Liraglutide

Novel Amylin-Based Therapies for Weight Management in Adults With Overweight or Obesity Without Diabetes: A Network Meta-Analysis.

A B M Kamrul-Hasan, Ibrahim Khalil, Kunal Mahajan +3 more

Long-acting amylin-based therapies (ABTs) are emerging anti-obesity agents; we sought to compare their effects on weight and anthropometric outcomes in adults with overweight/obesity without diabetes, evaluate gastrointestinal (GI) safety, and rank agents and doses within a network meta-analysis (NMA) framework.

A single centre retrospective study of the long‑term weight and pregnancy-related outcomes in women of reproductive age before and after liraglutide exposure.

Tariq Chukir, Hubaib Haider, Shaunak Sarkar +4 more

The impact of GLP‑1 receptor agonist exposure prior to pregnancy on pregnancy-related outcomes remains unclear, with studies reporting mixed findings.

The glucagon-like peptide-1 receptor agonist, Ex4, reduces intromission in sexually experienced male mice.

Olesya Shevchouk, Christian E Edvardsson, Mia Ericson +2 more

The physiological effects of glucagon-like peptide-1 (GLP-1) are vast, including food and glucose homeostasis. As the half-life is short, both short-acting, exendin-4 (Ex4) and long-acting, liraglutide and dulaglutide, GLP-1 receptor (GLP-1R) agonists have been developed and are approved for type 2 diabetes and/or obesity. They have also been found to reduce behaviors linked to addictive drugs through involvement of mesolimbic brain regions such as the medial amygdala. Additionally, Ex4 reduces sexual interactions in sexually naïve male mice and experienced females. However, the effects of GLP-1, short- and long-acting GLP-1R agonists on sexual behaviors in sexually experienced males remain unknown. Therefore, we examined how GLP-1 and Ex4 affect sexual behavior in experienced male mice, influenced associated neurochemical changes in the medial amygdala, and evaluated the potential modulatory factors through social behaviors. Additionally, we assess whether long-acting GLP-1R agonists impacted similar behaviors as well as the levels of corticosterone and insulin. Ex4 reducced the number of intromissions and ejaculations in sexually experienced male mice without GLP-1 having an effect. Moreover, social behaviors were unaffected by short-acting GLP-1R agonists. In the medial amygdala of these male mice treated with Ex4, the levels of glutamate and other amino acids were lower. Conversely, liraglutide and dulaglutide did not modify sexual behaviors but enhanced time in the social zone, with no effect on corticosterone or insulin levels. Together, these studies suggest that GLP-1R activation modulates both sexual and social behaviors, but the outcome depends on which agonists have been used.

Incidence of Barrett's esophagus and esophageal cancer following sleeve gastrectomy versus liraglutide therapy.

Edward Butt, Juliana Yang

Sleeve gastrectomy has consistently been linked to gastroesophageal reflux disease and Barrett's esophagus. At the same time, the long-term effects of glucagon-like peptide-1 receptor agonists, particularly short-acting agents such as liraglutide, are less well understood. We compared the incidence of Barrett's esophagus and esophageal cancer among patients treated with liraglutide vs. those who underwent sleeve gastrectomy.

The Liraglutide Effects in Atrial Fibrillation (LEAF) Study.

Jeffrey J Goldberger, Raul D Mitrani, Joel Fishman +11 more

Atrial fibrillation (AF) ablation continues to offer mediocre outcomes, particularly for persistent AF. Obesity and epicardial adipose tissue (EAT) are associated with AF and ablation outcomes. Risk factor modification (RFM), including weight loss, improves AF treatment outcomes. Liraglutide, a glucagon-like peptide-1 receptor agonist, leads to weight loss and EAT reduction.

In Vitro Characterization of Agonist and Antagonist Peptide Binding Interaction Kinetics to GLP-1R in HEK293T Cells Using Surface Plasmon Resonance Microscopy.

Miyuki A Thirumurthy, Jesús S Aguilar Díaz de León, Shuchong Pan +1 more

The glucagon peptide 1 receptor (GLP-1R), a class-B-type G protein-coupled receptor (GPCR), is a key therapeutic target for many metabolic disorders, including obesity and type 2 diabetes, due to its central role in glucose homeostasis and insulin secretion. Despite its pharmacological importance, studying the binding kinetics of its multidomain engagement with peptide ligands remains a challenge using purified receptor systems. The isolated forms fail to capture the dynamic behavior of membrane-bound GPCRs in a physiologically relevant context. A deeper understanding of the interaction kinetics of agonist and antagonist binding to GLP-1R domains is essential for rational drug design, as the activation of the receptor depends on distinct binding modes that modulate downstream signaling efficacy. Here we employ surface plasmon resonance microscopy (SPRM) on HEK293T cells overexpressing GLP-1R to visualize and quantify the label-free kinetic interactions of ligands on whole single cells in real time. Using three different agonists (GLP-1, liraglutide, exendin-4) and one antagonist (exendin-9), we demonstrate that the agonists exhibit a two-mode/bivalent binding behavior with C-terminal engagement of the extracellular domain (ECD) and N-terminal engagement of the transmembrane domain (TMD). In contrast, the antagonist exendin-9 binds with a single mode, exclusively to the ECD. Importantly, SPRM resolves not only the presence of dual-domain engagement but also the stability and heterogeneity of these interactions, enabling discrimination between full and partial agonism. Notably, liraglutide displays the highest interaction affinity and the greatest amount of activation through TMD binding, which agrees with its known structural optimization and superior therapeutic performance. This study highlights SPRM as a powerful, label-free platform for probing the on-cell binding kinetics of GPCR interactions with peptides, providing quantitative insights into the activation efficiency of agonists and selectivity of antagonists in ways conventional receptor assays cannot.

Effects of Agonists on Skin Quality: A Comprehensive Literature Review.

Mauro Barone, Beniamino Brunetti, Roberta D'Emilio +3 more

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), particularly semaglutide and liraglutide, have revolutionized the treatment of type 2 diabetes and obesity due to their potent effects on weight loss and glycemic control. However, emerging evidence has highlighted dermatologic side effects associated with the rapid reduction of subcutaneous adipose tissue, particularly in the context of aesthetic skin integrity. This systematic review aims to comprehensively evaluate the current evidence on the effects of GLP-1 RAs on skin quality, including dermal structure alterations, adipose compartment loss, and skin elasticity changes.

The GLP-1 Receptor Agonist Liraglutide Promotes Anticancer Activities in MCF7 Breast and PC-3 Prostate Cancer Cells by Modulating Glycolysis, Oxidative Stress and Adipokines.

Bassem Refaat, Mohamed E Elzubier, Akhmed Aslam +2 more

This research explored the anticancer activities of the glucagon-like peptide-1 receptor agonist (GLP1Ra) liraglutide using MCF7 breast and PC-3 prostate cancer cell lines. The study focused on key molecular pathways related to glycolysis and oxidative stress alongside adipokine profiles. The expression of GLP1R and its downstream signalling components (cAMP and PKA) was quantified in untreated and treated cells. Alterations in cell cycle and cell apoptosis were evaluated by a flow cytometer. Expression of oncogenic (CCND1, CCND3, BCL2, survivin) and tumour suppressor (p21, p27, BAX, Caspase-3) proteins, the PI3KAkt/mTOR axis and glycolytic regulators (HIF-α, LDHA, PDHK1, PDH) was examined by Western blot analysis. Adipokine concentrations (adiponectin, leptin, resistin), pro-oxidants (ROS/RNS, MDA, protein carbonyls) and antioxidants (GSH, CAT) were assessed using ELISA. Liraglutide treatment led to pronounced upregulation of GLP1R expression and activation of cAMP/PKA signalling in both cancer cell lines. Antiproliferative effects were evident through induced apoptosis and cell cycle arrest alongside inhibition of CCND1, CCND3, BCL2 and survivin with increased p21, p27, BAX and Caspase-3 expression. The PI3K/Akt/mTOR pathway was suppressed, while its negative regulators, PTEN and AMPKα, were upregulated. Liraglutide also shifted metabolic activity towards oxidative phosphorylation by suppressing HIF-α, LDHA and PDHK1, whereas PDH levels increased. Additionally, liraglutide raised adiponectin levels while reducing leptin and resistin. Oxidative stress markers increased substantially, accompanied by a decrease in antioxidant levels in both cell lines. Liraglutide induced anticancer effects in breast and prostate cancer cells, possibly by promoting oxidative phosphorylation, modulating adipokines and inducing oxidative stress-mediated apoptosis.

GLP-1 receptor agonists and surgical care: implications for bariatric Procedures, perioperative Outcomes, and nutritional optimization.

Zeyad Elawa, Ahmed Khalil, Ahmed Kardousha +2 more

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for obesity and type 2 diabetes and are now frequently encountered in patients undergoing bariatric and other elective surgeries. Their effects on gastric motility, appetite, and nutrient intake have important implications for perioperative safety, surgical outcomes, and nutritional care.

