Review
This review examines the potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs) — including exenatide, semaglutide, dulaglutide, and the dual GLP-1R/GIP-R agonist tirzepatide — as pharmacological treatments for alcohol use disorder (AUD). The authors synthesized data from preclinical rodent and non-human primate studies, registered clinical trials, observational/pharmacoepidemiologic studies, and social media reports. In animal models, multiple GLP-1RAs were found to reduce alcohol consumption, alcohol-seeking behavior, alcohol-induced locomotor stimulation, reward memory, and relapse drinking, while also appearing to blunt alcohol's activation of the mesolimbic dopamine system. In the limited available human data, clinical trials of exenatide, semaglutide, and dulaglutide reported reductions in alcohol consumption, and pharmacoepidemiologic studies observed decreased rates of alcohol-related events among AUD patients prescribed GLP-1RAs or tirzepatide. The authors conclude that the GLP-1 system appears to be involved in AUD-related processes and that GLP-1RAs represent a promising but still tentative treatment avenue. Key limitations include the small number of human trials, heterogeneous study designs, and reliance on observational data for most clinical findings.
International journal of molecular sciences · May 2026DOI ↗ Review
This narrative review examines the potential role of incretin-based therapies in treating metabolic dysfunction-associated steatotic liver disease (MASLD), a condition strongly linked to metabolic syndrome and a leading cause of chronic liver disease. The authors highlight that no approved pharmacological treatments currently exist for MASLD and that progression to advanced fibrosis poses a significant clinical challenge. The review synthesizes evidence on GLP-1 receptor agonists, which the authors report have shown efficacy in reducing hepatic steatosis, inflammation, and fibrosis-related biomarkers, largely attributed to weight loss and improved insulin sensitivity. Dual agonists such as tirzepatide (GLP-1/GIP) are described as demonstrating superior hepatic and metabolic outcomes. Emerging agents including cotadutide (GLP-1/glucagon dual agonist) and retatrutide (GLP-1/GIP/glucagon triagonist) are presented as a novel frontier, with early clinical data suggesting potent hepatoprotective effects and favorable metabolic remodeling. The authors acknowledge that evidence on fibrosis progression remains limited. As a narrative review without systematic search methodology or meta-analysis, this paper is susceptible to selection bias and does not establish causality. It provides a useful synthesis of the current landscape but should be interpreted with appropriate caution.
Medicina (Kaunas, Lithuania) · May 2026DOI ↗ Limited · human
This retrospective observational study analyzed GLP-1 receptor agonist (GLP-1 RA) prescription records from the LUX MED private healthcare network in Poland between 2018 and 2025. Among 42,423 patients with more than one prescription, the study characterized how frequently patients switched between GLP-1 RA agents and identified factors associated with switching. The primary analysis used a discrete-time hazard model at the prescription-transition level, with subcutaneous semaglutide as the reference comparator. The study found that nearly 30% of patients switched agents at least once, and over 14% switched two or more times. After adjusting for switching opportunity and calendar time, liraglutide was associated with substantially lower odds of switching compared to subcutaneous semaglutide, while oral semaglutide and dulaglutide did not differ significantly. Temporal analyses revealed episodic peaks in switching and accelerating uptake of tirzepatide following its market entry. Key limitations include the retrospective, observational design; the lack of data on reasons for switching (e.g., tolerability, cost, availability); restriction to a single private-sector network; and the inability to establish causality. The authors characterize findings as hypothesis-generating.
Acta diabetologica · May 2026DOI ↗ Insufficient
This review examines the available information on dulaglutide, a GLP-1 receptor agonist used for type 2 diabetes management, in the context of breastfeeding safety. The authors note a complete absence of clinical data on dulaglutide use during lactation. They reason that, due to dulaglutide's large molecular weight of approximately 59,669 daltons as a protein molecule, transfer into breast milk is theorized to be minimal. Furthermore, even if trace amounts were present in milk, oral absorption by a nursing infant is considered unlikely because the compound would probably be degraded by proteolytic enzymes in the infant's gastrointestinal tract. Despite this theoretical reassurance, the authors conclude that caution is warranted when considering dulaglutide use during breastfeeding, with heightened concern for newborns and preterm infants, whose gastrointestinal systems may be less capable of fully degrading such compounds. The primary limitation of this review is the total lack of empirical human lactation data, meaning all conclusions are based on pharmacokinetic reasoning and extrapolation rather than direct measurement or clinical observation.
