The living record of
peptide science.

Damage-induced i-loops generate eccDNA from repetitive elements.

Mol Cell

Elia Zanella, Michele Giannattasio, Sara Bisi +2 more

Extrachromosomal circular DNA (eccDNA) drives genome instability and tumorigenesis, warranting thorough investigations of its biogenesis. Here, we report a mechanism of eccDNA formation in human cells, distinct from the one mediated by joining of broken DNA ends. We show that repeats such as telomeres and centromeric alpha satellite form internal loops (i-loops) as a consequence of single-stranded DNA (ssDNA) breaks or gaps rather than double-stranded breaks (DSBs). I-loops are precursors for the excision of eccDNA, visible by electron microscopy (EM) and detectable via rolling-circle amplification. Apoptosis triggers the formation of i-loops and eccDNA at telomeric and alpha satellite repeats. Nanopore sequencing revealed other repetitive elements, including rDNA and retrotransposons, as sources of eccDNA in apoptosis. Based on the prevalence of SSBs over DSBs and the abundance of repeats in the human genome, we propose that the i-loop mechanism contributes substantially to all forms of eccDNA, with implications for tumor biology and genome evolution.

Uncovering immune dysfunction in ACLF: cellular mechanisms, molecular pathways, and therapeutic frontiers.

J Hepatol

Marti Ortega-Ribera, Robert Brenig, Christine Bernsmeier +1 more

Acute-on-chronic liver failure (ACLF) is a life-threatening condition characterized by acute hepatic decompensation, multi-organ failure, and high short-term mortality in patients with liver cirrhosis. A hallmark of ACLF is profound deterioration of the immune system, which contributes to organ-specific excessive inflammation and immune dysfunction, predisposing patients to infection and multi-organ failure. This review aims to elucidate the cellular and molecular mechanisms underlying systemic immune dysfunction in ACLF, highlighting key pathophysiological pathways and their clinical significance. We provide an overview of ACLF including its global prevalence and clinical significance, against the background of the underlying immune dysfunction in its pathogenesis. The discussion focuses on innate immune alterations, such as impaired neutrophil and monocyte phagocytosis, excessive neutrophil extracellular trap (NET) formation, and monocyte/macrophage dysfunction contributing to immuneparesis and exaggerated inflammation, respectively, which evolve in an organ-specific manner. Dysregulation of natural killer (NK) cell cytotoxicity and adaptive immune dysfunction, including changes in T cell subpopulations and B cell antibody production in ACLF, are discussed. We further dissect the emerging evidence of molecular pathways driving dysfunction of immune cells and their impaired ability to control infections in ACLF, emphasizing the roles of pathogen- and damage-associated molecular patterns (PAMPs/DAMPs), toll-like receptor (TLR) signaling, oxidative stress, mitochondrial dysfunction, epigenetic/metabolic reprogramming and immune checkpoint molecules. The review expands on immune cell communication within the immune system (innate and adaptive), with other non-parenchymal and parenchymal cells and at the inter-organ level, detailing interactions between immune cells of key organs and compartments affected during ACLF, including the liver, circulation, brain, gut and kidney. Finally, we summarize the latest preclinical and clinical findings exploring biomarkers of immune dysfunction and immunomodulatory therapeutic strategies aimed at restoring immune homeostasis in patients with ACLF.

Nanocomposite LL37-gold nanoparticles with puerarin for periodontitis-linked atherosclerosis.

J Nanobiotechnology

Yingle Wu, Yanyu Wang, Yanhui Han +4 more

Periodontitis has been increasingly recognized as a contributor to systemic diseases such as atherosclerosis due to its persistent inflammatory nature. The present study evaluates an innovative nanocomposite, LL37-AuNPs@PUE, composed of gold nanoparticles functionalized with the antimicrobial peptide LL37 and puerarin, designed to target vascular inflammation and lipid dysregulation induced by Porphyromonas gingivalis (Pg). The findings show that the nanocomposite effectively reduces bacterial adhesion, attenuates inflammatory responses, and restores lipid metabolic balance in endothelial cells in both in vitro and in vivo models. Overall, LL37-AuNPs@PUE, as a proof-of-concept dual-functional nanotherapeutic platform, provides a new conceptual framework and experimental basis for the treatment of periodontitis and the prevention and therapy of related atherosclerosis. It also lays the groundwork for an integrated oral-systemic therapeutic strategy.