GLP-1 Agonists in Orthopedic Surgery: A Narrative Review of Bone Health and Surgical Implications.

Mateo Restrepo Mejia, Justin Tiao, Alexander Yu +4 more

Glucagon-like peptide-1 (GLP-1) receptor agonists, commonly used for glycemic control in patients with type 2 diabetes and for weight loss in obese patients, have been increasingly used due to their effectiveness in treating these conditions and in reducing cardiovascular events. Yet evidence is limited surrounding their impact on bone health and on patients undergoing orthopedic procedures. This narrative review explores the mechanisms of action of GLP-1 agonists, their effects on bone health, and the implications of their use in perioperative patents undergoing orthopedic surgery, with an emphasis on spine surgery. Basic science studies suggest that GLP-1 agonists may enhance bone mineral density and reduce bone resorption through various molecular pathways; clinical studies of their impact on fracture risk and bone health show mixed results. Also, the perioperative use of GLP-1 agonists poses challenges due to their effects on gastric motility and potential medication interactions. Nonetheless, achieving proper glycemic control with GLP-1 agonists may benefit patients with diabetes or obesity undergoing orthopedic procedures, particularly in preoperative weight management and glycemic control. Further research is needed to clarify their long-term effects on bone health and their perioperative use in orthopedic patients.

GLP-1 agonist liraglutide decreases operant methamphetamine intake in rats under conditions of short- but not extended-access to the drug.

Maria Hrickova, Sefa Furkan Demirci, Petra Amchova +1 more

Glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as a therapeutic strategy for reducing drug craving and intake. However, their efficacy in methamphetamine use disorder remains unexplored. This study assessed the effects of repeated liraglutide treatment on methamphetamine intravenous self-administration in rats.

Liraglutide and Recurrent Stroke by Baseline Insulin Resistance: A Post Hoc Analysis of the LAMP Trial.

Longyan Lu, Bing Yang, Yao Wang +10 more

Glucagon-like peptide-1 receptor agonists reduce major adverse cardiovascular events in type 2 diabetes. Although body mass index does not seem to modify these effects, whether insulin resistance influences treatment efficacy remains unclear.

Association Between Glucagon-Like Peptide-1 Receptor Agonists and Suicidality: A Systematic Review.

Timothy H Chan, Leon E Cosler, Michael R Gionfriddo +3 more

We aimed to examine the association between GLP-1 RA use and suicidal ideation or behaviours through a systematic review of observational studies.

Switching patterns of GLP-1 receptor agonists from 2018 to 2025 in the largest private healthcare network in Poland.

Krzysztof Łupina, Artur Dziewierz, Jakub Janczura +1 more

To characterize switching among GLP-1 receptor agonists (GLP-1 RAs) in a large private-sector cohort in Poland and to quantify therapy- and patient-level associations with switching while accounting for switching opportunity and calendar-time dynamics.

Six-month effects of liraglutide and dapagliflozin on lipid profile, cardiovascular risk, and NT-proBNP levels in patients with metabolic dysfunction-associated steatotic liver disease.

Volodymyr Cherniavskyi, Artem Akimov, Luiza Parunian +2 more

Aim: This study assessed and compared changes in lipid profile and cardiovascular risk in patients with metabolic dysfunction-associated steatotic liver disease after six months of liraglutide or dapagliflozin treatment. We also evaluated changes in N-terminal pro-B-type natriuretic peptide levels.

Liraglutide Causing Pancreatitis in an Indian Obese Female: A Case Report and Review of the Literature.

Jitendra Singh, Anju Dinkar, Rajeev Verma +3 more

Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is commonly prescribed for obesity and type 2 diabetes mellitus (T2DM). While its metabolic benefits are well-established, rare cases of acute pancreatitis (AP) have raised concerns about drug safety. Despite regulatory warnings from the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), causality remains debated due to confounding factors and limited human data.

Glucagon-Like Peptide-1 Receptor Agonists Inhibit the Initiation of Toxic Amyloid-β42 Aggregation.

Lucas B Fallot, Carol A Anderson, Johnathan R Pinc +10 more

The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is important in Alzheimer's disease (AD). Preclinical and clinical findings support that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can protect against neuroinflammation and neurodegeneration with potential therapeutic relevance for AD, but studies of their direct effects on Aβ42 are limited. Herein, we investigated five FDA-approved GLP-1RAs, and show semaglutide, tirzepatide, and liraglutide inhibit Aβ42 aggregation. Semaglutide and tirzepatide delayed Aβ42 aggregation by targeting the primary nucleation microscopic step, with submicromolar IC50 values for primary nucleation (KIP). Liraglutide was highly effective at suppressing primary nucleation with a very low KIP value, and it demonstrated an additional modest inhibition of secondary nucleation. Consistent with a dominant effect on primary nucleation, Aβ42 formed β-sheet-rich fibrils in the presence of these GLP-1RAs. Aβ42 fibrils formed with semaglutide or tirzepatide had morphological properties and templating efficiencies that were similar to unmodified fibrils, while liraglutide significantly reduced fibril maturity, increased fibril tortuosity and length, and attenuated the ability of fibrils to passively self-replicate whether they were formed in the presence of liraglutide or exposed to this GLP-1RA after their formation. These results provide molecular-level insight into how specific GLP-1RAs can selectively target the fundamental steps governing toxic Aβ42 aggregation. Further studies are warranted to determine if current or next-generation anti-amyloid GLP-1RAs can delay or prevent AD through multifaceted protective mechanisms, including the direct inhibition of Aβ42 aggregation.

Methyl Proton Spin Relaxation (R2/R1) Enables Sensitive Detection of pH-Dependent Oligomerization in GLP-1 Analogs.

Jiaqi Lu, Eric Pang, Kang Chen

Liquid buffer pH influences the peptide higher order structure (HOS), including oligomerization, with important implications for peptide drug formulation development and stability control. Although dynamic light scattering (DLS) and diffusion-ordered spectroscopy (DOSY) NMR are commonly used to assess particle size (e.g., radius r) through measurement of translational diffusion coefficients (Dt), their sensitivity to subtle pH-dependent oligomerization changes can be limited. Here, using glucagon-like peptide-1 (GLP-1) analogs liraglutide and semaglutide as model peptides, we introduce the methyl proton spin relaxation rate ratio (R2/R1) as a sensitive NMR metric for detecting pH-dependent changes in peptide oligomerization. Diffusion coefficients measured using DLS and DOSY-NMR exhibited an overall increasing trend from pH 6.6 to 8.5, consistent with a shift toward smaller oligomers in basic solution; however, insignificant differences (p value > 0.05) were observed between pH 7.1 and 8.5 for liraglutide and between pH 6.6 and 8.2 for semaglutide. In contrast, the methyl proton R2/R1 decreased significantly with increasing pH, even within the narrow pH range of 7.1-7.7 (p value < 0.05), demonstrating smaller oligomer formation and less exchange at basic pH. The improved sensitivity arises because R2/R1 depends on both rotational diffusion (Dr ∝ r-3) and exchange kinetics, whereas DLS and DOSY depend on Dt (∝ r-1). Consequently, the R2/R1 metric offers enhanced discriminatory power for resolving subtle pH-dependent peptide oligomerization in solution and serves as a practical analytical approach for peptide formulation development and stability control.

Glucagon-like peptide-1 receptor agonists in psoriasis and psoriatic arthritis: emerging evidence and future research opportunities.

Giovanni Ciancio, Beatrice Maranini, Gilda Sandri +5 more

Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic immune-mediated diseases often associated with obesity, metabolic syndrome, and type 2 diabetes mellitus. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for T2DM, exert both metabolic and anti-inflammatory effects, which may offer therapeutic benefits for psoriatic disease, particularly in the early stages of PsA.

Aggregation-driven expression of liraglutide precursors using engineered mini-tags in Escherichia coli.

Pavan Reddy Regatti, Firdose Syed, Ramesh V Matur +1 more

Glucagon-like peptide-1 (GLP-1), a 31-amino acid incretin hormone, is widely used in the treatment of type 2 diabetes mellitus due to its glucose-dependent insulinotropic activity. However, its small size makes it highly prone to proteolytic degradation in microbial expression systems such as Escherichia coli, leading to reduced manufacturing yield. While fusion to cleavable protein tags can improve peptide stability during purification, excessively large tags often compromise the overall yield, especially when the target peptide is smaller than the fusion partner. To overcome this limitation, we have engineered 11 cleavable fusion tag constructs (LP1-LP11) for recombinant expression of Arg34-GLP-1(7-37) (liraglutide precursor) in E. coli. The 11 constructs differed only in the tags. The expression vector contained a T7 leader sequence, affinity tags (6×His/6×Arg), inclusion body tags (11-125 amino acids), and TEV protease cleavage sites. Among the 11 tags, LP8 with a compact 4.0 kDa tag achieved the highest expression, yielding 133 mg/L of fusion protein and a calculated liraglutide precursor yield of 60 mg/L based on mass fraction (45% of fusion mass), with an actual recovered yield of 14.6 mg/L after RP-HPLC purification, largely due to efficient inclusion body formation (>95% insolubility) and enhanced translational initiation driven by the T7 leader sequence. The purified peptide's identity and sequence integrity were confirmed by LC/MS analysis. The primary advantage of this approach is mass fraction optimization which focuses on minimizing fusion-tag mass to maximize yield relative to the tag size without compromising inclusion-body formation thereby providing a scalable and economical approach for GLP-1 analogs and potentially other peptide-based biopharmaceuticals.

