Limited · human
This retrospective, real-world study used the TriNetX federated database to compare oncologic outcomes in postmenopausal women aged ≥50 with obesity (BMI ≥30) and stage 0–III breast cancer, across three groups: GLP-1 receptor agonist (GLP-1RA) users, bariatric surgery patients, and those receiving both interventions. Two propensity score–matched analyses (1:1) adjusted for age, BMI, tumor stage, receptor status, adjuvant therapy, and comorbidities. Study 1 (n=3,438 matched per group) found that GLP-1RA users had a lower instantaneous mortality risk (HR 0.57, 95% CI 0.45–0.73) and lower locoregional recurrence (LRR) rate (1.8% vs. 4.7%; HR 0.52) compared to bariatric surgery alone, despite similar 10-year overall survival (87% vs. 83%). Study 2 (n=1,129 matched per group) found that combined bariatric surgery plus GLP-1RA therapy was associated with higher 10-year overall survival (91% vs. 80%; HR 0.44) and lower LRR (2.5% vs. 5.8%; HR 0.52) versus surgery alone. The authors hypothesize potential anti-inflammatory, insulin-modulating, or other metabolic mechanisms beyond weight loss. Key limitations include the observational design, potential residual confounding, lack of GLP-1RA dose/duration data, and inability to establish causality.
Annals of surgery · Jun 2026DOI ↗ Review
This review examines the evolving medical management of short bowel syndrome intestinal failure (SBS-IF), a condition historically associated with lifelong dependence on home parenteral support (HPS) and, in select cases, intestinal transplantation (iTx). The authors describe how recent pharmacological advances—particularly glucagon-like peptide-2 (GLP-2) analogues and GLP-1 receptor agonists—have been integrated alongside conventional antimotility and antisecretory therapies to promote intestinal adaptation. The review argues that SBS-IF should now be understood as a dynamic and potentially modifiable form of organ failure rather than a static, irreversible condition. According to the authors, GLP-2 analogues represent the first pathophysiology-targeted, pro-adaptive therapies in this disease, while GLP-1 receptor agonists are highlighted as promising adjuncts, especially for patients with high-output phenotypes. The paper contends that multidisciplinary intestinal rehabilitation and gut-directed pharmacotherapy have meaningfully altered the natural history of SBS-IF, reducing HPS dependence and improving patient-centered outcomes. A key implication discussed is that iTx has been repositioned from a default end-stage intervention to a targeted rescue option used after optimized rehabilitation. Limitations include the review format, which synthesizes existing literature without presenting new primary data or meta-analytic pooling.
Current opinion in organ transplantation · Jun 2026DOI ↗ InsufficientPreprint
This bibliometric study compared the 100 most-cited articles on GLP-1 receptor agonists (GLP-1RA) with the 100 most-cited articles on metabolic bariatric surgery (MBS), using the Bibliometrix software to analyze citation patterns, journal distribution, and journal impact factors (IF). The study found that GLP-1RA articles accumulated more total citations (91,660 vs. 72,243) and had a higher median citation count (718 vs. 551) than MBS articles. GLP-1RA research was also more internationally collaborative (57% vs. 26%) and appeared more frequently in journals with IF above 40 (41% vs. 25%). The weighted 5-year mean IF was substantially higher for GLP-1RA journals (35.4 vs. 21.6). The authors argue that these differences may reflect a "prestige-journal effect," whereby GLP-1RA trials' placement in flagship journals such as the NEJM and Lancet inflates citation counts relative to MBS research, which is more dispersed across surgical specialty journals. A key limitation is that this study analyzes publication patterns rather than clinical outcomes, and cannot establish whether citation differences reflect true differences in scientific merit. The authors conclude that journal-impact inequalities should be considered when making citation-based comparisons between therapeutic fields.
