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Tirzepatide.
Ceska Slov Farm
Jan Brož, Marika Koželuhová, Juraj Michalec +1 more
Tirzepatide represents a significant breakthrough in the treatment of type 2 diabetes mellitus and/or obesity as the first dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. Current analysis of available clinical data demonstrates the exceptional efficacy of tirzepatide in glycemic control, with a dose- and duration-dependent reduction in HbA1c of 20.4-28.2 mmol/mol. Weight reduction reaches 5-20.9 % with 72 weeks of therapy, with the effect being dose-dependent. The mechanism of action includes improved insulin sensitivity, delayed gastric emptying, and modulation of central regulatory centers for food intake. The safety profile is characterized primarily by gastrointestinal side effects with a treatment discontinuation rate of 4-10 %. Tirzepatide also has beneficial effects on cardiovascular risk factors, including lipid profile and anti-inflammatory biomarkers. A key strategy for optimizing therapeutic outcomes is gradual dose escalation and individualization of treatment according to the patient's clinical condition.
Adjunctive use of glucagon-like peptide-1 receptor agonists after bariatric surgery: updated systematic review and meta-analysis of randomized controlled trials.
Acta Diabetol
Sakshi Arora, Fnu Amna, Fatemeh Akbarpoor +6 more
We meta-analyzed randomized trials to assess efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) after bariatric surgery.
Humanin Mitigates Aβ-Induced Retinal Pigment Epithelium Injury via AMPK-Beclin1-Dependent Mitophagy.
Aging Cell
Ha Young Jang, Suyeon Choi, Soo-Jin Kim +5 more
Amyloid beta (Aβ), a key component of drusen in age-related macular degeneration (AMD), induces oxidative stress, mitochondrial dysfunction, and degeneration in the retinal pigment epithelium (RPE), contributing to progressive vision loss in the elderly. We investigated the protective role of Humanin (HN), a mitochondria-derived peptide with known neuroprotective effects in Aβ-related neurodegenerative diseases, in retinal pathology induced by subretinal injection of FITC-labeled Aβ. HN enhanced the clearance of Aβ-accumulated mitochondria in the RPE while preserving retinal function and RPE barrier integrity. In ARPE-19 cells, HN activated AMP-activated protein kinase (AMPK), leading to phosphorylation of ULK1 and Beclin1, which promoted the interaction between Beclin1 and Parkin and their translocation to mitochondria. This process facilitated the removal of Aβ-accumulated mitochondria in the RPE. Our results demonstrate that targeting mitophagy in the RPE with HN may offer a promising therapeutic strategy for AMD.
A nomogram for risk prediction in patients with heart failure and diabetes: Development and validation.
Medicine (Baltimore)
Zhe Zhang, Dengao Li, Jumin Zhao +3 more
Heart failure (HF) commonly coexists with type 2 diabetes mellitus (T2DM), and this combination is linked to a heavier symptom burden and less favorable clinical outcomes. In this retrospective single-center study, a total of 958 consecutive patients were included, among whom 453 had T2DM, with a mean age of 68.23 ± 5.76 years. The diagnosis of HF was confirmed by a multidisciplinary team in accordance with the European Society of Cardiology criteria, and 232 patients were found to have both T2DM and HF. Relative to diabetic patients without HF, those with HF more often presented with dyspnea or fatigue, paroxysmal nocturnal dyspnea/orthopnea, and ankle swelling or nocturia (all P < .001). They also showed higher rates of wheezing/rhonchi (P = .021), fluid and sodium retention (P = .008), ST-T abnormalities (P = .033), abnormal Q-waves (P = .001), and NT-proBNP levels ≥ 15 pmol/L (approximately 125 pg/mL; P < .001). Potential predictors were first selected using least absolute shrinkage and selection operator (LASSO) regression, after which multivariable logistic regression was performed to construct a nomogram for predicting HF risk in patients with T2DM. The multivariable model indicated that ST-T abnormalities, NT-proBNP, ischemic heart disease, and atrial fibrillation were independently related to HF (all P < .05). The nomogram exhibited strong apparent discriminatory ability together with satisfactory calibration, suggesting that NT-proBNP-based risk stratification may be useful for HF screening in individuals with T2DM.