GLP-1 Receptor Agonists, Fertility Restoration, and Reproductive Safety in Women of Reproductive Age: A Narrative Review.

Malak Moones Abedi, Mohamedanas Mohamedfaruk Patni, Arshiya Nasreen Bint Shajahan +8 more

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for the management of obesity and type 2 diabetes, particularly among women of reproductive age. Emerging evidence suggests potential effects on ovulation, fertility, and pregnancy outcomes. This narrative review aims to synthesize current evidence on the reproductive safety of GLP-1RAs, with a focus on their implications for conception, unintended pregnancy, and maternal-fetal outcomes. Methods: A narrative literature review was conducted using PubMed and relevant bibliographic sources to identify studies published between 2020 and 2025. The search included clinical trials, observational studies, registry data, case reports, and selected preclinical evidence. Studies addressing reproductive outcomes, including ovulation, fertility, pregnancy exposure, and fetal safety, were included. Evidence was synthesized descriptively in accordance with recommended approaches for narrative reviews. Results: Available evidence indicates that GLP-1RAs may improve ovulatory function and menstrual regularity, particularly in women with obesity or polycystic ovary syndrome, potentially increasing the likelihood of conception. However, human data on pregnancy exposure remain limited. While current evidence does not consistently demonstrate a strong teratogenic signal, findings are based on small samples and heterogeneous study designs. Concerns persist regarding unintended pregnancies due to improved fertility and the absence of robust safety data during early gestation. Conclusions: GLP-1RAs present a complex clinical scenario in women of reproductive age, with potential benefits for metabolic and reproductive health but uncertain safety during pregnancy. Clinicians should exercise caution, provide appropriate contraceptive counseling, and carefully weigh the risks and benefits when prescribing these agents. Further large-scale, prospective studies are needed to clarify reproductive safety and inform evidence-based clinical guidelines.

A multi-organ atlas of microcirculatory signatures for systemic profiling of diabetic and therapeutic states.

Yuan Li, Weiqi Liu, Yinguyu Wang +5 more

Microcirculatory deterioration in diabetes mellitus causes severe organ-specific complications, yet a systemic understanding of its cross-organ pathophysiology remains elusive due to a lack of comprehensive data. To address this gap, we present a high-dimensional dataset mapping microhemodynamic and oxygenation profiles across six organs in murine models of health, pre-diabetes, and type 1 and 2 diabetes. Structured as a third-order tensor, the dataset comprises 10-parameter physio-signatures for each condition, documenting responses to insulin and the GLP-1 receptor agonist liraglutide at one- and two-week endpoints. Our resource enables direct deconvolution of disease- and organ-specific signatures and provides a quantitative platform for comparing therapeutic pharmacodynamics. We propose a vectorial and tensorial analytical framework to dissect systemic patterns, quantify disease perturbation, and identify significant drug-organ interactions. Our foundational dataset is intended to catalyze the development of system-level computational models for managing diabetic microvascular disease.

Do GLP-1 receptor agonists improve insulin sensitivity and reduce lipid accumulation in skeletal muscles and the liver independent of weight loss?

Adrian Kołakowski, Monika Karczewska-Kupczewska

Increased body mass index and excessive lipid accumulation are associated with enhanced production of toxic lipid species and impairedoxidation of free fatty acids (FFAs), a phenomenon defined as lipotoxicity. It is an important predictor of etabolic disorders such astype 2 diabetes (T2D). Increased lipid accumulation leads to decreased glucose uptake in skeletal muscle and enhanced hepatic glucoseproduction. Thus, ectopic fat accumulation impairs insulin signalling and decreases insulin sensitivity (IS). Scientific data demonstratethat glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can improve IS and decrease lipid accumulation in peripheral tissues mainlythrough weight loss. However, experimental studies indicate that GLP-1 RAs exert direct effects on glucose and lipid metabolic pathways,although the precise mechanisms remain incompletely understood. GLP-1 RAs may directly modulate fatty acid β-oxidation, lipogenesis,and 5'-AMP-activated protein kinase (AMPK) phosphorylation. In this review, we discuss the mechanisms by which liraglutide and subcutaneoussemaglutide affect IS and lipid accumulation in key insulin-responsive tissues.

Anti-Inflammatory and Anabolic Effects of Liraglutide on 3D Inflammatory Osteoarthritic Spheroid and Scaffold Models of Human Chondrocytes.

Eda Ciftci, Sophie C Eberlein, Sibylle Grad +3 more

Osteoarthritis (OA) is a prevalent age-related joint disease characterized by low-grade inflammation and progressive cartilage degeneration. Liraglutide, a glucagon-like peptide-1 receptor agonist approved for diabetes and obesity, has shown anti-inflammatory and chondroprotective effects in preclinical OA models, but its effects in human 3D chondrocyte systems remain unclear.

Obesity Management: Pharmacotherapy.

Morgan A Rhodes, A Miles Scott, Matthew Nodelman +1 more

Anti-obesity drugs should be offered as initial treatment of overweight and obesity for adults with weight-related comorbidities and for those at high risk of complications, and as a component of first-line treatment for patients with obesity and overweight without comorbidities. Currently, US Food and Drug Administration-approved drugs for obesity include centrally acting drugs, gastrointestinal lipase inhibitors, and incretin mimetics. Other drugs are used off-label to promote weight loss. The incretin mimetics, glucagon-like peptide-1 receptor agonists (eg, semaglutide, liraglutide) and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor ago- nist (ie, tirzepatide), demonstrate the greatest weight loss benefits, with tirzepatide achieving reductions exceeding 20% in some patients. Drug selection should be individualized based on comorbidities (eg, cardiovascular disease, obstructive sleep apnea), cost, and patient preference. Despite growing evidence of benefit, barriers (eg, prescriber hesitancy, high costs, limited insurance coverage) persist. With multiple drugs in development, continued innovation in pharmacotherapy management offers promise, but expanding education and access remains critical to improving obesity care.

MC4R-related monogenic obesity in children: insights from 2 cases.

Dhivya Shanmugam, Subbiah Sridhar, Nandini Kuppusamy +3 more

Childhood and adolescent obesity are growing global health concerns, with genetic factors playing an important role. Despite the increasing prevalence of obesity in India, monogenic obesity remains underdiagnosed. We report 2 cases of early-onset morbid obesity due to melanocortin-4 receptor (MC4R) gene mutation. Case 1 was a 5-year-old boy who presented with severe hyperphagia and rapid weight gain since infancy. Case 2 was a 12-year-old girl who presented with progressive obesity, hyperphagia, and bilateral genu varum. Both patients exhibited severe insulin resistance with no syndromic stigmata. Genetic analysis confirmed a homozygous MC4R mutation in both cases. They were managed with a multidisciplinary approach that included dietary modification, structured physical activity, and pharmacotherapy using the glucagon-like peptide-1 analog liraglutide and metformin. Both cases showed a satisfactory response to liraglutide. These case reports highlight the point at which monogenic obesity can be clinically suspected and distinguished from syndromic obesity. Moreover, they underscore the role of genetic testing for monogenic obesity and the targeted therapies in its management.

The Effects of Exercise Combined with Pharmacotherapy on Body Composition and Metabolic Parameters in Overweight/Obese Adults: A Meta-Analysis and Network Pharmacology Study.

Tianhang Peng, Wanyuan Liang, Ju Wei +3 more

Overweight and obesity are major global health issues. Traditional interventions have limited efficacy, while pharmacological treatments are hindered by side effects and weight rebound. This study evaluates the effects of combined exercise and medication on body composition and metabolic health in overweight/obese adults, using network pharmacology to explore potential synergistic mechanisms.

Clinical Characteristics of Users of Weight Loss Drugs: Population-Based Case-Control Study.

Inger Johanne Bakken, Paz Lopez-Doriga Ruiz, Kari Furu +6 more

To investigate the clinical characteristics of weight loss drugs (WLDs) users in Norway.

Three-year changes in renal function after switching from injectable GLP-1 receptor agonists to oral semaglutide in Japanese patients with type 2 diabetes: a retrospective cohort study.

Satoru Takashima, Kanji Terui, Fukuko Yamada +1 more

While the FLOW trial established the renoprotective effects of subcutaneous semaglutide, real-world evidence regarding the long-term renal effects of therapeutic switching from injectable glucagon-like peptide-1 receptor agonists (GLP-1RAs) to oral semaglutide remains limited. We evaluated long-term changes in renal function following this therapeutic switch.

Exploring the off-label use of liraglutide in the treatment of obesity: a review.