An Ionic Liquid-Based Enteric Formulation for Enhanced Oral Delivery of Semaglutide in Type 2 Diabetes Mellitus.

ACS Appl Mater Interfaces

Juan Tao, Xinrui Lu, Yuning Wei +3 more

Oral delivery of peptide therapeutics remains challenging due to gastrointestinal degradation, poor epithelial permeability, and extremely low bioavailability. To address these limitations, we developed an enteric solid formulation based on sorbic acid-choline ionic liquids (ILs) for the oral delivery of semaglutide (Sema), a glucagon-like peptide-1 (GLP-1) analogue. The IL-based enteric system was designed to enhance peptide stability, reduce gastric degradation, and promote intestinal absorption. In vitro studies demonstrated strong resistance to acidic conditions and pH-responsive release in simulated intestinal fluid. In vivo imaging further revealed prolonged intestinal retention of the IL-loaded enteric particles. Pharmacokinetic evaluation showed a 2.3-fold increase in maximum plasma concentration compared to the reference Rybelsus. In type 2 diabetes mellitus (T2DM) mice, the formulation achieved glucose-lowering efficacy comparable to subcutaneous Sema administration, with additional improvements in hepatic histology. Importantly, repeated-dose studies indicated favorable systemic and gastrointestinal tolerability under the tested conditions. Collectively, these results demonstrate that IL-based enteric formulation enhances oral peptide exposure while maintaining safety, offering a promising strategy for noninvasive T2DM management.

Targeting Meningeal Lymphatic Vessels to Advance Stroke Therapy.

Aging Dis

Yang Liu, Xiansheng Liu, Shihao Lin +7 more

Meningeal lymphatic vessels (mLVs) have recently emerged as pivotal regulators of central nervous system homeostasis, orchestrating cerebrospinal fluid (CSF) drainage, metabolic waste clearance, and neuroimmune surveillance at the brain and meningeal interface. Stroke, ischemic or hemorrhagic, exerts profound functional insults on mLVs, disrupting clearance pathways. These disturbances not only exacerbate acute edema and neuroinflammation but also dictate long-term outcomes, including post-stroke cognitive decline. In this review, we synthesize current understanding of mLVs anatomy and physiology, emphasizing their dynamic remodeling after stroke. We further examine the context-dependent immune functions of mLVs, and their role in shaping post-stroke brain injury and repair. In addition, we discuss emerging therapeutic strategies targeting the glymphatic-lymphatic axis and outline key translational challenges. Although these findings support a framework in which impaired fluid clearance contributes to stroke pathophysiology, most mechanistic insights derive from preclinical models, and direct evidence in human stroke remains limited. Accordingly, therapeutic implications should be interpreted with caution and require rigorous clinical validation.

Aging-Associated CCL8+ Senescent Macrophages Recruit CCR1+ Neutrophils to Promote NETs Formation and Impair Meningeal Lymphatic Drainage.

Aging Dis

Ye Yuan, Ruoli Wang, Qiuguang He +11 more

Meningeal lymphatic vessels (mLVs) are essential for central nervous system (CNS) waste clearance and brain homeostasis, yet their functional decline during aging remains poorly understood. Here, through integrated single-cell and bulk transcriptomic analyses, we identify a distinct macrophage subset characterized by high CCL8 expression (CCL8⁺ macrophages) that accumulates in aged meninges and exhibits a pronounced senescence-associated secretory phenotype (SASP). Trajectory analysis positions CCL8⁺ macrophages at a senescence-associated terminal differentiation state. Mechanistically, CCL8⁺ macrophages engage in pro-inflammatory crosstalk with neutrophils via the CCL8-CCR1 axis, promoting aberrant neutrophil recruitment and excessive neutrophil extracellular traps (NETs) formation within meningeal lymphatic niches. These NETs structurally and functionally impair meningeal lymphatic drainage. Importantly, pharmacological inhibition of CCR1 with BX471 or enzymatic degradation of NETs with DNase I restores meningeal lymphatic function and ameliorates spatial learning and memory deficits in aged mice. Notably, CCR1 antagonist BX471 has previously been evaluated in early human clinical trials and shown favorable tolerability, supporting the translational feasibility of targeting this pathway. In addition, machine learning approaches identify a robust predictive gene signature associated with this senescent macrophage phenotype. Collectively, our findings reveal a previously unrecognized macrophage-neutrophil-NETs axis that links meningeal immunosenescence to meningeal lymphatic dysfunction and cognitive decline and may represent a promising therapeutic target for aging-related neurodegenerative disorders.