Unknown journal · Jun 2026DOI ↗ Animal only
This systematic review (PRISMA-guided) examined whether GLP-1 receptor agonists (GLP-1 RAs) exert neuroprotective effects in preclinical models of stroke and Parkinson's disease (PD). Researchers searched four major databases (Cochrane CENTRAL, PubMed, Web of Science, Scopus), identifying 1,643 records and ultimately including 13 experimental animal studies published between 2013 and 2026. For stroke, studies primarily used middle cerebral artery occlusion (MCAO) models; the review found that agents such as liraglutide and linagliptin were associated with notable reductions in infarct volume and improved neurological deficit scores in treated animals. For PD models, the included studies reported improvements in motor function, preservation of dopaminergic neurons, and reduced α-synuclein aggregation. Across both disease models, GLP-1 RAs appeared to modulate neuroinflammatory markers (TNF-α, IL-1β, IL-6), oxidative stress indicators (ROS, 4-HNE), and apoptotic pathways (increased Bcl-2, decreased Bax). Risk of bias assessment using the SYRCLE tool rated overall quality as moderate, with four studies flagged as high risk due to small sample sizes and inadequate reporting of randomization and blinding procedures. The authors concluded that while preclinical evidence appears promising, standardized studies and clinical trials are needed before translational conclusions can be drawn.
Disease-a-month : DM · Jun 2026DOI ↗ Animal only
This study developed a targeted nanodelivery system — GLP-1@tMSN (glucagon-like peptide-1 loaded into matrix metalloproteinase-2-targeted mesoporous silica nanoparticles) — designed to mobilize endothelial progenitor cells (EPCs) and promote re-endothelialization following coil embolization of intracranial aneurysms (IAs). Using a rat coiled aneurysm model, the researchers evaluated whether the platform could recruit EPCs to the lesion site and accelerate vascular repair. The study found that GLP-1@tMSN significantly enhanced EPC recruitment and re-endothelialization compared to controls. After 28 days, histological analysis showed formation of mature endothelial-like tissue in treated animals, while controls exhibited fibrous tissue. Immunofluorescence confirmed preferential accumulation of CD34+VEGFR2+ EPCs at the lesion site, alongside activation of the Wnt/β-catenin signaling pathway, which the authors implicate as a key driver of vascular repair. Preliminary biocompatibility assessments suggested an acceptable safety profile. Limitations include the exclusive use of a rat model, a single 28-day follow-up endpoint, small experimental scale, and lack of human translational data. The authors conclude that this nanotherapeutic approach may hold promise for reducing long-term IA recurrence after embolization, though clinical validation is needed.
Journal of neurosurgery · Jun 2026DOI ↗ In vitro
This study presents a novel chemical strategy for delivering protein-degrading molecules (PROTACs) selectively to pancreatic β-cells by exploiting the glucagon-like peptide-1 receptor (GLP-1R). The researchers engineered a modified GLP-1 peptide using a tryptophan-mediated multicomponent Petasis reaction (TMPR), a modular "stapling" technique that locks the peptide into a stable α-helical conformation. This stapled analogue was reported to show enhanced structural stability and improved GLP-1R potency compared with the wild-type peptide. The stapling strategy also incorporated a chemical handle allowing conjugation to a PROTAC — a bifunctional molecule designed to degrade bromodomain-containing protein 4 (BRD4), a transcriptional regulator implicated in various diseases. The resulting GLP-1–PROTAC conjugate reportedly retained GLP-1R agonist activity and selectively induced BRD4 degradation in GLP-1R-expressing cells, consistent with receptor-mediated uptake and intracellular degrader activation. The study was conducted entirely in cellular (in vitro) systems; no animal or human data were reported. Key limitations include the absence of in vivo validation, and the translational relevance to human β-cell biology remains to be established.