Carla Bruna Amorim Braga, João Paulo Viana Araújo Segundo, Carlos Alberto Alves Dias Filho

Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, has been used off-label for the treatment of obesity due to its considerable weight-reducing effects. This integrative review evaluated experimental studies in humans in order to explore the pharmacological mechanisms, metabolic effects, and the various clinical responses involved in the use of this drug. The research was conducted in the PubMed database, considering articles written in English and published in the last 10 years, with 9 studies included. The studies demonstrated that liraglutide is effective for weight loss and acts through gastric emptying, modulation of satiety, and influences on brain regions. Additionally, genetic polymorphisms may interfere with the clinical response. Regarding metabolic effects, improvements in glycemia and hepatic steatosis were observed, as well as possible anti-inflammatory action and improvement in blood pressure and lipid profile. The efficacy of liraglutide does not depend on variables such as BMI (Body Mass Index) or age; however, alcohol consumption and proper adherence to treatment may influence clinical outcomes. The main adverse effects, such as nausea and constipation, were well tolerated. Therefore, liraglutide can be considered a promising alternative in the management of obesity, especially in populations with multiple metabolic risk factors.

The National Psoriasis Foundation Primer on GLP-1 Receptor Agonists in Psoriasis: A Review.

Samip Sheth, Joseph F Merola, Brittany N Weber +12 more

Psoriasis is a chronic immune-mediated disease associated with cardiovascular, metabolic, musculoskeletal, psychiatric, hepatic, kidney, and pulmonary comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are approved by the US Food and Drug Administration for type 2 diabetes, obesity, cardiovascular risk reduction, chronic kidney disease, obstructive sleep apnea, and metabolic dysfunction-associated steatohepatitis-conditions common in psoriasis. Emerging evidence suggests GLP-1 RAs and dual glucose-dependent insulinotropic polypeptide/GLP-1 agonists may improve psoriatic skin disease, partly through immune modulation. If confirmed in larger randomized clinical trials, GLP-1-based therapies may offer an opportunity to address both cutaneous disease and cardiometabolic comorbidities. This primer from the US National Psoriasis Foundation Medical Board sought to provide an evidence-informed narrative synthesis and practical considerations to introduce dermatologists to GLP-1 RAs for psoriasis treatment.

THR-β Agonists vs Incretin Therapies for Noncirrhotic Metabolic Dysfunction-Associated Steatohepatitis (MASH): A Biopsy-Anchored Systematic Review With Grading of Recommendations Assessment, Development and Evaluation (GRADE) Certainty.

Amirah A Alzaki, Mohammed Z Alqahtani, Eiman Aman +8 more

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease now targeted by new pharmacotherapies, including the thyroid hormone receptor beta (THR-β) agonist resmetirom, glucagon-like peptide-1 (GLP-1) receptor agonists (semaglutide, liraglutide), and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide. Each acts through distinct metabolic pathways, yet no head-to-head comparisons exist. The aim of this study was to systematically review randomized controlled trials assessing the efficacy and safety of resmetirom, GLP-1 receptor agonists, and dual GIP/GLP-1 receptor agonists in adults with biopsy-confirmed, non-cirrhotic MASH (F2-F3), and to evaluate the certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020, seven eligible randomized controlled trials (RCTs) involving 3,796 participants were identified through PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and trial registries (inception to October 2025). The comprehensive methodological protocol was filed in PROSPERO (reg. no. CRD420251230032) before the commencement of data collection. Data were extracted in duplicate; risk of bias was assessed using Cochrane Risk of Bias 2 (RoB 2), and certainty of evidence was graded using GRADE. Due to heterogeneity, the data were synthesized qualitatively. The included studies were RCTs of adults with biopsy-confirmed, non-cirrhotic MASH (F2-F3) treated with resmetirom, GLP-1 receptor agonists, or GIP/GLP-1 receptor agonists, while non-randomized studies and pediatric and cirrhotic populations were excluded. This study is limited by the absence of head-to-head trials comparing the three drug classes, as well as by heterogeneity across the included studies, which precluded meta-analysis. The results showed that all active therapies outperformed placebo on at least one biopsy-anchored endpoint. Resmetirom improved both MASH resolution and fibrosis at 52 weeks, with marked low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) reductions but minimal weight change. Semaglutide achieved dose-dependent histologic and metabolic benefits, culminating in dual-endpoint improvement in the phase 3 ESSENCE trial. Liraglutide improved resolution in a small trial, while tirzepatide achieved both endpoints with large, dose-related weight loss. Non-invasive biomarkers paralleled histology, and adverse events were predominantly mild gastrointestinal effects. GRADE assessments indicated low certainty for between-class differences in histologic outcomes, high certainty favoring incretin therapies for weight reduction, and moderate certainty favoring resmetirom for lipid lowering. In conclusion, resmetirom, semaglutide, and tirzepatide each demonstrate clinically meaningful efficacy and tolerability in non-cirrhotic MASH, with distinct metabolic profiles, resmetirom as a lipid-centric, weight-neutral therapy and incretins as weight-centric, pleiotropic agents. Further direct-comparison trials are warranted to clarify their relative benefits on histology and cardiometabolic outcomes.

Non-arteritic anterior ischaemic optic neuropathy incidence in placebo-controlled clinical trials of liraglutide or semaglutide.

Tina Vilsbøll, Dikshit Arun Kumar, Lloyd Paul Aiello +3 more

Risk of non-arteritic anterior ischaemic optic neuropathy (NAION) following exposure to glucagon-like peptide-1 receptor agonists (GLP-1RAs) in people with type 2 diabetes and/or obesity remains unclear. The aim of this study was to investigate NAION incidence across randomised placebo-controlled trials evaluating the GLP-1RAs liraglutide and semaglutide.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) in dermatology: cutaneous adverse events and emerging efficacy in inflammatory skin diseases.

Meng Jie Ho, Choon Fong Liew, Nguan Soon Tan +2 more

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and next-generation incretin therapies are increasingly used for diabetes and obesity, yet cutaneous adverse events remain incompletely characterized. New-onset dermatological manifestations after GLP-1RA initiation such as rash or alopecia may be misattributed to baseline inflammatory skin disease rather than drug-induced toxicity.

Familial partial lipodystrophy type 2 associated with a novel LMNA variant (c.604G>C; p.Glu202Gln): a Colombian family case series.

Carolina Mendoza, Raquel Cano, Luis Burgos +1 more

Familial partial lipodystrophy type 2 (FPLD2) is a rare autosomal dominant laminopathy caused by LMNA gene variants. It is characterized by progressive gluteofemoral lipoatrophy and severe metabolic derangements, including insulin resistance and metabolic dysfunction-associated steatotic liver disease.

Glucagon-Like Peptide-1 Receptor Agonists for Bile Acid Diarrhea: Emerging Evidence and Clinical Implications.

Eunice K Omeludike, Cherechi O Nwabueze, Nneoma Ubah +7 more

Bile acid diarrhea (BAD) is an underrecognized cause of chronic diarrhea that makes a significant contribution to the symptom burden and impaired quality of life. Despite increasing awareness, BAD is frequently misdiagnosed as diarrhoea-predominant irritable bowel syndrome (IBS-D), leading to delayed diagnosis and incomplete symptom control. Current management relies primarily on bile acid sequestrants, which are effective for many patients but limited by poor tolerability, variable adherence, and incomplete response in a subset, prompting interest in alternative therapeutic approaches targeting bile acid dysregulation. Advances in understanding enterohepatic signaling have highlighted the role of the farnesoid X receptor-fibroblast growth factor 19 (FXR-FGF19) axis in regulating bile acid synthesis, secretion, and motility. In parallel, glucagon-like peptide-1 (GLP-1) receptor agonists, which are commonly used in the treatment of metabolic diseases, affect gastrointestinal motility, secretion, and neurohormonal signaling by mechanisms that overlap with those that are implicated in BAD. Emerging clinical studies, including randomized trials comparing GLP-1-based therapy with established bile acid sequestrants, have begun to explore their potential role in BAD, although the current evidence base remains limited and investigational. This narrative review synthesizes peer-reviewed evidence examining the biological rationale, diagnostic context, and clinical data relevant to GLP-1 receptor agonists in BAD. Literature was identified primarily by PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE) searches supplemented by manual screening of reference lists of key reviews and clinical studies and integrated narratively because of heterogeneity of study design, exposure definitions, and outcome measures. Current evidence suggests that GLP-1 receptor agonists represent a biologically plausible area of investigation for selected patients with persistent symptoms despite standard therapy. This review does not advocate routine clinical use but aims to contextualize emerging BAD-specific and mechanistic data to inform hypothesis generation, patient selection, and future research. Available data are still limited, and GLP-1 receptor agonists have not been established as a treatment for BAD. Further prospective studies with standardized outcomes are needed to clarify their role and inform evidence-based clinical practice.

Mapping Global Research on Adverse Effects of GLP-1 Receptor Agonists (2006-2025): A Scopus-Based Bibliometric and Thematic Analysis.