Kynurenine-AhR-SLC39A10-Zn2+ signaling reprograms macrophages and enhances pirfenidone efficacy in pulmonary fibrosis.

Cell Commun Signal

Huihui Yue, Ruihan Dong, Jianhan He +13 more

Pulmonary fibrosis (PF) is an irreversible and lethal lung disease characterized by progressive scarring lacking safe and effective treatment options. Recent studies have underscored the role of macrophage polarization in fibrotic progression, yet the role of kynurenine (Kyn), a metabolite of tryptophan (Trp), in macrophages during PF progression remains elusive.

Glucagon-like peptide-1 mimotopes screened from an Fv-antibody library.

J Mater Chem B

Hyung Eun Bae, Dayoung Choi, Jeong Soo Sung +5 more

Glucagon-like peptide-1 receptor (GLP-1R) agonists treat type 2 diabetes and obesity by promoting insulin secretion and suppressing glucagon release. In this study, GLP-1 mimotopes with GLP-1R agonist activity were screened from the Fv-antibody library. The Fv-antibodies represented the hypervariable region of heavy-chain IgG, which included three CDRs and four FRs, and the library was produced by randomizing the CDR3 region with 11 amino acids through site-directed mutagenesis. The GLP-1 mimotopes with GLP-1R agonist activity were screened using monoclonal anti-GLP-1 antibodies and were synthesized into peptides and expressed as Fv-antibodies co-expressed with GFP. The binding affinity of GLP-1 mimotopes was analyzed using a surface plasmon resonance biosensor, and the activity of the GLP-1 mimotopes (expressed Fv-antibodies and synthesized peptides) was analyzed by measuring cyclic adenosine monophosphate (cAMP) production and hormone secretion in pancreatic α- and β-cells. The molecular docking simulations revealed that GLP-1 mimotopes interacted with GLP-1R by targeting key residues known to bind GLP-1, supporting their potential as functional receptor agonists. The effect on fatty acid accumulation was analyzed using hepatocyte cell lines (HepG2 and Huh7), and transcriptomic changes were analyzed by RNA sequencing. In addition, GLP-1R downstream signaling in β-cells was evaluated by western blot analysis of AKT and ERK1/2 phosphorylation. This approach offers a novel strategy to generate new GLP-1R agonists and expand molecular diversity for GLP-1R-targeted therapeutic design.

Gut-Derived GLP-1 Released by Rare Sugar d-Allulose Cooperates With Insulin to Activate Left-Sided Vagal Afferents and Enhance Insulin Sensitivity.

Diabetes

Kento Ohbayashi, Mamoru Tanida, Chikara Abe +6 more

Compared with glucagon-like peptide 1 (GLP-1) receptor agonists, the physiological roles and mechanisms of endogenous, short-lived GLP-1 in glucose metabolism remain poorly understood. We used the rare sugar d-allulose, a noncaloric GLP-1 secretagogue, as a tool to elucidate the physiological actions of endogenous GLP-1. d-allulose-induced intestinal GLP-1 release cooperates with insulin to activate left-side vagal afferents, enhancing insulin action rather than insulin secretion and thereby regulating glycemic control. Because this acute mechanism improved hyperglycemia in type 2 diabetes to an extent comparable to that observed with GLP-1 receptor agonists, targeting GLP-1/insulin-vagal signaling may inform novel therapies and dietary or nutritional interventions for type 2 diabetes.

Expert meeting report: epidemiology and management of acquired hypothalamic obesity.