Lactiplantibacillus plantarum KLDS1.0344 ameliorates depressive-like behavior in CUMS mice: integrative multi-omics evidence linking gut microbiota alterations to sphingolipid and glycerophospholipid metabolic pathways.
Food Funct
Fangfei Dou, Yuxing Li, Wenqing Lv +5 more
Depression is a common and debilitating psychiatric disorder, and current pharmacotherapies are often limited by delayed onset, variable efficacy, and adverse side effects. Therefore, safer and more effective adjunctive or alternative strategies are needed. In the present study, a chronic unpredictable mild stress-induced murine model was used to evaluate the antidepressant potential of Lactiplantibacillus plantarum KLDS1.0344 by integrating behavioral assessments, neurochemical analyses, 16S rRNA sequencing, and untargeted metabolomics of intestinal contents. KLDS1.0344 significantly ameliorated depressive-like behaviors in the open field, tail suspension, forced swim, and sucrose preference tests, with the most pronounced effects observed at the high dose. These behavioral improvements were accompanied by reduced HPA-axis hormones (corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone) and partial restoration of monoamine neurotransmitters (dopamine, norepinephrine, and 5-hydroxytryptamine) and brain-derived neurotrophic factor. Multi-omics analyses further showed that high-dose KLDS1.0344 was associated with remodeling of the gut microbiota, particularly the restoration of Lactobacillus and alterations in other key taxa, together with marked changes in sphingolipid- and glycerophospholipid-related metabolic profiles. Correlation analysis suggested coordinated associations between microbial shifts and intestinal lipid metabolic features, supporting a candidate microbiota-metabolite framework related to the psychobiotic effects of KLDS1.0344. Overall, this study provides evidence supporting the psychobiotic potential of KLDS1.0344 and its possible application in functional foods for depression-related intervention.
Hypothalamo-Pituitary Dysfunction and Association with Pituitary Siderosis in Adult Subjects with Transfusion-Dependent Beta-Thalassemia: all Is not Dark.
Indian J Hematol Blood Transfus
Subin Siddiqui, Jayaditya Ghosh, Chirag K Ahuja +9 more
Transfusion-dependent beta-thalassemia (TDT) is frequently associated with endocrine dysfunction secondary to hemosiderosis involving multiple organs. This study aimed to evaluate long-term endocrine dysfunction, neuroradiological manifestations, and biochemical markers of iron overload in adult TDT subjects, alongside analyzing associations between pituitary siderosis and endocrine deficits. A cross-sectional study was conducted on 63 adult TDT subjects treated at a tertiary care center in North India. Patient history, clinical examination, biochemical evaluation, and neuroimaging findings were recorded. Hormonal assessments included insulin-like growth factor-1 (IGF-1), growth hormone (GH), thyroid function, cortisol, adrenocorticotropic hormone, sex steroids, and gonadotropins. Dynamic hormone testing was conducted to assess GH status (n = 44) and adrenal reserve (n = 45). Iron deposition in the brain, liver, and heart was assessed radiologically using MRI. Sixty-three subjects (43 males), median age 27 years (IQR: 22-30), were analyzed. Most (59/63) had thalassemia major (TM); the remainder had thalassemia intermedia (TI). Endocrine deficits included low IGF-1 (75.8%), low DHEAS (73%), hypocortisolism (64.5%), hypogonadism (58%), growth hormone deficiency on provocation test (56%), and central hypothyroidism (24%). MRI revealed pituitary siderosis in 76.6%, hepatic siderosis in 53.4%, and cardiac siderosis in 38.2%. Calvarial thickening and diploic space widening in 81% each were common findings. No significant association was observed between pituitary siderosis, pituitary height, and endocrine deficits. Most TDT subjects experience hypothalamo-pituitary dysfunction despite chelation therapy, emphasizing the need for close monitoring. While MRI is valuable for assessing systemic hemosiderosis, its utility in predicting endocrine dysfunction is limited.
ApoEVs@FeSe2-RGD as a synergistic redox-immune regulator for accelerating wound healing.