Riad Mohammed Abdelrahman, Taha Hussein Musa, Ismail Adam Arbab +5 more

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for managing type 2 diabetes and obesity. As their clinical applications expand, interest in their safety and adverse effects has grown. This study provides a comprehensive bibliometric analysis of global research trends, collaboration patterns, and thematic evolution on GLP-1RA-related adverse effects from 2006 to 2025. This study is a bibliometric analysis. Data were extracted from the Scopus database and analyzed using Bibliometrix (R package) and VOS viewer. Indicators assessed included publication and citation metrics, institutional productivity, and keyword co-occurrence and mapping. Correlations were evaluated using Pearson and Spearman tests, and the Durbin-Watson statistic was applied to assess the independence of residuals. A total of 1075 articles published in 389 journals were identified, authored by 6068 researchers across 85 countries. The annual growth rate was 32.06%, with no single-author papers and 34.23% international co-authorship, indicating strong global collaboration. The United States (30.5%), the United Kingdom (10.6%), and Denmark (7.8%) led in publication output and total citations. Institutional analysis identified Novo Nordisk A/S (60 papers, 11 207 citations) and Eli Lilly & Co. (45 papers, 9948 citations) as the most influential contributors. Diabetes, Obesity and Metabolism published the most articles (n = 106), followed by Diabetes Care and The Lancet Diabetes & Endocrinology. Significant correlations were found between article count and h-index (r = .677, P < .001) and total citations (r = .779, P < .001). Keyword analysis revealed 2 main thematic clusters-one pharmacological (drug safety, efficacy, liraglutide, semaglutide) and 1 clinical (human, male, female, adult)-with an emerging focus on population-specific safety since 2021. Research on GLP-1RA-related adverse effects has expanded rapidly, shaped by strong international collaboration and industry-academic partnerships. Future efforts should prioritize balanced global participation, real-world safety data, and mechanistic insights to inform clinical practice and pharmacovigilance.

Cardiovascular outcomes of glucagon-like peptide-1 receptor agonists: A systematic review.

Nicoline Bihelek, Sarah Burke, Arden R Barry

To identify and evaluate cardiovascular outcome trials for glucagon-like peptide-1 receptor agonists (GLP1RAs) in various patient populations, including those with or without type 2 diabetes (T2D).

Cav3.1 is a neuronal leucine sensor that mediates satiety and weight loss in response to dietary protein.

Anthony H Tsang, Nicholas Heeley, Constanza Alcaino +18 more

Dietary protein promotes satiety and weight loss, yet how appetite-regulating neurons sense dietary protein remains poorly understood. Here, we show that Cacna1g, which encodes the T-type voltage-gated calcium channel Cav3.1, is enriched in hypothalamic leucine-sensing neurons and mediates neuronal leucine sensing. Pharmacological inhibition of Cav3.1 blunts leucine-induced activation of pro-opiomelanocortin (POMC) neurons in cultured neurons and brain slices, thereby suppressing the anorectic response to hypothalamic leucine in vivo. Genetic deletion of Cacna1g in POMC neurons abolishes the appetite- and weight-suppressive effects of high-protein feeding. Mechanistically, leucine binds a hydrophobic pocket of Cav3.1 and lowers its threshold for voltage-dependent activation. Finally, pharmacological activation of mediobasal hypothalamic Cav3.1 promotes weight loss in diet-induced obese mice and potentiates responses to anorectic agents, including liraglutide. Together, these findings establish hypothalamic Cav3.1 as a neuronal leucine sensor and nominate it as a tractable target for anti-obesity therapy.

Clinical outcomes of glucagon-like peptide-1 receptor agonist therapy in kidney transplant recipients: a systematic review and meta-analysis.

Mehmet Kanbay, Sama Mahmoud Abdel-Rahman, Mustafa Guldan +5 more

Metabolic complications after kidney transplantation (KT) significantly affect graft and patient survival. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer cardio-renal benefits in the general population, but evidence in KT recipients remains limited.

Dynamics of Body Composition and Metabolic Risk in Adolescents With Obesity Under GLP-1 Receptor Agonist Therapy.

Adar Lopez, Liat Perl, Eyal Cohen-Sela +9 more

To explore changes in body composition in adolescents with obesity treated with glucagon-like peptide-1 receptor agonist (GLP-1 RA) and their association with metabolic syndrome (MetS) components.

New Horizons in Metabolic Health: Unveiling the Future of Drug Discovery and Development.

Jinshan Zhao, Quanyu Qiu, Jidong Zhang +1 more

Metabolic diseases (diabetes, obesity, NAFLD) pose a severe threat to global health, demanding innovative drug solutions.

Depressed mood and suicidal thoughts reporting with GLP-1 receptor agonists in type 2 diabetes: A WHO VigiBase study.

Mohammed Aboukaoud, Bosmat Hoch, Mark Weiser +1 more

Evidence regarding depression and suicidality with glucagon-like peptide-1 receptor agonists (GLP-1RAs) remains inconsistent, particularly in patients with type 2 diabetes mellitus (T2DM) and underlying affective vulnerability.

GLP-1 receptor agonists in stroke prevention: a narrative review on emerging therapeutic frontiers.

Rahul Chikatimalla, Ashka Shah, Twinkle Shah +4 more

To evaluate the current evidence supporting the cerebrovascular protective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in individuals with type 2 diabetes mellitus (T2DM), and to outline their mechanisms of action in stroke prevention.

Effect of Incretin-Based and Nonpharmacologic Weight Loss on Body Composition : A Systematic Review.

John A Batsis, Alessandro Gavras, Danae C Gross +12 more

Incretin-based therapies induce substantial weight loss and are widely prescribed; disproportionate losses in fat-free mass (FFM) and skeletal muscle are a concern.

Insights from changes in NDEV biomarkers of metabolism: Effects of PPARγ and GLP1 receptor agonists on brain metabolism.

Audrey Evers, Kathleen Watson, Fahim Abbasi +4 more

Insulin resistance (IR) is implicated in central nervous system disorders, including depression and Alzheimer's disease (AD).

Cardiometabolic Profiles of Oral and Subcutaneous Glucagon-Like Peptide-1 Receptor Mono-Agonists in Adults With Overweight or Obesity: A Systematic Review and Network Meta-Analysis.

Ying Lu, Jiajie Chen, Yuqing Guo +6 more

To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA).

Approved weight loss drugs for obesity with a thorough emphasis on GLP-1 agonist medications: A systematic review.

Praveen Gunasekaran, Pugazhendi Inban, Ashita Agrawal +5 more

Obesity is a worldwide health concern linked to cardiometabolic comorbidities such as type 2 diabetes, hypertension, dyslipidemia, and heart disease. The management of obesity using pharmacotherapy, especially with GLP-1 receptor agonists and dual incretin agents, has proven successful not only for weight loss but also for gaining control of the metabolic components of the disease. Thus, it is pertinent to analyse the GLP-1-based anti-obesity medications to examine cardiometabolic efficacy and safety using weight loss, glycemic control, cardiometabolic, gastro-intestinal tolerability, and serious adverse events as the primary variables.

Glucagon-Like Peptide-1 Receptor Agonists in Patients with Heart Failure with Reduced Ejection Fraction.

Joseph Kassab, Mark H Drazner, Jennifer T Thibodeau

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve cardiovascular outcomes in obesity and HFpEF; however, their safety and efficacy in heart failure with reduced ejection fraction (HFrEF) remain uncertain.

Glucagon-Like Peptide-1 Receptor Agonists: Their Potential Role in Prediabetes.

Theodoros Panou, Evanthia Gouveri, Djordje S Popovic +2 more

Prediabetes is a frequently occurring condition with increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established antidiabetic agents, also used to treat obesity. There is limited, yet promising evidence on their use in prediabetes. T2DM was less frequent among subjects on liraglutide, semaglutide and tirzepatide compared with the control arm. Delayed progression to T2DM has also been observed. Furthermore, normoglycaemia was achieved for subjects on liraglutide (up to 66%), semaglutide (up to 81%) and tirzepatide (up to 93.3%). However, this effect was only partially sustained following drug withdrawal. GLP-1RAs have led to modest decreases in glycated haemoglobin (HbA1c), fasting glucose, weight and fat mass loss, as well as increased insulin sensitivity and improved β-cell glucose-insulin dynamics. Decreased risk for atherosclerotic cardiovascular disease and heart failure was also demonstrated, mostly for subjects on tirzepatide. There is experimental evidence on improvements in liver dysfunction, pointing to potential benefits for metabolic dysfunction-associated steatotic liver disease (MASLD) in prediabetes. The safety profile was acceptable with mild-to-moderate gastrointestinal adverse effects being mostly reported. Future large randomised controlled trials are needed to ascertain the exact role of GLP-1RAs in prediabetes.

Oral Delivery of Liraglutide Formulated with PLGA for Sustained Obesity Management.