Angewandte Chemie (International ed. in English) · Jun 2026DOI ↗ Animal only
This study investigated whether sustained GLP-1 gene delivery could stimulate β-cell regeneration in diabetic rats, and whether regenerative responses differ between neonatal and adult stages. Researchers engineered a third-generation HIV-based lentiviral vector encoding native GLP-1 (LentiGLP-1) under a CMV promoter. Two rat models of type 2 diabetes were used: neonatal rats treated with low-dose streptozotocin (STZ) to exploit developmental pancreatic plasticity, and adult rats subjected to a high-fat diet combined with low-dose STZ. In neonatal diabetic rats, LentiGLP-1 administration markedly promoted differentiation of ductal and progenitor cells into insulin-producing β-cells, accompanied by increased β-cell proliferation. In adult diabetic rats, LentiGLP-1 partially restored β-cell populations via activation of residual progenitors and stimulation of existing β-cell replication, with improvements in glycemic control and insulin sensitivity. Acinar cells were not observed to contribute to β-cell regeneration in either model. A key limitation is that findings are entirely in rodents, and the translational relevance to human β-cell biology remains unestablished. The study provides mechanistic insight into developmentally regulated GLP-1 effects but does not constitute evidence of efficacy in humans.
Journal of molecular medicine (Berlin, Germany) · Jun 2026DOI ↗ Limited · human
This pharmacovigilance study analyzed over 58 million adverse event reports from the FDA Adverse Event Reporting System (FAERS, 2004–2025) and cross-validated findings against the Canada Vigilance Adverse Reaction Online Database (CVARD) to identify drugs associated with delayed gastric emptying and gastroesophageal reflux. Using three signal-detection algorithms — Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) — the study screened 50 drugs and found 20 with positive signals across all three methods. GLP-1 receptor agonists showed the strongest associations, with semaglutide exhibiting the highest signal for impaired gastric emptying (ROR: 80.27). Other drug classes flagged included insulin formulations (notably insulin degludec), bisphosphonates, angiotensin receptor blockers, and trofinetide. Weibull time-to-onset analysis further characterized temporal patterns, ranging from very early onset (trofinetide, median ~6.6 days) to markedly delayed onset (immunoglobulin G, median ~535 days). Key limitations include the inherent reporting biases of spontaneous pharmacovigilance databases, inability to establish causality, and potential confounding by indication or co-medications. The authors suggest findings should inform enhanced pharmacovigilance and clinical monitoring strategies.
Limited · human
This case report describes a woman in her 50s who developed Boerhaave's syndrome (spontaneous full-thickness esophageal perforation) in the context of GLP-1 receptor agonist (GLP-1 RA) use — specifically semaglutide restarted abruptly at the maximum weekly dose after several months off therapy. She presented with vasopressor-dependent shock, respiratory failure, pneumomediastinum, and bilateral pleural effusions. An esophagram confirmed a contained esophageal perforation. Initial management included endoscopic stent placement, nasojejunal feeding, and chest tube drainage with early improvement. Two months later she was readmitted with necrotizing pneumonia, esophagopleural fistula, stent migration, and abscess, requiring left thoracotomy, decortication, abscess drainage, lung wedge resection, and intercostal muscle flap repair. At 10-month follow-up, the esophagus had healed on endoscopy. The authors propose that GLP-1 RA–induced gastroparesis contributed to forceful emesis and transmural rupture. Key limitations include the inherent inability to establish causality from a single case, and the absence of a control group or systematic population-level data linking GLP-1 RAs to esophageal perforation.
Journal of cardiothoracic surgery · Jun 2026DOI ↗ Review
This article provides practical, evidence-informed clinical guidance on incorporating oral semaglutide — the first oral glucagon-like peptide-1 (GLP-1) receptor agonist — into obesity management. The authors draw on data from clinical trials, including the OASIS 4 trial, as well as expert clinical insights. The paper highlights that oral semaglutide has demonstrated weight loss outcomes comparable to subcutaneous GLP-1 therapies, with associated improvements in cardiometabolic risk factors, and has received regulatory approval for obesity management and cardiovascular risk reduction in adults. A central focus is the formulation's strict administration requirements, which are necessary to optimize absorption and bioavailability. The article emphasizes the importance of person-centered consultations between healthcare professionals and patients prior to treatment initiation, covering realistic expectations, adherence strategies, and adverse event management. Key limitations include that this is a guidance/review article rather than a primary clinical trial, meaning its conclusions reflect the authors' synthesis and interpretation of existing evidence rather than new experimental data. It does not establish independent causal efficacy and is subject to potential expert bias.
