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Integrated Evidence from VigiBase and Clinical Trials: A Comprehensive Pharmacovigilance Analysis of Seven Glucagon-Like Peptide 1 Receptor Agonists (GLP-1 RAs).
Diabetes Ther
Jiaxun Li, Jizhou Liang, Wei Zhang +2 more
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are key therapies for type 2 diabetes and obesity, regulating blood glucose by mimicking endogenous GLP-1. Despite efficacy, GLP-1 RAs are associated with adverse reactions across multiple organ systems. To address the gap in class-wide comparative safety analyses beyond previous studies limited to single drugs or organ systems, this study systematically evaluated adverse events for all approved GLP-1 RAs to identify hidden risks and support clinical decision-making.
Optimal Ablation Strategies for Persistent Atrial Fibrillation With Heart Failure: Three-Year Follow-Up of a Prospective Multicenter Randomized Trial.
Circ Arrhythm Electrophysiol
Kaige Li, Xinhua Wang, Mu Qin +13 more
Catheter ablation has been shown to improve prognosis in patients with heart failure (HF) and atrial fibrillation (AF); however, the optimal ablation strategy remains undefined.
Prognostic Value of Cystatin C Across Ejection Fraction Spectrum in Heart Failure With Normal to Mild Renal Dysfunction Original Investigation.
Clin Cardiol
Lyu Lyu, Juan Xu, Qiang Yang +3 more
Cystatin C (CysC)'s predictive utility for long-term adverse outcomes in heart failure (HF) patients with normal to mild renal insufficiency remains unclear. This study investigates the relationship between CysC and adverse outcomes in HF patients across the whole ejection fraction (EF) spectrum with normal to mild renal insufficiency.
High N-Terminal Pro-B-Type Natriuretic Peptide Levels Are Associated With Lower Physical Function Independent of Sarcopenia in Community-Dwelling Older Adults: The Shizuoka Study.
Geriatr Gerontol Int
Michitaka Kato, Yoshihiro Tanaka, Takuji Adachi +10 more
Higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been shown to be associated with muscle deterioration and lower physical performance among patients with heart failure (HF). The aim of this study was to clarify the relationships between NT-proBNP levels, sarcopenia, and physical function among community-dwelling older adults.
Warning indicators for heart transplantation requirement at the time of hypertrophic cardiomyopathy diagnosis.
Cardiol J
Marc Ramos-Jovani, Ángela López-Sainz, Magí Brufau +12 more
Timely identification of hypertrophic cardiomyopathy (HCM) patients who may require a heart transplant (HT) in the future is crucial. Our study aimed to identify predictive factors associated with the need for HT in HCM patients.
Harnessing Herbal Power: A Systematic Review of Phytopharmaceuticals in Type 2 Diabetes Management.
J Am Nutr Assoc
Kamalika Chattopadhyay, Pankaj Kumar, Ravishankar Ram Mani +3 more
The Type 2 diabetes mellitus (T2DM) is one of the key health crises facing the world, with the prevalence expected to surpass 783 million adults by the year 2045. It causes premature disability, death and enormous social and economic costs. It is believed that the number of diabetes mellitus (DM) may increase to 592 million in 2035. Although there are conventional therapies, they are very expensive and limited. Despite the fact drugs that are produced synthetically are effective in controlling the disease, there are some side effects that are related with their long-term use. Consequently, the role of the traditional medicine such as plant extracts and pharmacological compounds derived out of plants is becoming very popular. The purpose of this review is to bring together the existing research on the effectiveness of herbal medicine in treating T2DM and especially phytochemicals based on in vitro, in vivo and clinical studies.
Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity with or without type 2 diabetes in Japan and Taiwan (REDEFINE 5): a multicentre, randomised, active-controlled, phase 3a trial.
Lancet Diabetes Endocrinol
Toshimasa Yamauchi, Niels-Peter Becker, Christoffer Andersen Hagemann +7 more
The combination of cagrilintide and semaglutide has been shown in global studies to induce reductions in bodyweight. We assessed the efficacy and safety of a fixed-dose combination of cagrilintide 2·4 mg and semaglutide 2·4 mg versus semaglutide 2·4 mg for weight management in an east Asian population.
Associations of Semaglutide With Skeletal Outcomes in People With Obesity, With and Without Type 2 Diabetes: A Target Trial Emulation.
Diabetes Obes Metab
Yu-Nan Huang, Min-Yu Tsou, Pin-Hung Li +6 more
To evaluate the associations between semaglutide initiation and long-term skeletal outcomes in people with obesity, stratified by type 2 diabetes (T2D) status, using target trial emulation.
Quantitative β-Cell Mass Imaging Redefines Disease Staging and Glycemic Control in Type 1 Diabetes.