Front Endocrinol (Lausanne)

Hermann L Müller, Ute K Bartels, Christian Denzer +7 more

Acquired hypothalamic obesity (aHO) is a disease characterized by rapid, clinically significant, and persistent weight gain resulting from damage to hypothalamic structures. aHO is associated with substantial morbidity, increased mortality, and marked impairment in quality of life. Etiologies include craniopharyngioma and other space-occupying lesions of the sellar/parasellar region, neurosurgical procedures, cranial irradiation, and traumatic brain injury. A multidisciplinary panel comprising ten specialists in neuroendocrinology, neurooncology, and neurosurgery from Germany, Austria, and Switzerland convened in Frankfurt am Main, Germany, on November 10, 2025, to discuss contemporary challenges and advances in this field. aHO should be conceptualized and treated within the broader clinical entity of hypothalamic syndrome, a complex disorder involving multiple neuroendocrine deficiencies, disturbances of circadian regulation, impaired control of hunger, satiety, and thirst, altered thermoregulation, and a range of cognitive, sleep-related, and psychosocial dysfunctions. Long-term outcomes for affected individuals are frequently unfavorable, largely due to increased risks of metabolic syndrome, cardiovascular disease, profound reductions in health-related quality of life, and elevated rates of premature mortality. The management of hypothalamic syndrome remains particularly challenging. Pharmacological strategies, including dextroamphetamine and glucagon-like peptide-1 receptor agonists, have demonstrated potential benefits for weight and hyperphagia-related outcomes. Recently, preliminary findings from a prospective, randomized, placebo-controlled clinical trial (TRANSCEND) provided encouraging evidence for the efficacy of setmelanotide, a melanocortin-4 receptor agonist. This perspectives report reviews clinical advances in epidemiology, diagnostics, treatment, and follow-up of patients with aHO and outlines key directions for future research aimed at improving outcomes in this vulnerable population.

Unmasking Adrenal Insufficiency in COVID-19: The Diagnostic Challenge of Concomitant Acute Kidney Injury and High Ileostomy Output.

Am J Case Rep

Ioanna I Yglesias Dimadi, Afshan Hussain, Bronson Benno Joseph Raja

BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has elucidated various extrapulmonary manifestations of severe acute respiratory syndrome coronavirus 2, including endocrine complications that affect the hypothalamic-pituitary-adrenal axis. Efforts to diagnose adrenal insufficiency in critically ill patients are challenging due to overlapping symptoms such as hypotension and fatigue. This challenge is amplified in patients with renal comorbidities, among whom classic electrolyte derangements of adrenal insufficiency (eg, hyperkalemia) may be masked by acute kidney injury (AKI) and renal replacement therapy. CASE REPORT A 46-year-old man with chronic kidney disease and an ileostomy presented with fatigue, abdominal pain, high ileostomy output, and hypotension. Evaluation revealed COVID-19 with concomitant AKI, metabolic acidosis, and hyperkalemia. Initial management via hemodialysis and remdesivir corrected the acidosis and electrolyte abnormalities. However, after renal recovery and discontinuation of dialysis, the patient developed recurrent, refractory hypotension, hyperkalemia, and hypoglycemia, prompting assessment for adrenal dysfunction. Morning cortisol levels were critically low. A subsequent cosyntropin stimulation test showed a blunted cortisol response, confirming adrenal insufficiency. Hydrocortisone and fludrocortisone treatments resulted in hemodynamic stabilization and resolution of the electrolyte abnormalities. CONCLUSIONS This case highlights the "masking" effect of dialysis on the clinical presentation of adrenal insufficiency. Clinicians must maintain a high index of suspicion for adrenal insufficiency in patients with COVID-19 who display recurrent hypotension or hyperkalemia despite renal recovery. Furthermore, the presence of hyperkalemia in a patient with high ileostomy output is paradoxical and should prompt immediate evaluation for mineralocorticoid deficiency.

Assessment of Carbon Emission Impact of Semaglutide in Patients with Type 2 Diabetes in the United Kingdom using an Innovative Modelling Approach.