Postgraduate medicine · Jun 2026DOI ↗ Limited · human
This retrospective cohort study examined how the timing of preoperative semaglutide discontinuation affects short-term surgical outcomes in patients undergoing aesthetic lipoabdominoplasty. Eighty non-diabetic patients were divided into four groups: those who continued semaglutide until the day of surgery (Group A), those who discontinued 2 weeks prior (Group B), those who discontinued 4 weeks prior (Group C), and semaglutide-naïve controls (Group D). Groups were matched for age, BMI, and surgical technique, and 30-day postoperative complications were tracked. The study found that Group A had the highest complication rate at 45%, encompassing wound dehiscence, infection, and seroma formation. Group B showed a moderate reduction (30%), while Group C's complication rate (10%) was comparable to the control group (10%). Gastrointestinal intolerance and prolonged drain duration were also more common among patients with recent or ongoing semaglutide use. No reoperations or readmissions were recorded. The authors concluded that a 4-week preoperative discontinuation window effectively normalizes complication rates. Key limitations include the retrospective design, small sample size (n=80 across four groups), and the absence of randomization, blinding, or long-term follow-up.
Aesthetic plastic surgery · Jun 2026DOI ↗ Limited · human
This cross-sectional pharmacovigilance study analyzed 142,705 adverse event (AE) reports for GLP-1 receptor agonists (GLP-1 RAs) from the FDA Adverse Event Reporting System (2015–2025), focusing on 4,090 reports linked to obesity indications. The authors found gastrointestinal events were most common, 76% of reports involved female patients, and most events onset within 0–30 days. Semaglutide showed a distinct distribution including a higher proportion of late-onset events (≥360 days), while tirzepatide showed negative reporting odds ratios for several gastrointestinal events. Strong disproportionality signals were identified for biliary, pancreatic, renal, and coagulation events. Separately, the study constructed herb-compound-target-AE networks using HERB 2.0 and the Comparative Toxicogenomics Database, applying graph convolutional network (GCN) modeling to identify herbal candidates—including Liquorice Root, Mulberry Leaf, Dahurian Angelica Root, Danshen Root, and Ginkgo Leaf—potentially associated with GLP-1 RA AE profiles. GCN performance was moderate (AUC-ROC 0.666–0.798). The authors explicitly note findings are exploratory and hypothesis-generating, with results limited by spontaneous reporting biases and computational modeling constraints. Independent experimental and clinical validation is required before any clinical application.
Scientific reports · Jun 2026DOI ↗ Moderate · humanPreprint
This Bayesian network meta-analysis systematically evaluated the dose-dependent efficacy and safety of mazdutide — a dual GLP-1 receptor and glucagon receptor agonist — in adults with obesity or overweight, with or without type 2 diabetes. Researchers searched five major databases through January 2026 and included nine randomized controlled trials comprising 2,292 participants. The study found that, compared with placebo, multiple mazdutide doses were associated with statistically significant improvements across a broad range of cardiometabolic outcomes, including body weight, waist circumference, BMI, HbA1c, fasting plasma glucose, blood pressure, LDL cholesterol, and liver enzymes (ALT). Subgroup analyses suggested that weight loss effects were more pronounced in non-diabetic individuals, while glycemic benefits were greater in those with type 2 diabetes. Gastrointestinal adverse events were notably more frequent with mazdutide relative to placebo, though serious adverse events were not significantly elevated. Key limitations include the relatively small number of included trials (n=9) and total participants, the indirect comparisons inherent to network meta-analysis methodology, potential heterogeneity across trial populations, and the preprint status of this work, meaning it has not yet undergone formal peer review.
