapeutic target for addressing obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). GLP-1 receptor agonists (GLP-1RAs) have shown promise for improving glycemic control and reducing weight through appetite regulation, delayed gastric emptying, and energy expenditure modulation. This narrative review explores the mechanisms of GLP-1-mediated glycogen metabolism and energy expenditure, particularly in key tissues—pancreas, liver, skeletal muscle, and adipose tissue. In the pancreas, GLP-1 enhances insulin secretion and beta-cell function. In the liver, it promotes glycogen synthesis via insulin-dependent and potential insulin-independent pathways, involving protein kinase B (AKT) and AMP-activated protein kinase (AMPK) signaling. Skeletal muscle benefits from GLP-1 through increased glucose uptake, AMPK activation, and mitochondrial function, facilitating glycogen storage. In adipose tissue, GLP-1 stimulates brown adipose tissue (BAT) thermogenesis and energy expenditure, contributing to weight loss. This increase in energy expenditure, along with enhanced glycogen metabolism, is a plausible mechanism for the weight loss observed with GLP-1RAs. Despite these advances, significant knowledge gaps remain, particularly regarding the direct hepatic effects of GLP-1, the extent to which it modulates glycogen metabolism in vivo, and its impact on thermogenesis in humans. Future research focusing on both the tissue-specific actions of GLP-1 and its systemic role in energy homeostasis and metabolic regulation will be essential for optimizing its therapeutic potential. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), which were originally developed for managing type 2 diabetes by enhancing insulin secretion and reducing appetite, have emerged as promising candidates in alcohol use disorder (AUD). These medications offer a dual mechanism of action that aligns with the multifaceted nature of addiction by targeting both peripheral metabolic and central reward pathways. This review focused on the current clinical trials and real-world evidence regarding the effects of GLP-1RAs as novel therapeutics for AUD. We also discussed early but encouraging results from clinical trials in AUD, observational and real-world evidence, safety profiles, psychiatric considerations, and future directions leading beyond GLP-1RAs. Methods: A comprehensive English-language literature search was conducted per PRISMA guidelines across PubMed, Medline, Google Scholar, Web of Science, and trial registries. Using targeted keywords, we identified relevant clinical and observational studies on GLP-1RAs for alcohol use disorder, excluding off-topic or non-English works and assessing all studies for eligibility. Results: Out of 1080 records identified, seven studies met the inclusion criteria. The findings from recent clinical trials, large-scale observational studies, and real-world evidence suggest that GLP-1RAs may significantly reduce alcohol consumption, cravings, and alcohol-related hospitalizations. Their central effect on reward processing, coupled with a generally favorable safety profile, supports their potential therapeutic role beyond metabolic disorders. Conclusions: Emerging evidence positions GLP-1RAs as a promising new pharmacologic approach for managing AUD. Ongoing and future research should prioritize larger, longer-duration randomized controlled trials that include diverse populations, with specific attention to treatment motivation, co-occurring psychiatric conditions, and long-term outcomes. Full article

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly encompassed under nonalcoholic fatty liver disease (NAFLD), is a growing global health burden associated with progression to cirrhosis and hepatocellular carcinoma. Resmetirom, a thyroid hormone receptor-β (THR-β) agonist, and semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), have emerged as promising agents targeting distinct metabolic and inflammatory pathways. This systematic review compares the safety and efficacy of resmetirom and semaglutide in MASLD. Methods: We conducted a comprehensive search of PubMed, Embase, and Google Scholar for randomized controlled trials and clinical studies published between January 2014 and April 2025, following PRISMA guidelines. Studies assessing the efficacy and safety of resmetirom and/or semaglutide in MASLD or NASH were included. Data extraction was performed by two independent reviewers, and a narrative synthesis was undertaken due to the heterogeneity in study design and outcome measures. Results: Fourteen studies encompassing over 4500 patients were analyzed. Resmetirom demonstrated consistent reductions in hepatic fat (≥30% in >50% of patients) and improvements in fibrosis (≥1 stage in up to 26.4% of patients), as evidenced in the MAESTRO-NASH trial. Semaglutide achieved higher rates of NASH resolution (up to 62.9%) without worsening fibrosis, especially among patients with type 2 diabetes or obesity, although fibrosis improvement was less consistently observed. Resmetirom was well tolerated with low discontinuation rates, while semaglutide was associated with more frequent, yet manageable, gastrointestinal adverse events. Conclusions: Both resmetirom and semaglutide show therapeutic potential for MASLD. Resmetirom offers more consistent antifibrotic effects, while semaglutide excels in NASH resolution and metabolic improvement. The absence of direct comparative trials underscores the need for future head-to-head studies to guide tailored treatment strategies in MASLD management. Full article