Value Health

Niels Lund, Andreas Rasche, Matthew Taylor +5 more

To evaluate the carbon footprint and clinical outcomes of once-weekly subcutaneous semaglutide in patients with type 2 diabetes mellitus (T2DM) in the United Kingdom.

Data-driven prioritization of high-risk individuals for weight loss interventions.

Nat Med

Kamil Demircan, Julia Carrasco-Zanini, Alice Williamson +13 more

New obesity medications have demonstrated efficacy in trials, but their real-world deployment is partly limited by the absence of approaches that identify individuals for treatment based on risks for obesity-related complications. Here we present a risk prediction model to guide prioritization of high-risk individuals. In a population-based sample of ~200,000 individuals with a body mass index (BMI) exceeding 27 kg m-2, our machine learning framework identified the 20 most informative features, from among thousands tested, that predict future onset of 18 complications of obesity, providing information beyond BMI. An integrated model (OBSCORE) successfully stratified individuals into risk groups based on incidence over 10 years: for example, 5.7%, 1.8%, 0.9%, 0.4% and 0.1% for cardiovascular mortality. We demonstrate generalizability of the model in independent populations of European and non-European ancestry and, in SURMOUNT-1 trial participants, show that weight loss was similar across baseline OBSCORE risk groups and that predicted risks decreased following treatment with tirzepatide. In summary, OBSCORE provides a framework for prioritizing high-risk individuals with overweight or obesity based on their risk of obesity-related complications, complementing BMI-based frameworks.

Wired for immunity: neuroimmune control of the lung by sensory neurons.

Nat Rev Neurosci

Anna M Ehlers, Idaira M Guerrero-Fonseca, Christophe Altier +2 more

Respiratory diseases, including bacterial pneumonia, viral infections and allergic asthma, are leading causes of hospitalization, yet current therapies often fall short. The lower airways are densely innervated by pain-transmitting sensory neurons (nociceptors) that arise from the nodose-jugular ganglia of the vagus nerve, with additional contributions from the spinal dorsal root ganglia. Converging evidence indicates that reciprocal neuroimmune signalling between lung-innervating sensory neurons and immune cells lies at the centre of pulmonary defence, inflammation and tissue repair. Among several immunomodulatory neuropeptides, calcitonin gene-related peptide (CGRP), released by activated TRPV1-positive nociceptors, has context-dependent functions. CGRP supports tissue protection and repair by shaping macrophage and neutrophil activation states, yet these same actions can exacerbate pathology during bacterial infection. In allergic asthma, pulmonary neuroendocrine cells act as early epithelial sentinels that amplify type 2 immunity and help to define state-dependent effects of CGRP as well as other neuropeptides, including vasoactive intestinal peptide (VIP), neuromedin U (NMU) and substance P (SP). An updated framework that accounts for phase-specific and context-specific neuromodulation could enable new therapeutic strategies, including targeted inhibition or modulation of defined pathways to preserve essential reflexes while meaningfully altering disease trajectories and outcomes. Incorporating the neural state and exposure history will be critical for developing disease-modifying therapies informed by pulmonary neuroimmunology.

Mechanobiological landscape of muscle stem cells.

Skelet Muscle

Kotaro Hirano, Yuji Hara

γ-Aminobutyric acid enhances myogenesis and heat/cold stress resistance in bovine muscle satellite cells.

Front Vet Sci

Abid Manzoor, Sajida Naseem, Zhiqi Fu +5 more

γ-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the central nervous system and is involved in the development of neural tissue as well as the regulation of its functions. Meanwhile, GABA has also been demonstrated to confer multiple physiological benefits, including alleviating stress and improving metabolic homeostasis. This study investigated GABA effects on proliferation, differentiation, and temperature stress protection of bovine skeletal muscle satellite cells (BSCs).

Cardiometabolic and Renal Outcomes in Semaglutide Users with Type 2 Diabetes Achieving Glycemic and Weight Goals: An Observational Cohort Study.