Unknown journal · Jun 2026DOI ↗ In vitro
This study describes the development of a scalable, chemically defined protocol for differentiating human pluripotent stem cells (hPSCs) into hypothalamic neurons enriched for pro-opiomelanocortin (POMC)-expressing cells, which are key regulators of appetite, energy, and glucose balance. The researchers validated neuronal identity using multiple high-resolution techniques — including MERFISH single-cell transcriptomics, RNA-Seq, and ATAC-Seq — and benchmarked results against human hypothalamic tissue. The protocol was tested across multiple hPSC lines and demonstrated consistent induction of ventral diencephalon and hypothalamic markers, and was designed to be compatible with robotic, high-throughput cell culture platforms. Functional assays showed that derived neurons responded to insulin and the GLP-1 receptor agonist Exendin-4, and displayed transcriptional changes under altered glucose conditions. ATAC-Seq analysis identified candidate regulatory genomic regions associated with hypothalamic development and metabolic traits, and BMI-associated gene enrichment was observed in the derived neurons. Limitations include that this is an in vitro cell model and may not fully recapitulate the complexity of the intact human hypothalamus. No human clinical outcomes were assessed. The platform is positioned as a tool for studying the mechanisms underlying metabolic disease and for therapeutic screening.
Stem cell reports · Jun 2026DOI ↗ Limited · human
This clinical trial examined whether short-term meal replacement therapy (MRT) could reduce liver fat and improve metabolic markers in adolescents with severe obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Seventeen participants aged 12–17 years (mean BMI ~40 kg/m²; mean hepatic fat fraction ~15.6%) completed a 4–8 week MRT program targeting a ~500 kcal/day caloric deficit and at least 5% BMI reduction. Liver fat was measured using magnetic resonance spectroscopy (MRS) at baseline and follow-up. The study found a mean 5.6% absolute reduction in BMI and a statistically significant decrease in hepatic fat fraction, along with improvements in insulin sensitivity, glucose area under the curve, and leptin levels. No significant change in alanine aminotransferase (ALT) was observed. Key limitations include the very small sample size (n=17), absence of a control group, and the short intervention duration, all of which substantially restrict generalizability. The authors conclude that MRT was associated with reductions in liver fat and metabolic improvements in this population and call for larger, controlled trials to assess MRT as part of a broader multimodal treatment strategy for adolescent MASLD.
Childhood obesity (Print) · Jun 2026DOI ↗ Animal only
This preclinical study designed and tested a novel unimolecular dual agonist that combines glucagon-like peptide-1 (GLP-1) and fibroblast growth factor-21 (FGF21) into a single molecule, connected by a thermally responsive elastin-like polypeptide linker intended to form a sustained-release subcutaneous depot. Receptor activity was first confirmed in cell-based assays. The molecule was then tested in male C57Bl/6J mice fed a diet designed to induce advanced metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis. The study found that treated mice showed improvements in body weight, liver mass, blood glucose, and cholesterol compared to controls. Histological and molecular analyses indicated reductions in liver fat accumulation, inflammation, and fibrosis, along with decreased expression of inflammatory and fibrotic marker genes and increased hepatocyte proliferation. Limitations include the exclusive use of a single male mouse strain, the absence of female animals, and the inherent translational gap between diet-induced rodent models and human MASH. No human data were generated. The authors conclude that this dual-agonist approach warrants further development as a potential chronic liver disease therapy.
Communications medicine · Jun 2026DOI ↗ Limited · human
This observational matched case-control study used high-field (7 T) ¹H/³¹P magnetic resonance spectroscopy (MRS) to examine skeletal muscle metabolism in newly diagnosed, treatment-naïve people with multiple sclerosis (PwMS) compared to matched healthy controls. Gastrocnemius muscle was assessed both at rest (static MRS) and during post-exercise recovery (dynamic ³¹P-MRS), alongside systemic metabolic profiling via an oral glucose tolerance test (OGTT) measuring glucose, insulin, and GLP-1. The study found that PwMS showed lower resting carnosine levels, elevated pre-exercise inorganic phosphate (Pi), a trend toward a reduced phosphocreatine-to-Pi ratio, and significantly prolonged post-exercise phosphocreatine (PCr) recovery — all indicators of mitochondrial energetic impairment. PwMS also demonstrated a blunted GLP-1 response during OGTT despite preserved insulin sensitivity. Notably, higher PCr levels correlated with greater GLP-1 response only in PwMS, suggesting a muscle-systemic metabolic link specific to the disease. The authors conclude that skeletal muscle mitochondrial dysfunction is detectable at MS onset, even before significant systemic metabolic disruption occurs. Limitations include relatively small sample size, a single muscle group assessed, and the cross-sectional design precluding causal inference.