Unknown journal · May 2026Source ↗ Insufficient
This review article addresses the safety profile of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, specifically in the context of breastfeeding. The authors note that no empirical data are currently available on liraglutide use during lactation. The discussion is grounded in pharmacokinetic reasoning: liraglutide is a large peptide molecule with a molecular weight of 3,751 daltons, which suggests that transfer into breast milk would likely be minimal. Furthermore, even if trace amounts were present in milk, oral absorption by the nursing infant is considered unlikely, as the peptide would probably be degraded by proteolytic enzymes in the infant's gastrointestinal tract. Despite this theoretically low risk, the authors recommend caution when using liraglutide during breastfeeding, with particular attention to newborns and preterm infants, who may have less developed gastrointestinal and metabolic systems. The article acknowledges the absence of clinical or experimental data as a key limitation, meaning conclusions are based on indirect, mechanistic reasoning rather than direct observation or controlled study.
Unknown journal · May 2026Source ↗ Limited · human
This report examines the transfer of semaglutide into human breast milk in mothers using subcutaneous (injectable) semaglutide. The study found that semaglutide was undetectable in the breast milk of mothers receiving the drug via subcutaneous injection, and breastfed infants whose mothers used this route did not experience adverse effects. The report also highlights an important safety consideration regarding oral formulations of semaglutide (e.g., Rybelsus): these contain the absorption enhancer salcaprozate sodium (SNAC), which may be transferred into breast milk and potentially accumulate in nursing infants, raising concerns about the oral route during lactation. The report concludes that only injectable forms of semaglutide appear to be appropriate for use during breastfeeding based on currently available data. Limitations include the likely small number of mother-infant pairs studied and the observational nature of the data, which precludes definitive causal conclusions. Long-term infant outcomes were not assessed.
Unknown journal · May 2026Source ↗ 🧪 TrialInsufficient
Registered Phase 2 interventional trial (not yet recruiting). The goal of this phase IIc clinical trial is to learn if recombinant human thymosin beta 4 injection (NL005) works to treat heart damage in people who have had a serious type of heart attack called ST-segment elevation myocardial infarction (STEMI) and have been treated with emergency percutaneous coronary intervention (PCI, a procedure to open the blocked artery). It will also learn about the safety of NL005. The main questions it aims to answer are: * Does NL005 lower the size of permanent heart muscle damage measured by cardiac m
ClinicalTrials.gov · May 2026View trial ↗ Review
This narrative review synthesizes current evidence on glucagon-like peptide-1 (GLP-1)-based therapies—primarily semaglutide and tirzepatide—for the management of obesity-related heart failure with preserved ejection fraction (HFpEF). Drawing on PubMed and Scopus literature published between January 2020 and March 2026, the authors incorporated randomized trials, pooled analyses, mechanistic studies, and observational data. The review describes how obesity-related HFpEF arises from a complex interplay of excess lipids, chronic inflammation, and metabolic dysregulation, which also interact with GLP-1 pathways. According to the authors, GLP-1-based therapies demonstrated meaningful improvements in symptoms, exercise capacity, and quality of life in this population, with benefits attributed to weight reduction, decreased systemic inflammation, and improved congestion indices. Tirzepatide was additionally associated with reductions in heart failure-related complications. Proposed mechanisms include coordinated effects on metabolism, inflammation, hemodynamics, and cardiac remodeling. The authors note that evidence for improvements in morbidity appears stronger than evidence for reductions in mortality. Key limitations include the narrative (non-systematic) review methodology, potential selection bias in study inclusion, and the absence of long-term mortality data. The authors conclude that further research is needed to clarify long-term outcomes, refine patient selection, and guide clinical integration.
Journal of clinical medicine · May 2026DOI ↗ Review
This review examines the ocular effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual-incretin therapies, which are increasingly used for diabetes and obesity management. The authors synthesize experimental and clinical evidence across multiple ocular conditions. Preclinical data suggest plausible protective mechanisms, including antioxidant and neuroprotective effects on retinal and optic nerve tissues. In diabetic retinopathy, the review identifies transient early worsening as a key concern, attributed to rapid glycemic improvement rather than direct drug toxicity. A potential signal linking semaglutide to non-arteritic anterior ischemic optic neuropathy (NAION) is noted, though the authors characterize absolute risk as low and causality as unproven. Emerging associations are discussed for glaucoma, ocular surface diseases, and retinal vascular outcomes, while evidence on age-related macular degeneration and cataract is described as conflicting or preliminary. The authors conclude that ocular outcomes likely reflect an interplay of drug pharmacology, systemic metabolic changes, and individual patient factors rather than a uniform class effect. They suggest baseline ophthalmic assessment and individualized follow-up for high-risk patients, and call for prospective ophthalmology-focused trials. A key limitation is its reliance on heterogeneous and largely indirect evidence.