Nipeng Chen, Zhipeng Zeng, Xiaoyu Ji +3 more

Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated substantial efficacy in improving glycemic control and reducing body weight. However, subcutaneous injection is poorly adherent for patients. To improve treatment compliance, we developed a poly(lactic-co-glycolic acid) (PLGA)-based nanovesicle (PLGA-Lira-NV) system for the oral delivery of Lira using a double-emulsion solvent evaporation technique. The optimized formulation yielded a narrow size distribution and high encapsulation efficiency (>95%). In vitro release studies showed that PLGA-Lira-NVs remained relatively stable under acidic conditions (pH 1.2 to 6.8) and exhibited sustained drug release in a neutral environment (pH 7.4), enabling protection of the fragile peptide in the stomach and controlled release after crossing the intestine. Following oral administration to obese mice (10 mg/kg), PLGA-Lira-NVs achieved prolonged glycemic control for up to 72 h. Notably, body weight decreased to 83% of baseline after 12 days, outperforming the subcutaneous injection (free Lira) group (88%). The consistent trend toward weight reduction confirms the sustained-release properties of PLGA nanocarrier for Lira, highlighting its potential to reduce dosing frequency and improve patient compliance. Collectively, these findings underscore the promising potential of PLGA nanovesicles as an oral delivery platform for peptide therapeutics.

Disproportionality Analysis of Tirzepatide vs. Semaglutide and Liraglutide: System Organ Class-Level Post-Marketing Reporting Patterns in EudraVigilance.

Ruxandra Cristina Marin, Cosmin Mihai Vesa, Delia Mirela Tit +2 more

Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist, introduces a mechanistically distinct approach within incretin-based therapies. While its efficacy is established, real-world data comparing post-marketing safety with established GLP-1 receptor agonists remain limited. This study assessed System Organ Class (SOC)-level reporting patterns for tirzepatide versus semaglutide and liraglutide using EudraVigilance data. Aggregated individual case safety reports (ICSRs) were analyzed using pairwise disproportionality analyses based on a case/non-case approach. Reporting odds ratios (RORs) with 95% confidence intervals were calculated. False discovery rate (FDR) correction using the Benjamini-Hochberg procedure and sensitivity analyses restricted to serious and healthcare professional-reported cases were performed to assess robustness. After FDR adjustment, 20 SOCs were significant in tirzepatide-semaglutide and 23 in tirzepatide-liraglutide comparisons; eight SOCs remained significant across all analytical conditions. Compared with semaglutide, tirzepatide showed higher reporting for immune (ROR 1.97, 95% CI 1.75-2.21) and hepatobiliary disorders (ROR 1.71, 95% CI 1.61-1.82). Versus liraglutide, higher odds occurred for musculoskeletal (ROR 2.02, 95% CI 1.85-2.21) and psychiatric disorders (ROR 2.14, 95% CI 1.99-2.30), and lower odds for neoplasms (ROR 0.28, 95% CI 0.26-0.31). Tirzepatide shows heterogeneous reporting patterns compared with GLP-1 receptor agonists, with consistent excess reporting for hepatobiliary, immune, and musculoskeletal disorders. These findings are hypothesis-generating and warrant confirmation in exposure-adjusted studies.

Comparison of pharmacotherapies for obesity with sleeve gastrectomy: a network meta-analysis and systematic review.

Zachary Omeh, Tahira Khan, Olalekan Uthman +1 more

Tirzepatide, a glucagon-like peptide-1 receptor agonist (GLP1RA) and glucose-dependent insulinotropic-peptide (GIP), has shown efficacy regarding weight-loss.

Target-mediated drug disposition modeling of liraglutide in rats: Implications of target engagement for pharmacodynamic predictions.

Sungmin Song, Joonhee Kim, Siyeon Kim +2 more

Target-mediated drug disposition (TMDD) is a pharmacokinetic phenomenon in which high-affinity binding to specific receptors leads to nonlinear pharmacokinetics. This study evaluated the pharmacokinetics and pharmacodynamics of the GLP-1 receptor agonist liraglutide in normal and diabetic rats, and developed a TMDD model to mechanistically link receptor dynamics to pharmacological outcomes. Liraglutide was administered intravenously across a wide dose range (0.005-0.8 mg/kg in normal rats; 0.005-0.2 mg/kg in diabetic rats). Plasma concentrations of liraglutide were determined using validated LC-MS/MS methods. Noncompartmental analysis revealed dose-dependent increases in clearance and volume of distribution at lower doses, consistent with TMDD behavior. A TMDD model adequately captured the observed concentration-time profiles across all dose levels. In diabetic rats, the pharmacodynamic response, measured as blood glucose reduction, exhibited a saturating relationship with both dose and plasma exposure (AUC). In contrast, the individually predicted AUC of the drug-receptor complex (AUCD-R complex) showed a linear correlation with the area under the effect curve (AUEC; β = 0.93, 95% CI 0.64-1.21), suggesting that receptor occupancy may serve as a more relevant determinant of pharmacodynamic response than plasma drug concentration. Simulations further revealed dose-dependent receptor depletion and saturable drug-receptor complex formation, providing mechanistic explanations for the prolonged pharmacological effects and nonlinear exposure-response relationship of GLP-1 receptor agonists. These findings support the utility of TMDD modeling for linking receptor dynamics to pharmacodynamic outcomes and provide a translational framework for rational dose optimization of peptide therapeutics.

Targeting Multiple Gut-Brain Pathways in Obesity: Rationale for Combination Pharmacotherapy.

Alexander D Miras, Muzamil Hussain

As a disease of energy dysregulation, obesity involves metabolic, hormonal, and neural factors, the interconnection of which is referred to as the "gut-brain axis."

Incretin-Based Therapies for the Treatment of Binge Eating-A Systematic Review.

Raechel T White, Penelope Henriquez, Britnee Innocent +2 more

Binge eating disorder (BED) is a common psychiatric condition associated with psychological and cardiometabolic morbidity. Psychotherapy remains a core treatment modality while pharmacologic agents such as lisdexamfetamine, selective-serotonin reuptake inhibitors (SSRIs), and topiramate demonstrate variable efficacy and tolerability. Incretin therapies-specifically glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA-originally developed for type 2 diabetes mellitus (T2DM) and obesity, are an emerging therapy of interest for BED due to their effects on satiety, appetite regulation, and reward-driven eating. This systematic review examines current data surrounding the efficacy of incretin therapies in treating BED and discusses potential mechanisms underlying their effects.

Glucagon-like peptide-1 receptor agonist use and clinical outcomes after posterior cervical spinal fusion for degenerative pathologies: A large cohort retrospective analysis.

Christian Rajkovic, Ankita Jain, Mahnoor Shafi +6 more

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as potentially impactful agents in improving spinal fusion outcomes. While several recent studies have investigated the effect of these agents on lumbar spinal procedures, the current evidence of the impact of these agents on cervical spinal fusion is limited. This study aims to investigate the impact of GLP-1RA use on perioperative clinical outcomes of posterior cervical spinal fusion.

Real-World Effectiveness and Safety of Tirzepatide, Semaglutide, and Liraglutide in Adults with Overweight or Obesity without Diabetes: A Comparative Study.

Serap Cetiner

Obesity is a chronic metabolic disease associated with substantial cardiometabolic risk and long-term morbidity. Although randomized controlled trials have demonstrated the efficacy of incretin-based therapies, real-world comparative data in adults with overweight or obesity without diabetes remain limited. Real-world studies provide complementary evidence by capturing treatment effectiveness, tolerability, dose escalation, and adherence in routine clinical practice.

Tirzepatide-Induced Liver Injury: A Rare Complication.

Lauren D Spaeth, Kim M Jordan, Mariah P Barlow +1 more

Tirzepatide is widely prescribed and generally considered safe. The objective of this report is to describe a patient with tirzepatide-induced liver injury and increase awareness of this rare complication.

Weight Loss With GLP-1 Agonists in Nondiabetic Adults: Systematic Review and Network Meta-Analysis.

Michael Lim, Pooja Gokhale, Akwasi Akosah +1 more

Two glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (semaglutide and liraglutide) and one dual agonist (tirzepatide) are FDA-approved for weight loss in adults with obesity without type 2 diabetes mellitus. This systematic review and network meta-analysis aims to compare the efficacy of these agents against each other.

GLP-1 receptor agonists and immune checkpoint inhibitor therapy: a narrative review on mechanistic and clinical evidence.