Scientific reports · Jun 2026DOI ↗ Review
This narrative review examines the potential ocular effects of geroprotective agents — pharmacologic compounds studied for longevity and systemic aging benefits — with a focus on their relevance to age-related eye diseases including age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal vein occlusion (RVO), and glaucoma. The authors argue that shared mechanisms of neurodegeneration, microvascular injury, and chronic inflammation underlie both systemic aging and major retinal diseases, making geroprotectors a pharmacologically relevant class for ophthalmic consideration. The review covers a broad range of agents: GLP-1 receptor agonists, metformin, SGLT-2 inhibitors, statins, cannabinoids, calcium channel blockers, spermidine, taurine, NAD+ precursors, rapamycin, and mifepristone. The authors note that GLP-1 receptor agonists have been associated with potential glaucoma risk reduction but also with unconfirmed reports of nonarteritic anterior ischemic optic neuropathy. The review acknowledges that ocular effects of these agents are incompletely characterized, variably reported, and sometimes controversial. Key limitations include reliance on heterogeneous observational and preclinical data, absence of dedicated ophthalmic clinical trials, and potential confounding in real-world studies. The authors aim to support clinical awareness and identify gaps for future investigation.
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · Jun 2026DOI ↗ Review
This narrative review proposes a novel conceptual framework for integrating GLP-1 receptor agonists (GLP-1 RAs) into bariatric surgical care, drawing an analogy from oncology's neoadjuvant and adjuvant treatment models. The authors suggest that GLP-1 RAs used before surgery ("neoadjuvant") could reduce perioperative risk—particularly in super-obese patients—by promoting early weight loss and improving dyslipidemia. Used after surgery ("adjuvant"), GLP-1 RAs may address weight regain and sustain metabolic improvements in patients with suboptimal surgical outcomes. The review synthesizes findings from prospective trials, retrospective analyses, and meta-analyses, noting that preoperative GLP-1 RA use appears generally safe but requires monitoring for metabolic adaptation and a potential "ceiling effect" on postoperative results. The authors introduce a proposed "perioperative management ladder" as a structured decision-making tool. Importantly, the framework is described as primarily hypothesis-generating and intended to inform the design of future randomized controlled trials. Key limitations include the review's narrative (non-systematic) methodology, reliance on heterogeneous primary studies, and the absence of original data.
Current obesity reports · Jun 2026DOI ↗ Limited · human
This systematic review and meta-analysis examined whether glucagon-like peptide-1 receptor agonists (GLP-1RAs) — medications commonly used for type 2 diabetes and obesity — are associated with an increased risk of diabetic macular edema (DME). Researchers searched five major databases through October 2025 and ultimately included 13 retrospective cohort studies (published 2021–2025) drawn from large real-world databases, all involving patients with diabetes who did not have DME at baseline. Using random-effects models, the study found that the pooled incidence proportion of new-onset DME among GLP-1RA users was approximately 14%. Compared with mixed antihyperglycemic therapies, GLP-1RA use was not significantly associated with increased DME risk (HR: 0.81, 95% CI: 0.52–1.26). GLP-1RAs were associated with a higher relative risk of DME compared to SGLT-2 inhibitors (HR: 1.50, 95% CI: 1.17–1.94), but not compared to DPP-4 inhibitors. The authors rated the overall certainty of evidence as very low, citing high statistical heterogeneity (I² = 99.8%), reliance on retrospective observational designs with inherent confounding risks, and variability across database sources. The study concluded that current evidence does not support a clear overall increased DME risk with GLP-1RA use but called for prospective studies to better characterize comparative retinal safety.
Canadian journal of ophthalmology. Journal canadien d'ophtalmologie · Jun 2026DOI ↗