J Mater Chem B
Zhen Ma, Minghao Zhou, Juan Tong +6 more
Wound healing still faces many significant challenges, such as excessive oxidative stress, persistent inflammation and disrupted angiogenesis. To overcome these obstacles, we developed a biomimetic hybrid regulatory platform (ApoEVs@FeSe2-RGD) by anchoring redox-active FeSe2 nanorods onto mesenchymal stem cell-derived apoptotic extracellular vesicles (ApoEVs), followed by surface functionalization with cyclic RGD (cRGD) peptides. This regulator effectively synergizes the robust reactive oxygen species (ROS)-scavenging capacity of FeSe2 with the exceptional biocompatibility of cRGD-functionalized ApoEVs. In vitro assessments revealed that ApoEVs@FeSe2-RGD efficiently cleared abnormally produced ROS to recalibrate the oxidative microenvironment. Consequently, it inhibited pro-inflammatory activation while driving macrophage polarization toward an anti-inflammatory phenotype. The reparative cytokines derived from these reprogrammed macrophages significantly enhanced the migration, proliferation, and angiogenic capacity of endothelial cells. Furthermore, the in vivo assessments in a full-thickness wound healing model demonstrated that this vesicle-scaffolded regulator enhanced the wound closure rate and promoted re-epithelialization, collagen deposition, and neovascularization with good biosafety. Mechanistically, transcriptomic profiling combined with protein validation demonstrated that these therapeutic effects were mediated by the suppression of the NF-κB signaling pathway. Collectively, our study demonstrated that ApoEVs@FeSe2-RGD holds potential as a therapeutic strategy for wound healing by restoring redox homeostasis and orchestrating immune-vascularization coupling for high-quality tissue regeneration.
Pulmonary Hypertension and Kidney Disease: A Review of a High-Risk Patient Population.
Cardiol Rev
Yosef Tobi, Steven W Buffer, Gabriel Grullon +6 more
Pulmonary hypertension (PH) is a multifaceted disease driven by increased pulmonary vascular resistance and right ventricular afterload, eventually progressing to right-sided heart failure and a high mortality rate. Kidney dysfunction, a common comorbidity in patients with PH, complicates treatment and impacts prognosis. In this literature review, we seek to broadly explore this coincidence of diseases, primarily focusing on chronic kidney disease (CKD) developing after a primary diagnosis of pulmonary arterial hypertension (PAH). We discuss prevalence, pathophysiologic mechanisms of disease, management of disease including the use of primary PAH therapies in the setting of renal disease, as well as background therapy for kidney disease and PAH comorbidities. This paper further seeks to evaluate associated comorbid conditions such as anemia and iron deficiency. We performed a literature search of several online medical databases, with a primary focus on Pubmed, to explore the findings of multiple systematic reviews and meta-analyses, clinical trials, and preclinical studies using animal models, among others. We found that while there is generally a good amount of consensus data for PH, CKD, and PH in the setting of preexisting CKD, little has been published regarding the specific focus of patients developing kidney dysfunction in the setting of PH.
Fibroblast-derived CCL2 orchestrates immune responses and defends against Staphylococcus aureus skin infection.
Cell Mol Immunol
Tatsuya Dokoshi, Marta Palomo-Irigoyen, Kazuki Dai +11 more
Host defense against invasive bacterial infections of the skin is essential for survival. It involves a complex yet incompletely understood process of microbial recognition followed by innate and adaptive systems for communication between resident and recruited cells to mount an effective defense. Stromal fibroblasts have not been classically considered immunocytes but are gaining recognition for their critical role in inflammation. Here, we identify fibroblast-derived C-C motif chemokine ligand 2 (CCL2) as a key mediator of host defense against invasive Staphylococcus aureus infection. Single-cell RNA sequencing revealed that fibroblasts are a predominant source of CCL2 under steady-state conditions in both human and mouse skin. The use of mice with a conditional deletion of CCL2 in fibroblasts demonstrated that the expression of CCL2 by fibroblasts alters macrophage cytokine production and antigen-presentation-associated responses and is important for monocyte recruitment. Additionally, we revealed a novel role for fibroblast-derived CCL2 in promoting fibroblast-to-adipocyte differentiation via ERK and p38 signaling, leading to reactive adipogenesis and enhanced production of the antimicrobial peptide cathelicidin. In mice with targeted deletion of Ccl2 in fibroblasts, these host immune responses are impaired, and S. aureus infection of the skin is greatly increased. These findings highlight fibroblast-derived CCL2 as a critical regulator of immunity and suggest its broader implications in inflammatory and infectious diseases.