Vision (Basel, Switzerland) · May 2026DOI ↗ Review
This registry-based cross-sectional qualitative analysis examined the landscape of completed clinical trials investigating GLP-1 receptor agonists (GLP-1 RAs) for obesity, using data retrieved from ClinicalTrials.gov in October 2025. The authors identified 227 completed interventional studies and analyzed their design characteristics, research themes, and outcome domains. Liraglutide was the most studied agent (n = 86), followed by semaglutide and tirzepatide (n = 18 each) and exenatide (n = 15). Phase 3 and 4 trials predominated, though most studies enrolled fewer than 200 participants, suggesting relatively modest individual sample sizes. The authors reported a notable surge in completed trials after 2018, coinciding with the emergence of newer GLP-1 analogues. Primary outcomes were predominantly weight-related, but the synthesis identified a growing research focus on hepatic, cardiometabolic, and inflammatory endpoints. The study's key limitation is its registry-based, qualitative design — it does not synthesize individual-level patient outcome data or conduct meta-analysis, and therefore cannot draw conclusions about comparative efficacy or safety. Rather, it maps the structural and thematic evolution of the GLP-1 obesity research field. The authors conclude that the field is maturing beyond glycaemic and weight outcomes toward broader organ-specific endpoints.
Diabetes, metabolic syndrome and obesity : targets and therapy · May 2026DOI ↗ In vitro
This study investigated whether five FDA-approved glucagon-like peptide-1 receptor agonists (GLP-1RAs) — semaglutide, tirzepatide, liraglutide, and two others — could directly inhibit the aggregation of the 42-residue amyloid-β peptide (Aβ42), a key process implicated in Alzheimer's disease (AD). Using in vitro aggregation kinetics and microscopic analysis, researchers found that semaglutide, tirzepatide, and liraglutide inhibited Aβ42 aggregation, primarily by targeting the primary nucleation step — the initial formation of amyloid seeds. Semaglutide and tirzepatide delayed aggregation with submicromolar potency, while liraglutide showed the strongest suppression of primary nucleation and additionally modestly inhibited secondary nucleation. Liraglutide also altered fibril structure — producing less mature, more tortuous, and longer fibrils — and reduced the ability of fibrils to self-replicate (template). The study was conducted entirely in vitro (no cell, animal, or human data), which is a significant limitation for clinical translation. The authors conclude that certain GLP-1RAs can directly interfere with molecular steps of Aβ42 aggregation, and call for further studies to determine whether these mechanisms contribute to potential AD-protective effects observed in preclinical and clinical research.
Journal of the American Chemical Society · May 2026DOI ↗ Limited · human
This pilot observational study investigated the relationship between MOTS-c — a mitochondria-derived peptide — and cardiovascular risk markers in 32 stable peritoneal dialysis (PD) patients (mean age ~61 years, ~63% male). Researchers measured MOTS-c in three compartments: serum, urine, and peritoneal dialysate. Oxidative stress was assessed via plasma Advanced Oxidation Protein Products (AOPPs), and vascular stiffness was evaluated using carotid-femoral Pulse Wave Velocity (PWV), with echocardiography used to assess left ventricular systolic function. The study found that urinary MOTS-c was inversely correlated with AOPPs (suggesting a link to lower oxidative stress) and positively associated with PWV and left ventricular systolic function. Dialysate MOTS-c showed a strong inverse correlation with PWV and with both systolic and diastolic blood pressure, suggesting an association with a more favorable vascular profile. The authors propose a novel "Mitochondrial-Vascular Axis" in uremia and position MOTS-c as a potential biomarker. Key limitations include the very small sample size (n=32), pilot/cross-sectional design, single-center recruitment, and inability to establish causality from correlational data.
International urology and nephrology · May 2026DOI ↗ Animal only
This study investigated whether the mitochondrial-derived peptide MOTS-c could protect the neonatal heart from hyperoxia-induced injury. Using neonatal mice exposed to 85% oxygen as an in vivo model and the rat cardiomyocyte cell line H9C2 as an in vitro model, researchers found that hyperoxia caused cardiac hypertrophy, fibrosis, and dysfunction, alongside reduced circulating MOTS-c levels. Administration of MOTS-c was reported to markedly reduce these pathological changes and restore cardiac function in the mouse model. Mechanistically, the study found that hyperoxia activates a KEAP1–PGAM5–AIFM1 signaling axis, triggering a ROS-specific form of programmed cell death called oxeiptosis. MOTS-c appeared to interact directly with KEAP1, preserving its binding to PGAM5 and thereby preventing nuclear translocation of AIFM1, the downstream executioner of oxeiptosis. Overexpression of KEAP1 abolished MOTS-c's protective effects, supporting KEAP1 as a key target. Limitations include exclusive reliance on animal and cell-line models with no human data, a relatively narrow mechanistic focus, and the absence of long-term outcome measures. These findings are preclinical and require validation in human studies before clinical conclusions can be drawn.