Connor Frey

Obesity paradoxically increases sensitivity to immune checkpoint inhibitors (ICIs) despite elevating cancer risk, creating a clinical opportunity where metabolic dysfunction may generate a target-rich immune microenvironment. However, immunosuppressive mechanisms, including regulatory T-cells, myeloid-derived suppressor cells, and pro-inflammatory macrophages, can limit durable anti-tumor responses. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) extend beyond metabolic comorbidity management, functioning as metabolic-immunologic adjuvants capable of reprogramming the tumor microenvironment in obese patients receiving ICIs. A literature search was conducted in PubMed/MEDLINE through December 2025 using MeSH headings related to glucagon-like peptide-1 receptor agonists and immune checkpoint inhibitors. Mechanistically, GLP-1R signaling activates cAMP-PKA-AMPK pathways that suppress NF-κB-driven inflammation and promote macrophage repolarization, improving CD8 T-cell metabolic fitness, enhancing central memory formation, and reducing lipid-induced T-cell exhaustion. Real-world observational data across renal cell carcinoma, non-small cell lung cancer, colorectal cancer, and neuroendocrine neoplasms suggest improved overall survival, fewer immune-related adverse events, and lower cardiometabolic complications with concurrent GLP-1RA and ICI therapy. Pharmacovigilance concerns regarding pancreatitis, ICI-induced diabetes, and immune-related toxicities remain incompletely characterized. This review critically appraises mechanistic insights, real-world evidence, and safety considerations, proposing a translational-clinical research agenda to prospectively validate GLP-1RAs as rational adjuncts to checkpoint blockade.

Benchmarking size-exclusion chromatography columns for the analysis of therapeutic peptides and model oligonucleotides.

Mathias Buff, Alexandre Goyon, Kelly Zhang +1 more

Eleven modern size-exclusion chromatography (SEC) columns, including prototype columns designed to minimize non-specific interactions, were systematically evaluated for the analysis of peptides and oligonucleotides. Column physical properties and chromatographic performance were assessed under various mobile phase conditions. Notably, a reduced plate height close to 1 was achieved for one prototype column, representing a marked improvement over typical SEC performance (2 < hmin < 3). Mobile phase composition was optimized to balance chromatographic efficiency and analyte denaturation. The most denaturing conditions (30 % acetonitrile, 0.1 % trifluoroacetic acid) provided the best performance for linear, macrocyclic, disulfide-constrained, and lipid-conjugated peptides by effectively suppressing hydrophobic and ionic interactions. Columns with pore sizes ≥ 100 Å showed optimal performance, with UP-SW2000, Biozen dSEC-1, and BioCore SEC-120 columns (100-125 Å) yielding the best results. Column and mobile phase selection were particularly critical for hydrophobic peptides such as liraglutide and semaglutide; for these analytes, a phosphate-based mobile phase containing 20 % isopropanol was proposed to limit denaturation and potentially enable the characterization of non-covalent aggregates. For oligonucleotides, mobile phase composition had a limited impact, whereas stationary phase chemistry was decisive. Only two columns (UP-SW2000 and ACQUITY Premier SEC 125 Å) provided acceptable separations, enabling resolution of n-2 and n-3 shortmer impurities of 20-mer linear and structured oligonucleotides with resolutions close to 1. Coupling two 150-mm SEC columns in series further enhanced shortmer separation within 30 min.

Glucagon-like peptide-1 receptor agonists reduce experimental atherosclerosis progression, inflammatory biomarkers and cardiovascular events, irrespective of hyperglycaemia and obesity.

Mohamad B Kassab, Haitham Khraishah, Andrew Thrapp +16 more

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiovascular events. However, their impact on atherosclerosis and inflammation, regardless of diabetes or obesity, is unknown. Here, GLP-1 RA effects were investigated on (i) atherosclerosis burden and inflammation in vivo in rabbits and (ii) inflammatory biomarkers and major adverse cardiovascular events (MACE) in clinical subjects, adjusted for glycaemic and obesity status.

The Role of GLP1 Receptor Agonists and Multi-agonist Incretin Therapies for Specific Obesity-related Health Conditions: Evidence and Rationale for Prioritisation.

Christo Albor, Oluwaseun Anyiam, Luke D Boyle +17 more

Impact of GLP-1 and dual agonists on the incidence of new cases of physician-reported sleep apnea: a real-world study.

Beatriz S Prado, Diego R Mazzotti, André Franci +5 more

Previous studies have shown that glucagon-like peptide-1 (GLP-1) agonists and dual GLP-1/glucose-dependent insulinotropic peptide (GIP) agonists (tirzepatide) reduced severity of sleep apnea. However, whether these medications impact incidence of new cases of physician-reported sleep apnea (PRSA) is unknown.

Efficacy of Glucagon-Like Peptide-1 Receptor Agonists for Psychological Well-Being and Depressive Symptoms: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Tsung-Hsuan Hung, Chyi-Rong Chen, Chih-Wei Hsu +5 more

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for metabolic disorders. Howeve, their effects on depressive symptoms and psychological well-being remain uncertain.

Potential Antiarrhythmic Mechanisms of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs).

Jianhong Li, Kun Fu, Jiaqian Zhao +9 more

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a novel class of glucose-lowering agents that offer benefits beyond glycemic control and weight loss and are increasingly recognized for their cardioprotective benefits, including protective effects against hypertension, heart failure, myocardial infarction, and arrhythmias. Notably, GLP-1RAs have demonstrated a significant capacity to reduce arrhythmia risk not only in animal models but also in large-scale clinical trials. However, the antiarrhythmic mechanisms of GLP-1RAs remain incompletely understood. This mechanistic review synthesizes current preclinical and clinical evidence to delineate the key pathways through which GLP-1RAs may exert their antiarrhythmic effects. The primary mechanisms discussed include the attenuation of cardiomyocyte death, improvement of myocardial metabolism, and inhibition of the inflammatory response. Additional mechanisms, such as the promotion of autophagy, maintenance of ion homeostasis in cardiomyocytes, and modulation of the autonomic nervous system, are also examined. By clarifying these mechanisms, this review aims to offer novel therapeutic strategies for arrhythmia prevention, especially in the high-risk population with cardiometabolic diseases.

Emulating the LEADER trial in China: a regulatory science case study on non-interventional research.

Jun Zhao, Xiaona Xin, Yuanyuan Song +4 more

Integrating real-world evidence (RWE) into regulatory decision-making requires validation against pivotal randomized controlled trials for the same estimand. We emulated the LEADER trial using Chinese claims data to evaluate liraglutide's cardiovascular safety, assessing RWE-RCT concordance and examining the methodological adaptations and operational challenges encountered when emulating RCTs with claims data.

Cardiovascular Outcomes and Safety of GLP-1 Receptor Agonists in Elderly Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Weifei Gao, Xiaoming Cai, Xiaolu Wang +1 more

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes. However, evidence specific to elderly patients remains limited. Elderly patients with diabetes are associated with high cardiovascular (CV) risk and increased susceptibility to adverse events. Therefore, this study systematically evaluated the CV outcomes and safety of GLP-1 RAs in elderly patients with T2DM.

A septal inhibitory circuit constrains alcohol reward and mediates liraglutide's suppressive effects on alcohol intake in mice.

Yu Tian, Yutong Liu, Haiyang Jing +10 more

Alcohol use disorder (AUD) lacks effective brain-targeted treatments. Here, using mouse models, we show that glucagon-like peptide-1 receptor (GLP-1R) signaling in the dorsal lateral septum (dLS) regulates alcohol consumption and reward. Systemic administration of the GLP-1R agonist liraglutide decreased alcohol intake and ethanol-evoked dopamine release in the nucleus accumbens, requiring GLP-1R expression in the dLS. Alcohol consumption suppressed dLSGLP-1R neuronal activity, whereas liraglutide prevented alcohol-induced suppression of transient calcium dynamics. Inactivation of these neurons increased alcohol consumption and abolished the behavioral effects of liraglutide, whereas chemogenetic activation suppressed alcohol-directed behavior. Circuit-level analysis identified a local inhibitory projection from dLSGLP-1R neurons to estrogen receptor 1-expressing neurons in the ventral lateral septum (vLSEsr1 neurons), and targeted manipulation of this circuit confirmed its role in regulating alcohol intake. Together, these findings delineate a septal inhibitory circuit through which GLP-1R signaling modulates alcohol-related behaviors and highlight the dLS as a therapeutic target for AUD.

Exposure-adjusted safety and efficacy of GLP-I and GLP-1/GIP receptor agonists compared with non-GLP-I for weight management and type 2 diabetes: Based on FDA medical and statistical reports of 34 280 safety and 36 312 efficacy subjects.

Aishwarya Prasad, Anshu Arora, Arun Arora +2 more

This work aimed to contextualize glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists safety and efficacy regarding weight management (WM); we analysed Food and Drug Administration (FDA) Medical Reviews to analyse 14 medications using patient-exposure year normalization and compared GLP-1 RAs with older WM medications.

Psychiatric Adverse Events and Administration Challenges Associated with GLP-1 Receptor Agonists for Weight Loss: A Real-World Analysis.

