Target Trial of Glucagon-Like Peptide-1 Agonists versus Dipeptidyl Peptidase-4 Inhibitors and Mortality in Hemodialysis.

Insulin resistance and related metabolic disorders are becoming increasingly common among women of reproductive age. However, the mechanisms by which insulin signaling influences female fertility remain only partially understood. Currently, there is rapid growth in the use of new insulin-sensitizing medications, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, prescribed to women who may want to conceive, raising concerns about reproductive safety and benefits. Insulin acts at multiple points along the hypothalamic-pituitary-gonadal axis, including ovulatory function, oocyte maturation, and endometrial receptivity. Conditions such as polycystic ovary syndrome, diabetes, or obesity may impair oocyte development, modify IVF success rates, and compromise embryo implantation. Emerging evidence suggests that both SGLT2 inhibitors and GLP-1 receptor agonists improve factors such as ovulatory function and androgen balance, though both carry safety concerns during the periconception period. Clinicians managing women of reproductive age with insulin-related metabolic disorders should incorporate reproductive counseling into treatment planning. Ultimately, fertility-focused trials of newer insulin modifiers may be beneficial.

Change in circulating irisin level and its association with lipid metabolism after exenatide treatment in patients with type 2 diabetes mellitus.

Short bowel syndrome intestinal failure (SBS-IF) occupies a unique position at the interface between chronic organ failure management and intestinal transplantation (iTx). Historically, patients with SBF-IF progressed inevitably toward lifelong home parenteral support (HPS) dependence and, in a small and highly selected subset with impending HPS failure, ultimately to iTx. Recent advances in pro-adaptive pharmacological strategies, focusing on glucagon-like peptide (GLP)-2 and GLP-1-based approaches as adjuncts to conventional antimotility and antisecretory therapies, are reviewed, with implications for decision-making across the SBS-IF disease trajectory presented. SBS-IF is now recognized as a dynamic and modifiable form of organ failure. Targeted pro-adaptive interventions reduce HPS dependence and improve patient-centered outcomes. Conventional antimotility and antisecretory therapies remain foundational, whereas GLP-2 analogues are the first pathophysiology-targeted, pro-adaptive therapies in SBS-IF, while GLP-1 receptor agonists have emerged as promising adjuncts in selected patients, particularly those with high-output phenotypes. Multidisciplinary intestinal failure rehabilitation and gut-directed pharmacotherapy have altered the natural history of SBS-IF. Medical rehabilitation has shifted iTx from a default end-stage therapy to a targeted rescue option reserved for irreversible HPS failure, to be considered after optimized rehabilitation but before the transplant window is lost.

GLP-1 receptor agonists at the crossroads of obesity and addiction: A review of shared neurobiology and translational evidence.

Gut-liver metabolic and enterohormonal remodeling drives progression from metabolic dysfunction-associated steatotic liver disease to steatohepatitis.

Glucagon-like peptide-1 receptor agonist use and risk of gynecologic cancers: a meta-analysis of multinational real-world cohort studies.

GLP-1 Receptor Agonist Use Is Associated with Venous Ulcer Healing and Fewer Wound Infections.

The neuroprotective properties of several anorexigenic peptides, including leptin and glucagon-like peptide-1, are well established across models of neurodegenerative diseases. However, less is known about the role of orexigenic neuropeptides-including neuropeptide Y, agouti-related peptide, melanin-concentrating hormone, orexins, galanin, and peripherally released hormone ghrelin-that are best known for their role in energy balance and stimulation of food intake. Growing evidence highlights their broader neuroprotective properties across preclinical models of Alzheimer's disease (AD) and Parkinson's disease (PD). In AD, these peptides reduce hallmark pathologies such as amyloid burden, tau phosphorylation, oxidative stress, and neuroinflammation, while enhancing synaptogenesis, neurogenesis, and cognitive function. In PD models, ghrelin protects nigrostriatal dopaminergic neurons by restoring autophagic flux, suppressing endoplasmic reticulum stress-mediated apoptosis, and reducing microglial activation, whereas orexin A and B preserve tyrosine hydroxylase expression, promote neuronal excitability, and improve motor and cognitive outcomes. Taken together, these findings position orexigenic peptides as promising modulators of neurodegeneration and highlight their potential as therapeutic targets in AD and PD.

Novel gastroprotective role of Alogliptin: Modulating the GDNF/PI3K/Akt/GSK3β, SDF-1/CXCR4, and CREB/COX-2/PGE2 signalling pathways to ameliorate diclofenac-induced peptic ulcer in rats.

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

Dendrobium huoshanense polysaccharides alleviate DSS-induced ulcerative colitis in mice: comparison between different parts of plant and role of GLP-1/GLP-1R axis.

The glucagon-like peptide-1 receptor agonist, Ex4, reduces intromission in sexually experienced male mice.