Dual Glucagon and GLP-1 Receptor Agonist Survodutide Improves Biomarkers of Beta-Cell Function and Insulin Sensitivity in People With Type 2 Diabetes or Living With Overweight/Obesity.
Diabetes Obes Metab
Elif I Ekinci, Sandra González Maldonado, Anna Unseld +3 more
This post hoc analysis evaluated the effect of survodutide on beta-cell function, insulin sensitivity, and glucose biomarkers in two phase 2 trial populations.
Rapid and harmonized analytical workflow for the determination of peptidic and non-peptidic doping agents in dried and liquid blood matrices.
Analyst
Monica Mazzarino, Thibo Colpaert, Koen Deventer +1 more
Recently, methods for detecting small peptides in dried blood spots have been published. These procedures typically involve multiple sample preparation steps, resulting in labor-intensive and costly workflows. In the present study, we report a fast, streamlined, and harmonized analytical workflow to detect 54 prohibited peptidic and non-peptidic compounds in dried blood spots, serum, and plasma. Sample preparation is based on a single microextraction step using 500 µL of a methanol/water (8 : 2, v/v) mixture. Detection was performed using liquid chromatography coupled with high-resolution mass spectrometry. The validation results showed satisfactory performance with respect to selectivity (no interferences were detected at the retention times of the analytes), detection limits (0.05-1.25 ng mL-1), carry-over (no signals in the negative sample injected after the positive sample), matrix effect (5-33%), extraction yield (15-80%), and extract stability (the target analytes were stable for at least 72 h in the autosampler at 10 °C). The method was successfully applied to samples containing sub-ng levels of ibutamoren, confirming that the analytical procedure presented in this study is fit for purpose within the doping-control framework. Stability studies showed that all compounds were stable (variation lower than 15%) for at least two months at -20 °C in all the blood matrices considered. At 4 and 22 °C, alexamorelin, AOD9604, buserelin, hGH 176-191, kisspeptin-10 and LHRH were extensively degraded after one week in serum and plasma, whereas BPC-157, TB500, vasopressin, lypressin, and terlipressin showed complete degradation only in serum. In contrast, in dried matrices all compounds remained detectable throughout the entire duration of the study, indicating that samples can be transported and stored under non-refrigerated conditions, thereby reducing costs.
The TRPM7 inhibitor carvacrol suppresses angiogenesis and vasculogenic mimicry in triple-negative breast cancer.
Int J Biol Sci
Tianci Tang, Na Zhao, Moqin Qiu +7 more
Vasculogenic mimicry (VM) contributes significantly to tumor aggressiveness and resistance to anti-angiogenic therapies. Simultaneous inhibition of both angiogenesis and VM represents a promising strategy to improve therapeutic outcomes in aggressive cancers, such as triple-negative breast cancer (TNBC), which responds poorly to anti-angiogenic therapies. In this study, we identified carvacrol, a natural monoterpenoid phenol widely used as a food additive, as a dual inhibitor of angiogenesis and VM in TNBC. Carvacrol preferentially inhibited angiogenesis in endothelial cells (ECs) and VM in TNBC cells at concentrations that had minimal effects on TNBC cell proliferation. Mechanistically, carvacrol directly bound to the vanilloid-like (VL) site of transient receptor potential melastatin 7 (TRPM7), thereby inhibiting channel activity and attenuating Zn2+ influx. This triggered dephosphorylation of the mammalian target of rapamycin (mTOR) and subsequent proteasomal and lysosomal degradation of key receptor tyrosine kinases (RTKs), including vascular endothelial growth factor receptor 2 (VEGFR2), Tie2, fibroblast growth factor receptor 1 (FGFR1), and insulin-like growth factor 1 receptor (IGF1R) in ECs, as well as FGFR1 and IGF1R in TNBC cells. Genetic knockdown of TRPM7 recapitulated the anti-vascular effects and signaling alterations induced by carvacrol. In vivo, carvacrol effectively suppressed TNBC vascularization and growth in a mouse dorsal skinfold chamber model and an orthotopic xenograft model. Together, these findings suggest that carvacrol preferentially targets angiogenesis and VM in TNBC by suppressing the TRPM7/Zn2+/mTOR/RTKs axis, highlighting it as a promising therapeutic candidate for TNBC and potentially other tumors resistant to anti-angiogenic therapies, while positioning the TRPM7 channel as a novel anti-vascular target for TNBC treatment.