Adv Ther

Xi Tan, Wan-Lun Tsai, Yuanjie Liang +4 more

Within the cardiovascular-kidney-metabolic syndrome (CKM) framework, semaglutide has demonstrated benefits beyond glycemic control and weight loss in clinical trials. However, most real-world studies in type 2 diabetes (T2D) have limited assessment of broader cardiometabolic and renal outcomes. We evaluated CKM-relevant outcomes among individuals with T2D who achieved substantial hemoglobin A1c (HbA1c) and weight improvements after initiating semaglutide in real-world settings.

Semaglutide in obesity and type 2 diabetes: A review of clinical trial evidence from 1 to 5 semaglutide treatment effect in people with obesity program.

Indian J Pharmacol

Aastha Khanna, Vipin Kumar, Sahil Gola

Obesity and type 2 diabetes mellitus (T2DM) are widespread health concerns that often coexist, contributing to increased cardiometabolic risks and premature death. Despite advancements in both lifestyle interventions and medical treatments, achieving lasting weight reduction and stable glycemic control remains a major clinical challenge. This review examines findings from the semaglutide treatment effect in people with obesity 1 (STEP) 1-5 trials, which assessed the effectiveness, safety, and long-term outcomes of once-weekly semaglutide 2.4 mg for weight management in adults. These trials included individuals with and without T2DM, enabling comparison across different populations and interventions. In nondiabetic participants (STEP 1, 3, and 4), semaglutide led to average weight reductions between 10% and 17%, while in patients with T2DM (STEP 2), the reduction was around 10%. The inclusion of intensive behavioral therapy in STEP 3 further enhanced weight loss outcomes. Results from STEP 4 highlighted notable weight regain following treatment withdrawal, reflecting the relapsing nature of obesity. STEP 5 confirmed semaglutide's ability to maintain significant weight loss (~15%) and improve metabolic health over a 2-year period. The most common side effects were gastrointestinal in nature but were generally manageable and nonsevere. Collectively, these trials support semaglutide 2.4 mg as an effective and sustainable option for managing obesity and overweight, including in people with T2DM. The data also emphasize the importance of combining pharmacological therapy with lifestyle modifications and recognize obesity as a long-term condition that necessitates continuous treatment.

Weight loss maintenance after tirzepatide cessation in people with overweight/obesity: a real-world follow-up of the phase 3 SURMOUNT-CN trial.

Life Metab

Congling Chen, Zhen Ying, Qi Tang +11 more

Tirzepatide, a dual GIP/GLP-1 receptor agonist, has shown unprecedented efficacy in weight loss and improving metabolic parameters in clinical trials. However, the durability of these benefits after treatment cessation remains poorly understood. This study aimed to investigate the effect of tirzepatide cessation on body weight change in people with obesity or overweight. This real-world, observational 26-week follow-up study included participants who completed 52 weeks' study treatment during SURMOUNT-CN (NCT05024032). The analysis excluded participants who received anti-obesity medications or bariatric procedures during the 26-week follow-up. Key outcomes were the changes in body weight and waist circumference after 26 weeks, from treatment cessation (Week 52) and trial baseline (Week 0), by the SURMOUNT-CN treatment groups (tirzepatide 10 or 15 mg, or placebo). Overall, 152 participants were included (tirzepatide 10 mg: n = 57; tirzepatide 15 mg: n = 51; placebo: n = 44). Following treatment cessation (Week 52), the mean (SD) percentage changes in body weight at Week 78 were 9.1% (7.4), 12.3% (9.9), and 1.8% (5.2), and the absolute changes in waist circumference were 2.9 cm (7.5), 5.5 cm (6.5) and -0.5 cm (5.6), in tirzepatide 10 and 15 mg, and placebo groups, respectively. From trial baseline to Week 78, the mean (SD) net percentage weight changes were -8.7% (6.9), -10.6% (10.2), and -2.5% (7.0), and the changes in waist circumference were -10.5 cm (8.1), -10.6 cm (9.3) and -4.0 cm (7.2), in the tirzepatide 10 and 15 mg, and placebo groups, respectively. At Week 78, residual improvements in multiple cardiometabolic indicators were evident in the tirzepatide groups. Despite weight gain following tirzepatide cessation, participants achieved a large net weight loss and reduction in waist circumference from trial baseline to Week 78, with residual improvements in several cardiometabolic indicators.

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

Mol Cell Biochem

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.