Peripheral artery disease (PAD) affects >236 million people globally, particularly among those with type 2 diabetes. GLP-1 (glucagon-like peptide-1) receptor agonists (GLP-1 RAs) offer cardiovascular and kidney benefits, but their impact on PAD-specific outcomes is underexplored. This study evaluates long-term GLP-1 RA effects on adverse outcomes in this population. A retrospective cohort study using the TriNetX platform (January 1, 2010-January 1, 2025) included patients with both PAD and type 2 diabetes prescribed either GLP-1 RAs or metformin, excluding those with recent cardiovascular events, end-stage renal disease, or prior amputations. Propensity score matching was performed to account for confounding. Outcomes at 5 years included mortality, myocardial infarction, hospitalization, stroke, revascularization, amputations, dialysis, major adverse cardiovascular events, and kidney events. After matching, 2133 patients per cohort were analyzed in the overall group with PAD. At 5 years, GLP-1 RA therapy was associated with lower mortality (10.31% versus 14.49%; hazard ratio [HR], 0.74 [95% CI, 0.62-0.88]; P=0.0005), hospitalization (69.3% versus 74.7%; HR, 0.87 [95% CI, 0.81-0.94]; P=0.0002), revascularization (4.69% versus 7.27%; HR, 0.64 [95% CI, 0.50-0.82]; P=0.0004), major amputation (2.30% versus 4.36%; HR, 0.52 [95% CI, 0.37-0.74]; P=0.0002), and minor amputation (4.03% versus 6.42%; HR, 0.63 [95% CI, 0.48-0.83]; P=0.0007). major adverse cardiovascular events, myocardial infarction, stroke, and major adverse kidney events were similar between groups. GLP-1 RAs were associated with lower rates of mortality, major amputation, revascularization, and hospitalization in PAD and type 2 diabetes patients. These findings support prioritizing GLP-1 RAs for limb-specific and cardiovascular outcomes in this high-risk group.

Glucagon-like peptide-1 (GLP-1) is a key incretin hormone regulating insulin secretion, appetite, and energy balance. Recent research highlights complex interactions between dietary composition, gut microbiome metabolism and GLP-1 secretion. Understanding these relationships is increasingly important given the widespread clinical use of GLP-1 receptor agonists for obesity and type 2 diabetes and the growing interest in microbiome-targeted nutritional strategies. Recent studies demonstrate that microbial metabolites mediate many nutritional effects on GLP-1 secretion. Fermentation of dietary fibres generates short-chain fatty acids (SCFAs) that stimulate GLP-1 secretion through FFAR2/FFAR3 signalling. Additional microbial metabolites can regulate enteroendocrine signalling, including indole derivatives, N-acyl glycines and bile acid metabolites. Human and preclinical studies show that dietary interventions such as β-glucan supplementation, fermentable carbohydrate diets, probiotics, polyphenols and plant polysaccharides can influence GLP-1 secretion through microbiome-dependent mechanisms. Evidence supports an interaction between nutrition, the gut microbiome and GLP-1 signalling. Microbial metabolites link dietary substrates to GLP-1 secretion and diet shapes the microbial communities producing them. Integrating microbiome profiling with dietary interventions may help optimise metabolic therapies and explain variability in responses to GLP-1-based treatments.

The association between glucagon-like peptide 1 receptor agonists therapy and outcomes after heart transplant.

Comprehensive drug safety assessment of sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and dipeptidyl peptidase 4 inhibitors: A Danish population-based active comparator new user cohort study.

Cystic fibrosis (CF) is a monogenic disorder leading to pulmonary disease, pancreatic insufficiency and cystic fibrosis-related diabetes (CFRD). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now being investigated in people with cystic fibrosis (pwCF) and CFRD. To date, their therapeutic potential has been almost exclusively studied in case reports or case series. These agents improved glycated haemoglobin (HbA1c) and continuous glucose monitoring (CGM) parameters. Benefits were also observed in weight reduction, particularly for subjects on cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI). However, discordant results have also been reported. Moreover, GLP-1RAs have improved pulmonary function, even following lung transplantation. Importantly, the dual glucagon-like peptide1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide has also yielded favourable outcomes. Finally, preliminary evidence suggests potential inhibition of bone resorption, pointing to a therapeutic perspective in cystic fibrosis-related bone disease (CFBD). However, potential adverse events should not be ignored. These include risk of acute pancreatitis, nausea/vomiting, nutritional depletion, bowel dysmotility and distal intestinal obstruction syndrome, as well as others. Adverse events should be addressed with caution, and dose adjustments may be useful. Large prospective multicentre studies are now required to validate these outcomes and to suggest implications for clinical practice.

Changes of gut microbiota, hormone and glycolipid metabolism by dietary fiber (oat bran) supplementation in patients with laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass: A randomized controlled study.

Tirzepatide, an injectable glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA), is approved for weight management in several regions. Oral GLP-1 RAs, such as semaglutide, are under investigation to improve convenience, acceptance and adherence versus injectable formulations. Currently, no studies have compared the efficacy and safety of tirzepatide with oral semaglutide for weight management. This study aimed to indirectly compare the efficacy and safety of weekly injectable tirzepatide 5, 10 and 15 mg for weight management in obesity and overweight versus daily oral semaglutide 50 mg. Pivotal trials SURMOUNT-1 (tirzepatide, Week 72) and OASIS 1 (oral semaglutide, Week 68) were compared using multilevel network meta-regression (ML-NMR) to adjust for differences in sex, ethnicity and outcome baselines between trial populations. Participants were adults without type 2 diabetes and with obesity (BMI ≥ 30 kg/m2), or overweight (BMI ≥ 27 kg/m2) with ≥ 1 obesity-related complication. Tirzepatide 10 and 15 mg were associated with statistically significantly greater reductions in weight (mean difference: -4.48% [-6.35, -2.61] and -5.59% [-7.52, -3.77]) and waist circumference (-3.60 cm [-5.59, -1.72] and -4.32 cm [-6.30, -2.40]), and higher odds of achieving ≥ 5%/10%/15%/20% weight reduction compared with oral semaglutide. Cardiometabolic benefits and safety profiles were improved or generally comparable for tirzepatide versus oral semaglutide. This ML-NMR provides an indirect comparison of injectable tirzepatide with oral semaglutide for weight management. Tirzepatide was associated with statistically significantly greater weight and waist circumference reduction versus oral semaglutide and improved or similar cardiometabolic benefits and safety.