Sarcopenia and satellite cell homeostasis disruption: the dual function of NAD+ metabolism.
Front Nutr
Chenyuan Li, Yue Ai, Jieni Yan +1 more
Sarcopenia is an age-related syndrome characterized by progressive loss of skeletal muscle mass and function, which is closely associated with impaired regenerative capacity of muscle satellite cells (MuSCs). During aging, the MuSC niche undergoes severe deterioration, including mitochondrial dysfunction, chronic inflammation, and neuromuscular junction (NMJ) degeneration, all of which compromise MuSC quiescence, proliferation, and differentiation. Nicotinamide adenine dinucleotide (NAD+) serves as a critical coenzyme and signaling molecule that governs MuSC homeostasis in a context-dependent, dual-function manner. Moderate NAD+ repletion via precursors such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR) activates SIRT1 and SIRT3, enhances mitochondrial bioenergetics, reduces oxidative stress, and promotes MuSC proliferation and myogenic differentiation. In contrast, under pathological or aging conditions, excessive or dysregulated NAD+ signaling activates SIRT2 to deacetylate PAX7 and repress Myogenic Differentiation 1 (MyoD), leading to cell-cycle arrest and MuSC exhaustion. This review adopts a hypothesis-driven framework to systematically summarize the molecular crosstalk between NAD+ metabolism, sirtuin family deacetylases (SIRTs), and MuSC fate regulation. We integrate evidence from nearly 60 representative preclinical and clinical studies, clarify the dual-function role of NAD+, and address current inconsistencies in the field. We also highlight key limitations and propose future directions for developing NAD+-targeted therapies for sarcopenia.
Pathogenetic and clinical aspects of fibromyalgia: one year in review 2026.
Clin Exp Rheumatol
Cristina Iannuccelli, Martina Favretti, Benedetta Bianchi +16 more
Fibromyalgia (FM) is a complex chronic pain condition with a multifaceted pathogenesis and heterogeneous clinical presentation. This narrative review summarises the most relevant studies published in 2025 on the pathogenetic and clinical aspects of FM. Central sensitisation remains the main neurobiological mechanism, supported by evidence of increased ascending nociceptive signalling, impaired descending inhibition, network reorganisation and autonomic dysfunction. Emerging findings have also explored a possible role for non-classical autoimmune mechanisms, as patient-derived IgG has been shown to induce pain hypersensitivity and bind dorsal root ganglion neurons and satellite glial cells, suggesting potential interactions between immune and metabolic pathways. The gut microbiome is increasingly implicated, showing reduced diversity, distinct signatures, and transferable pain phenotypes. Genetic studies identify a predominantly neuronal architecture involving 26 loci linked to proteins essential for neuronal function. Oxidative stress remains a major hypothesis, supported by elevated biomarkers and preclinical evidence for mitochondrial-targeted strategies. Early-life stress may selectively affect the right amygdala, contributing to long-term vulnerability. Clinically, pain in FM appears heterogeneous and may not be entirely explained by a purely nociplastic paradigm, as some studies have suggested the presence of neuropathic-like features in at least a subset of patients. Likewise, residual pain in inflammatory arthritis remains a multifactorial and incompletely characterised entity, potentially sharing some mechanisms with FM while also encompassing distinct and broader pathophysiological processes. Cognitive dysfunction (fibrofog) represents a multidimensional clinical construct whose underlying mechanisms remain only partially understood. FM is also associated with high affective burden, systemic symptoms, and reduced muscle performance consistent with dynapenia. Stigma and symptom invisibility continue to negatively affect care, while sex and gender influence disease expression and burden. Digital health and AI offer new opportunities but also raise concerns regarding misinformation. Overall, current evidence supports a multidimensional view of FM and highlights the need for updated diagnostic criteria and more integrated, personalised models of care.
Transcriptomic insights into temperature regulation of proliferation and differentiation in skeletal muscle cells of Nibea albiflora.
