🧪 TrialInsufficient
Registered Phase 4 interventional trial (not yet recruiting). Prediabetes affects millions of adults worldwide and carries a high risk of progression to type 2 diabetes. Mazdutide is a once-weekly injectable drug that activates both GLP-1 and glucagon receptors, lowering blood sugar and body weight simultaneously. This study (DREAM-PRE) tests whether mazdutide can help adults with prediabetes return to normal blood sugar levels. Approximately 150 adults aged 18-75 years with prediabetes and BMI ≥22 kg/m² will be randomly assigned in equal numbers to one of three groups: mazdutide 4 mg once wee
ClinicalTrials.gov · Jun 2026View trial ↗ 🧪 TrialInsufficient
Registered Phase 3 interventional trial (not yet recruiting). This is randomized, double-blind, placebo-controlled study of the long-term efficacy, safety, and tolerability of multiple doses of aleniglipron in participants living with overweight or obesity and T2DM. Participants will be randomized to aleniglipron or placebo for a total of 76 weeks of treatment.
ClinicalTrials.gov · Jun 2026View trial ↗ 🧪 TrialInsufficient
Registered N/A interventional trial (recruiting). The purpose of this study is to examine the effects of resistance exercise, such as weightlifting, on retention of muscle mass and mental health in individuals taking GLP-1 RAs (an obesity medication). Resistance exercise is focused on increasing the strength of participants' muscles, such as how much participant can lift. •The duration of this study is 3 months. This includes: * Orientation session to explain study protocol, exercise program, and complete questionnaire about participants' medical history and lifestyle. * Two health assessments
ClinicalTrials.gov · Jun 2026View trial ↗ 🧪 TrialInsufficient
Registered Phase 3 interventional trial (not yet recruiting). Study GSBR-1290-12 is a Phase 3 pivotal, multicenter, global, randomized, placebo-controlled, double-blind study to investigate the long-term efficacy, safety, and tolerability of 3 maintenance doses of aleniglipron once daily (QD) compared with placebo, when used in combination with a reduced-calorie diet and increased physical activity. All participants will be randomized to at least 76 weeks of treatment to evaluate the effects on long term body weight changes, tolerability, and safety. In addition, the study will compare the eff
ClinicalTrials.gov · Jun 2026View trial ↗ 🧪 TrialInsufficient
Registered observational trial (recruiting). Obesity is a chronic multifactorial disease with a strong genetic component. Although glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, such as tirzepatide, are highly effective treatments for obesity, substantial inter-individual variability in weight loss response remains. Genetic factors may contribute to these differences in treatment outcomes. The aim of this prospective cohort study is to investigate whether a Genetic Risk Score (GRS) and s
ClinicalTrials.gov · Jun 2026View trial ↗ 🧪 TrialInsufficient
Registered N/A interventional trial (active not recruiting). The goal of this clinical trial is to learn whether a mindfulness-based nutrition group program is feasible and acceptable for adults with obesity who are taking GLP-1 receptor agonist medication and receiving usual medical care, including dietetic counselling. The main questions this study aims to answer are: Can this group program be successfully carried out with adults receiving GLP-1 treatment? Do participants find the program useful, acceptable, and manageable? Are participants willing to attend the sessions, complete the home e
ClinicalTrials.gov · Jun 2026View trial ↗ 🧪 TrialInsufficient
Registered observational trial (recruiting). This study will assess the impact of genetic markers, microbiological (microbiome) and behavioral factors on tolerance, adherence and effectiveness of dual GLP1/GIP RA in the treatment of obesity. 200 consecutive patients who meet all inclusion and none of the exclusion criteria will be enrolled.
ClinicalTrials.gov · Jun 2026View trial ↗ 🧪 TrialInsufficient
Registered Phase 1/Phase 2 interventional trial (recruiting). Alzheimer's disease (AD) is the most common cause of dementia. Despite major research efforts, effective treatments that slow or stop disease progression remain limited. Growing evidence suggests that inflammation in the brain and the body plays a key role in the onset and progression of AD. In particular, immune cells called regulatory T cells (Tregs), which normally help control inflammation, are impaired in AD individuals. This leads to increased activity of harmful immune pathways that worsen brain injury. Interleukin-2 (IL-2) i
ClinicalTrials.gov · Jun 2026View trial ↗ 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 ↗