Diabetes
Kentaro Sakaki, Takaaki Murakami, Hayao Yoshida +7 more
Noninvasive measurement of pancreatic β-cell mass remains an important unmet need in type 1 diabetes because conventional surrogate markers, such as C-peptide, often lack sensitivity in advanced disease. This study evaluated the glucagon-like peptide 1 receptor-targeted positron emission tomography tracer, 18F-labeled exendin-4-based probe conjugated with polyethylene glycol, [18F]FB(ePEG12)12-exendin-4 (18F-exendin-4), to determine its ability to visualize pancreatic β-cell mass. Positron emission tomography/computed tomography performed at 60 and 120 min after tracer injection in individuals with type 1 diabetes was compared with data from healthy control participants. No serious adverse events occurred. Pancreatic uptake was consistently lower in individuals with type 1 diabetes and showed clear separation between individuals with insulin-dependent diabetes and healthy control participants at 120 min. Pancreatic uptake at 120 min correlated with fasting C-peptide index and inversely with hemoglobin A1c and daily insulin dose per body weight. These findings support [18F]FB(ePEG12)12-exendin-4 positron emission tomography/computed tomography as a noninvasive approach for assessing β-cell mass and disease status.
Evaluating sotatercept in the treatment of pulmonary arterial hypertension.
Future Cardiol
William Salibe-Filho, Nathalia Zorze Rossetto, Luiza Sarmento Tatagiba +5 more
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remodeling, right ventricular overload, and premature death. Despite advances achieved through endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclin analogs, these agents primarily act as vasodilators and do not reverse underlying vascular pathology. Sotatercept, a first-in-class activin signaling modulator, restores the balance between pro- and antiproliferative signaling within the pulmonary vasculature via the TGF-β/activin-BMPR2 pathway, offering a novel disease-modifying mechanism. Following encouraging preclinical data, a series of clinical trials, PULSAR, SPECTRA, STELLAR, ZENITH, and HYPERION, demonstrated consistent efficacy across diverse PAH populations. Sotatercept significantly reduced pulmonary vascular resistance, improved exercise capacity, and decreased morbidity and mortality, including in patients receiving maximal background therapy. Across studies, adverse events were generally mild to moderate, with epistaxis, telangiectasia, and increased hemoglobin being the most common treatment-related events. Collectively, these findings establish sotatercept as a major advance in PAH therapy, marking a transition from purely vasodilatory approaches toward targeted modulation of vascular remodeling. By improving pulmonary hemodynamics and right ventricular function, sotatercept represents a new therapeutic option for improving clinical outcomes across different stages of PAH.
Targeting Drug-Resistant Tuberculosis with Antimicrobial Peptides: Opportunities and Challenges.
Curr Protein Pept Sci
Asad Ahmad, Rufaida Wasim, Anas Islam +1 more
One of the main causes of infectious disease-related deaths globally is Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB). Novel treatment strategies are now much more urgent due to the emergence of Extensively Drug-Resistant (XDR) and multidrug-resistant (MDR) strains. The purpose of this study is to investigate the potential of antimicrobial peptides (AMPs) as TB adjunctive therapeutic agents, with an emphasis on their immunomodulatory and direct antimycobacterial effects.
Metabolic and Bariatric Surgery vs Glucagon-like peptide-1 Receptor Agonist Therapy: A Head-to-Head Comparison in Improvement of Cardiometabolic Risk Profiles.
Ann Surg
Wissam Ghusn, Robert A Vierkant, Noura Jawhar +11 more
To compare 1-year changes in estimated 10-year and lifetime atherosclerotic cardiovascular disease (ASCVD) risk following metabolic and bariatric surgery (MBS) versus glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy among adults with obesity.
Evaluating the Efficacy, Safety, and Practical Considerations of Semaglutide for Weight Loss in Non-Diabetic Adults: A Narrative Review.
Health Sci Rep
Ayesha Laraib, Uswa Ahmad, Syeda Iman Laraib +4 more
The rising global prevalence of obesity has catalyzed the development of potent glucagon-like peptide-1 (GLP-1) receptor agonists. This narrative review evaluates the efficacy, safety, and practical considerations of injectable semaglutide for weight management, specifically in non-diabetic adults, a population where weight loss outcomes often differ from those seen in diabetic cohorts.
Metabolic advances in 2025: from clinical breakthroughs to molecular reprogramming.