Comp Biochem Physiol Part D Genomics Proteomics
Jingru Zhang, Dong Liu, Wenzhi Cheng +8 more
Myogenesis involves sequential stages of muscle satellite cell activation, myoblast proliferation, differentiation, and fusion into multinucleated myotubes. Teleost muscle exhibits indeterminate growth and is highly sensitive to environmental temperature, yet the underlying mechanisms by which temperature regulate proliferation and differentiation remain poorly understood. In this study, we established a primary skeletal muscle cell culture from the yellow drum (Nibea albiflora), an economically important marine fish, and integrated morphological observations with comparative transcriptomics analysis to characterize cellular and molecular responses at 28 °C and 20 °C during both proliferation and differentiation stages. Phenotypic analysis revealed that 28 °C significantly enhanced both myoblast proliferation and myogenic differentiation ability compared with 20 °C. Transcriptomic profiling revealed that at 28 °C, differentiation upregulated extracellular matrix(ECM) organization, calcium signaling, and sarcomere assembly, while proliferation enhanced focal adhesion, growth factor signaling, and lipid metabolism. At 20 °C, differentiation was characterized by glutathione metabolism, and ferroptosis, while proliferation involved cytokine-cytokine receptor interaction and negative regulation of signal transduction. Core myogenic regulatory factors (MRFs), particularly myogenin, were strongly upregulated at 28 °C during the differentiation stage, serving as an internal control. Based on these findings, we propose a testable model that elevated temperature coordinates Ca2+-dependent MRF activation with ECM-integrin signaling to drive sarcomere assembly and muscle growth. Key differentially expressed genes (DEGs) regulating myogenesis in N. albiflora were also identified. This study provides a mechanistic framework for temperature adaptation in teleost skeletal muscle and identifies candidate genes for functional validation and marker-assisted selection, as well as a rationale for temperature management strategies to improve aquaculture yield of N. albiflora.
Vitamin D-AMP axis in host defense against fungal infections.
Front Nutr
Nuraly S Akimbekov, Ilya Digel, Svetlana K Sakhanova +3 more
Vitamin D-mediated regulation of antimicrobial peptides (AMPs) is an important focus in innate immunology and is aimed at elucidating the role of vitamin D in enhancing antimicrobial defense. AMPs are short protein chains that serve as a first line of defense against invading pathogens, including fungi, bacteria and viruses. Unlike conventional antibiotics, AMPs are produced endogenously and are less likely to induce antimicrobial resistance, making them promising candidates for treating infections caused by drug-resistant pathogens. Studies indicate that optimal vitamin D levels are essential for activating antimicrobial pathways and regulating AMPs that target multiple fungal pathogens. This article summarizes recent findings on vitamin D-induced AMPs in the context of invasive fungal infections. It also distinguishes vitamin D as a host immune modulator from vitamin D3 as a putative active antifungal compound, given that direct antifungal use is limited by supraphysiologic dosing requirements, pharmacologic impracticality, and risks of hypercalcemia and hyperphosphatemia, especially in patients with granulomatous diseases. Model limitations and species differences are also discussed, including primate-specific CAMP vitamin D response element regulation, which constrains direct translation of rodent vitamin D-to-LL-37 findings to human fungal disease. Current global fungal priority frameworks and resistance surveillance support emphasizing Candida, Aspergillus, and Cryptococcus in this review of invasive fungal disease and translational host-defense evidence, underscoring the relevance of these pathogens.
Quality of life, morbidity, mortality, and long-term prognosis after craniopharyngioma.