Ali Hindi, Mohamed Mekkawy, Hala Shokr

Background: Glucagon-like peptide-1 receptor agonists are increasingly prescribed for weight loss, but concerns remain regarding adverse events beyond gastrointestinal, renal, and pancreatic effects. Understanding these risks is essential to guide safe clinical application and public health policy. The study aims to characterize psychiatric risks, administration-related adverse events, and patterns of inappropriate use associated with semaglutide, liraglutide, and tirzepatide for weight management. Methods: Disproportionality analysis using proportional reporting ratios and reporting odds ratios was conducted to detect significant signals in adverse event reports within the U.S. Food and Drug Administration Adverse Event Reporting System, identifying semaglutide, liraglutide, or tirzepatide as drugs used for weight loss while excluding gastrointestinal, renal, and pancreatic adverse events. Results: Among 40,253 adverse event reports (68.6% female; median ages: semaglutide, 62 years; liraglutide, 59 years; tirzepatide, 53 years), semaglutide demonstrated the strongest disproportionality signal for psychiatric adverse events, notably anxiety (PRR 1.34, 95% CI 1.18-1.51), depression (PRR 1.83, 95% CI 1.62-2.07), and suicidal ideation (PRR 3.44, 95% CI 2.98-3.97). Tirzepatide showed markedly higher signals for injection-site reactions (PRR 7.98, 95% CI 7.8-8.18) and inappropriate use, including incorrect dosing and off-label administration (PRR 5.98, 95% CI 5.9-6.06). Conclusions: In real-world use, semaglutide is disproportionately associated with psychiatric adverse events, whereas tirzepatide demonstrates higher rates of injection-site complications and misuse. Liraglutide presents a comparatively lower risk profile. These findings underscore the need for vigilant psychiatric monitoring, patient education on injection technique and dosing, and stronger regulatory oversight to reduce misuse of GLP-1 receptor agonists for weight loss.

New Drugs on the Block: Dietary Management and Nutritional Considerations During the Use of Anti-Obesity Medication.

Eleni C Pardali, Kalliopi K Gkouskou, Christos Cholevas +4 more

Incretin-based pharmacotherapy has rapidly transformed obesity management. However, despite its efficacy, gastrointestinal (GI) adverse events (AEs) are common and represent a major driver of treatment discontinuation. Symptoms such as nausea, vomiting, acid reflux, diarrhea, and constipation, not only impair the quality of life, but also compromise adherence, thereby limiting the real-world effectiveness of these agents. Targeted nutritional strategies may play a pivotal role in mitigating these symptoms and supporting sustained treatment. However, most clinical trials have relied on generalized lifestyle advice combined with hypocaloric dietary prescriptions, with limited integration of structured, mechanism-based nutritional counseling tailored to the physiological actions of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs. Consequently, practical guidance for clinicians and dietitians remains fragmented. The present review synthesizes the available evidence on GI AEs associated with incretin-based therapies and examines whether structured, targeted nutritional management can meaningfully reduce symptom burden. We also outline key monitoring strategies and focus on important clinical aspects for physicians and dietitians, aiming to optimize patient outcomes. In addition, we provide detailed information on the spectrum of GI AEs to guide effective management and limit intolerance. By bridging pharmacology with applied clinical nutrition, we aim to provide a pragmatic framework for improving tolerability, sustaining adherence, and translating trial efficacy into durable real-world effectiveness.

GLP-1 Receptor Agonists at the Crossroads of Circadian Biology, Sleep, and Metabolic Disease.

Ayush Gandhi, Ei Moe Phyu, Kwame Koom-Dadzie +2 more

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of type 2 diabetes and obesity, yet their actions extend beyond glycemic control and weight loss. This narrative review synthesizes current preclinical and clinical evidence examining the bidirectional relationship between glucagon-like peptide-1 (GLP-1) receptor agonists and circadian biology. A structured literature search was conducted in PubMed using combinations of the terms 'GLP-1,' 'circadian,' 'chronobiology,' 'sleep,' 'obesity,' and 'type 2 diabetes' through January 2026. Accumulating evidence indicates that GLP-1 physiology is closely coupled to circadian timing systems and sleep-wake regulation. In this narrative review, we synthesize emerging data that reframe GLP-1RAs as chronometabolic modulators, acting at the intersection of metabolism, circadian biology, and sleep. We review circadian control of GLP-1 secretion by intestinal L-cells, emphasizing the role of core clock genes and the vulnerability of incretin rhythms to circadian misalignment from shift work, nocturnal light exposure, and sleep loss. We then examine GLP-1 receptor signaling within central and peripheral clock networks, including feedback effects on hypothalamic and hepatic circadian regulation. Emerging data suggest that GLP-1 signaling is under circadian regulation and may, in turn, influence central and peripheral clock systems. Comparative discussion of semaglutide, liraglutide, and tirzepatide highlights agent-specific pharmacokinetics and emerging clinical data linking GLP-1RA therapy to sleep outcomes, particularly obstructive sleep apnea. Finally, we outline translational opportunities for chronotherapy and precision medicine, positioning GLP-1RAs as integrative tools for metabolic and sleep-related disease rather than purely weight-centric therapies. We propose that GLP-1 receptor agonists may function as chronometabolic modulators, with potential implications for personalized chronopharmacological strategies in metabolic disease.

Resistant and Refractory Obesity: The Complexity of Anti-Obesity Therapy Failure.

Michał Nicze, Maciej Borówka, Adrianna Dec +3 more

Pharmacotherapy is a key component of obesity management, yet treatment failure remains a prevalent challenge in clinical practice. Such failure may present as insufficient pharmacological response, early discontinuation, or post-treatment weight regain, underscoring the discrepancy between clinical trial efficacy and real-world outcomes. The effectiveness of anti-obesity medications (AOMs) is influenced by psychiatric comorbidities, including depression, anxiety, and disordered eating patterns, as well as environmental and socioeconomic factors such as limited healthcare access, weight-related stigma, and high medication costs. Individual characteristics, including physical activity, body composition, visceral adiposity, and microbiome profile, further modulate treatment outcomes. Pharmacokinetic and pharmacotherapeutic limitations such as drug-phenotype mismatch, route of administration, suboptimal formulations, and exposure to counterfeit products also compromise efficacy. No less important are genetic and immunological factors, comprising pharmacogenomic variants of both incretin and melanocortin receptors along with antidrug antibodies (ADAs), which may constitute therapy resistance. Concomitant medications and comorbid endocrine disorders can additionally attenuate weight-loss effects. The objective of this review is to characterize the multifactorial nature of resistance and refractoriness to anti-obesity therapy, and the importance of identifying pretreatment predictive factors for recognizing individuals at risk of inadequate or lack of response, thereby enabling personalized management strategies and improving long-term clinical outcomes, particularly in "difficult-to-treat" patients.

Comparative Effectiveness of Liraglutide and Dulaglutide in Heart Failure with Preserved Ejection Fraction: A Propensity Score-Matched Real-World Study.

Ibrahim Khalil, Imran Hossain, Pallab Sarker +6 more

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve outcomes in heart failure with preserved ejection fraction (HFpEF), but no head-to-head study has compared liraglutide and dulaglutide, two widely used GLP-1 RAs; we aimed to address this gap.

The Therapeutic Potential of Glucagon-Like Peptide-1 Receptor Agonists in Psoriasis and Hidradenitis Suppurativa.

Joshua K Morales, Jennifer Keelin, Toan N Vu +6 more

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), commonly prescribed for type 2 diabetes and obesity, have demonstrated potential anti-inflammatory and immunomodulatory effects that may be beneficial in chronic inflammatory skin conditions such as psoriasis and hidradenitis suppurativa (HS). A systematic review of the literature was conducted, focusing on prospective studies, case reports, and systematic reviews that evaluated the impact of GLP-1 RAs on these diseases. In psoriasis, GLP-1 RAs, particularly liraglutide, have been associated with improvements in the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI), especially among patients with T2D. Reported benefits include enhanced glycemic control, weight reduction, and decreased levels of inflammatory markers, suggesting that GLP-1 RAs may modulate immune pathways and proinflammatory cytokine activity involved in the pathogenesis of psoriasis. Similarly, in HS, GLP-1 RAs such as liraglutide and semaglutide have shown promising results, including decreased lesion severity, improved quality of life, and reduced systemic inflammation. Weight loss induced by these agents may also contribute to symptom improvement by reducing mechanical stress in intertriginous areas and mitigating inflammatory responses associated with HS. Although preliminary evidence suggests that GLP-1 RAs may play a role in managing psoriasis and HS through both metabolic and immunologic mechanisms, current data are limited to early-phase studies and case reports. Further large-scale randomized controlled trials, some of which are ongoing, with diverse study populations are necessary to better understand their efficacy, safety, and long-term impact in the treatment of these chronic inflammatory skin conditions.

Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials.

Rodolfo J Galindo, Kimberly A Gudzune, Michelle Look +5 more

Given the common use of weight-inducing (WI) medications, it is crucial to understand the potential association of these medications with the effectiveness of obesity treatments.

Glucagon-like Peptide-1 Receptor Agonists in Liver Transplant Recipients: A Retrospective Cohort Study.

Hesham Sheashaa, Ramzi Ibrahim, Amani Elshaer +14 more

Liver transplant recipients face high risks of cardiometabolic events after transplant, driven by posttransplant weight gain, diabetes, hypertension, as well as immunosuppression-related side effects. Glucagon-like peptide-1 receptor agonists (GLP1RAs) improve metabolic and cardiorenal outcomes in nontransplant populations, but their role in liver transplant recipients remains understudied.