Metabol Open
Maria Dalamaga, Junli Liu
The year 2025 represented a turning point in metabolic research, marked by advances that combined unprecedented clinical efficacy with deep mechanistic insight. Landmark obesity trials redefined therapeutic expectations, with head-to-head and combination studies showing that the depth and distribution of weight loss are critical determinants of metabolic benefit across obesity and type 2 diabetes. In parallel, gene-editing studies crossed a translational threshold, showing that durable modification of metabolic pathways in humans is feasible, from bespoke correction of inborn errors to population-scale lipid lowering. Mechanistic investigations challenged long-standing assumptions about metabolic regulation. Experimental work revealed that mitochondrial electron transport functions as a dynamic redox regulator rather than a passive energy conduit, linking coenzyme Q imbalance and reverse electron transport to hepatic steatosis and metabolic dysfunction. Other studies reframed nutrient exposure and endogenous metabolites, demonstrating that non-nutritive sweeteners and cyanide exert context-dependent metabolic effects through regulated endocrine and redox pathways. At the systems level, multi-omics analyses defined reproducible microbiome-metabolome signatures associated with impaired glucose regulation, while artificial intelligence and continuous glucose monitoring exposed dynamic glycemic phenotypes invisible to conventional biomarkers. Precision-nutrition studies further showed that selective manipulation of sulfur amino acid availability can program thermogenic and metabolic responses. Collectively, these studies illustrate how metabolism in 2025 was approached as a modifiable, programmable system, shaped by clinical intervention, molecular control, and data-driven phenotyping, and point toward an era of increasingly precise and integrated metabolic medicine.
Shifts in body mass index category with tirzepatide and associated changes in cardiometabolic risk factors in people with obesity: a post hoc analysis from the SURMOUNT-1 and SURMOUNT-4 trials.
Am J Prev Cardiol
Naveed Sattar, Clare J Lee, Reshmi Srinath +6 more
Obesity is a chronic disease that results in increased morbidity and mortality if left untreated. Tirzepatide is a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist approved in the United States for the treatment of type 2 diabetes, obesity, and obstructive sleep apnea. These post hoc analyses assessed the cardiometabolic risk factors of participants with obesity or overweight treated with tirzepatide who shifted to a lower body mass index (BMI) category.
Tirzepatide as Adjunct to Insulin in Adults With Type 1 Diabetes and Overweight or Obesity: A Systematic Review of Randomized and Real-World Evidence.
Endocrinol Diabetes Metab
Giuseppina Alessia Acucella, Danilo Caponio
Overweight and obesity are increasingly common in adults with type 1 diabetes (T1D), contributing to insulin resistance, higher insulin requirements, and greater cardiometabolic burden. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has shown major metabolic benefits in type 2 diabetes and obesity, but its role in T1D remains unclear. This systematic review evaluated tirzepatide as adjunctive therapy to insulin in adults with T1D and overweight or obesity.
New Horizons in Metabolic Health: Unveiling the Future of Drug Discovery and Development.
Endocr Metab Immune Disord Drug Targets
Jinshan Zhao, Quanyu Qiu, Jidong Zhang +1 more
Metabolic diseases (diabetes, obesity, NAFLD) pose a severe threat to global health, demanding innovative drug solutions.
Aging disrupts the temporal organization of slow oscillations beyond density reduction.
PNAS Nexus
Lucila Capurro, Michael Radloff, María C González +4 more
Macroscopic and rhythmic brain oscillations have recently been shown to play a crucial role in glymphatic function by promoting cerebrospinal fluid flow and facilitating the clearance of metabolic waste. While age-related reductions in the number and amplitude of slow oscillations (SOs; 0.5-1 Hz) are well documented and associated with impaired clearance, little is known about how aging affects the temporal structure of these oscillations. Here, we propose that the rhythmic dynamics with which SOs occur represent a critical, yet overlooked, feature supporting glymphatic function. We introduce a novel classification of SOs based on their temporal organization, distinguishing isolated SOs from trains of consecutive oscillations according to inter-SO intervals. Using overnight electroencephalographic recordings from 57 young and 51 elderly adults across three independent datasets, we compared the proportions of isolated and consecutive SOs as well as the distribution of train lengths. Elderly adults displayed a significantly higher proportion of isolated SOs and shorter oscillatory trains than young adults, even after controlling for SO density and stage composition. Temporal shuffling procedures and analyses of density-matched epochs further supported that these differences cannot be attributed solely to density but instead reflect a genuine age-related loss of rhythmicity. These findings reveal that natural aging not only reduces the amount and amplitude of SOs but also disrupts their temporal regularity. This alteration may weaken the sustained ionic currents that drive cerebrospinal fluid flow, compromise the efficiency of metabolic clearance during sleep, and thereby contribute to increased vulnerability to age-related neurodegenerative processes.
State-of-the-Art Strategies in Heart Failure Screening.
Curr Cardiol Rev
Mahmoud M Ramadan, Abdelrahman Nouh, Hamza Haj-Mohamed +5 more
Heart Failure (HF) is a major global health concern affecting approximately 64 million individuals. Because early asymptomatic stages are frequently overlooked, many patients are diagnosed late, after preventable morbidity and hospitalization. Screening that identifies high-risk individuals earlier may enable timely intervention and disease modification.
Metoprolol-spironolactone combination for coronary heart disease with concurrent heart failure: impact on cardiac function.
Am J Transl Res
Shujun Zhao, Jiwei Zhang, Yansha Zhao
This study intended to clarify the role of metoprolol-spironolactone combination in treating coronary heart disease (CHD) with concurrent heart failure (HF), focusing on its impact on cardiac function.