Front Endocrinol (Lausanne)
Hermann L Müller
During the first months following diagnosis and treatment of childhood-onset craniopharyngioma, a substantial proportion of patients experience rapid and marked weight gain. This frequently progresses to severe hypothalamic obesity, which results from hypothalamic injury caused either by the tumor itself or by therapeutic interventions. Hypothalamic obesity should be regarded as one manifestation within the broader clinical spectrum of hypothalamic syndrome. Given the pivotal role of hypothalamic nuclei in maintaining physiological homeostasis, hypothalamic syndrome encompasses a wide range of disturbances, including hypothalamic-pituitary hormone deficiencies, disruption of circadian rhythms, impaired regulation of hunger, satiety, and thirst, as well as thermoregulatory dysfunction and cognitive, sleep-related, and psychosocial impairments. Consequently, affected individuals often develop persistent obesity, chronic fatigue, excessive daytime sleepiness, and mood disturbances, which may contribute to social withdrawal, academic challenges, reduced participation in daily activities, and impaired quality of life. Over time, these patients are at increased risk for metabolic syndrome, cardiovascular disease, sustained reductions in quality of life, and premature mortality. Historically, the management of hypothalamic syndrome has been challenging for both patients and clinicians, as conventional obesity treatments, including lifestyle modification, dietary interventions, and physical activity, have shown limited long-term efficacy. Pharmacological approaches have likewise been unsatisfactory, either due to insufficient effectiveness or unacceptable adverse effects leading to their withdrawal from clinical use. The therapeutic impact of central nervous system stimulants and glucagon-like peptide-1 receptor agonists in acquired hypothalamic obesity remains inconsistent and subject to ongoing debate. Recent findings from a randomized controlled trial provide, for the first time, encouraging evidence that setmelanotide, a melanocortin-4 receptor agonist, may substantially improve outcomes in patients with hypothalamic dysfunction associated with hypothalamic obesity. The emergence of a safe and effective pharmacological therapy that addresses not only metabolic abnormalities but also key psychosocial features, such as hyperphagia and overall quality of life, may represent a significant advancement in the management of this complex condition and offers the potential to meaningfully improve outcomes in this highly burdened and underserved patient population.
Perinatal Semaglutide Treatment Improves Maternal Health and Mitigates Offspring Metabolic Dysfunction in a Mouse Model of Maternal Obesity.
bioRxiv
Ananthi Rajamoorthi, Taylor Hollingsworth, Yuxia Guan +2 more
Early-life exposures during critical periods of development significantly impact lifelong metabolic risk and likely contribute to the rising rates of obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD) in children. Here, we evaluated the safety and metabolic effects of semaglutide, a GLP-1 receptor agonist (GLP-1 RA), administered from preconception through lactation in dams fed a high-fat diet (HFD) or standard diet, and assessed metabolic outcomes in dams and their offspring. Offspring were weaned to a standard diet. We found that semaglutide improved body composition and glucose metabolism in HFD-fed dams during pregnancy. These maternal changes persisted 10 weeks after weaning despite discontinuation of semaglutide treatment. HFD exposure impaired glucose homeostasis and promoted hepatic steatosis in offspring at 18 weeks. These effects were ameliorated by maternal semaglutide treatment. Importantly, metabolic improvements in dams and offspring occurred without adverse effects on conception rate or fetal viability. These findings suggest that GLP-1 RA during the perinatal period can improve maternal and offspring metabolic health in a mouse model of obesity and support further investigation of GLP-1-based therapies to mitigate maternal metabolic dysfunction and improve metabolic risk in children.
Prescribing of GLP-1 and GIP/GLP-1 Receptor Agonists and Other Glucose-Lowering Drugs Requiring Special Caution in Elderly Japanese People With Type 2 Diabetes: A Preliminary Report.
J Clin Med Res
Manaka Sato, Riku Takemura, Masahiro Yuki +4 more
Adverse drug events are more common in elderly people, prompting the Japan Geriatrics Society to update its "Guidelines for Safe Pharmacotherapy in the Elderly" in 2025. In this revision, glucagon-like peptide-1 receptor agonist (GLP-1RA) and glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1RA) were newly added to the list of drugs requiring special caution. This study aimed to descriptively investigate real-world prescribing patterns of GLP-1RAs and their concomitant use with other glucose-lowering drugs (GLDs) requiring special caution among elderly people with type 2 diabetes (T2D).
Obesity Management Pharmacotherapies and Lifestyle Treatment for Pediatric Obesity Management: A Systematic Review and Network Meta-Analysis.
JAMA Pediatr
Ke-Wen Wan, Evander Fung-Chau Lei, Ying Liu +6 more
Pediatric obesity is a global health challenge. Although health behavior and lifestyle treatment (HBLT) is foundational, the comparative effectiveness of HBLT, various pharmacotherapies, and their combinations remains unclear.