Life sciences · May 2026DOI ↗ Review
This narrative review, aimed at obstetricians and gynecologists, synthesizes current evidence on GLP-1 receptor agonists (e.g., semaglutide) and dual GLP-1/GIP agonists (e.g., tirzepatide) as they relate to women's health. The authors highlight that phase 3 trials have reported 15–21% body weight reduction with these agents, with tirzepatide showing greater efficacy than semaglutide. In women with polycystic ovary syndrome (PCOS), the authors cite meta-analyses finding improvements in insulin resistance, androgen levels, and ovulation rates. Regarding contraception, the review notes that tirzepatide's gastric-emptying delay has prompted manufacturer guidance about backup contraception around initiation and dose escalation. On pregnancy safety, the authors describe emerging human cohort data suggesting no significantly increased risk of major congenital malformations from inadvertent early pregnancy exposure, while noting that animal teratogenicity data still warrant caution. Perioperative guidance has shifted toward individualized risk-stratified approaches rather than blanket discontinuation. The authors call for formal pregnancy registries to address persistent knowledge gaps. As a review, this paper does not generate new primary data, and its conclusions are limited by the underlying evidence base, which in several areas remains preliminary or indirect.
Current opinion in obstetrics & gynecology · May 2026DOI ↗ Review
This narrative review examines whether tirzepatide — a dual GIP/GLP-1 receptor agonist — may act as a disease-modifying therapy in obesity-related obstructive sleep apnea (OSA), beyond its well-established effects on weight reduction. The authors searched PubMed, Scopus, and Web of Science through January 2026, synthesizing evidence from randomized controlled trials, meta-analyses, and mechanistic studies on incretin-based therapies in obesity and OSA. The review reports that tirzepatide is associated with meaningful reductions in apnea-hypopnea index (AHI) alongside significant weight loss. Notably, the authors propose that OSA improvements may not be fully explained by weight loss alone, highlighting potential weight-independent mechanisms such as modulation of systemic inflammation, improvements in insulin sensitivity, changes in adipokine profiles, and effects on autonomic regulation and ventilatory chemosensitivity. The authors acknowledge that current evidence is insufficient to definitively separate weight-dependent from weight-independent effects, and they call for dedicated mechanistic and long-term clinical studies. A key limitation is the review's narrative — rather than systematic — design, which introduces selection bias. The paper frames tirzepatide as a potential shift from purely device-based OSA management toward integrated, pathophysiology-driven treatment strategies, but stops short of confirming disease-modifying status.
Life (Basel, Switzerland) · May 2026DOI ↗ Limited · humanPreprint
This observational cohort analysis describes weight-loss outcomes and adverse event rates in 503 overweight adults who completed six months of the "Trimsulin Weight Loss Program," a nutraceutical regimen combining two proprietary products (a powdered drink mix and a capsule) with a structured diet and exercise protocol. The authors compare their results descriptively — without inferential statistics — to published real-world data for the prescription GLP-1 receptor agonist semaglutide and the dual GIP/GLP-1 agonist tirzepatide. The study reports that Trimsulin participants experienced mean weight reductions of 7.3% at 3 months and 14.1% at 6 months, numerically exceeding the comparator figures drawn from a separate published cohort. Adverse events were self-reported by 4.8% of Trimsulin participants versus much higher rates cited for the pharmacological comparators. Key limitations are substantial: there is no randomization, no placebo or active control arm, no blinding, no direct head-to-head comparison, reliance on self-reported adverse events, a highly selected completer-only analysis (503 of 1,000+ enrollees), differing baseline BMI profiles across cohorts, and the absence of any inferential statistical testing. The program's dietary and behavioral components cannot be disentangled from any supplement effect. The authors acknowledge the need for randomized controlled trials. The paper is identified as a preprint.
Unknown journal · May 2026DOI ↗ Animal only
This study investigated an engineered variant of the mitochondria-derived peptide MOTS-c, called R13A-MOTS-c, designed to overcome the poor cellular permeability of the wild-type peptide. The researchers substituted arginine at position 13 with alanine to increase hydrophobicity, then characterized the modified peptide's uptake mechanism, showing through competition assays and knockdown experiments that it enters cells via the LAT1 amino acid transporter. In vitro, R13A-MOTS-c was reported to reduce inflammatory markers, oxidative damage, and mitochondrial dysfunction in mouse lung epithelial (MLE-12) cells exposed to radiation. In vivo, C57BL/6 mice receiving thoracic irradiation (20 Gy) and treated with intraperitoneal R13A-MOTS-c showed attenuated pulmonary inflammation, oxidative stress, and mitochondrial impairment compared to controls. The proposed mechanism centers on Nrf2 pathway activation, supported by evidence of increased nuclear Nrf2 translocation and upregulation of downstream target genes; protective effects were lost when LAT1 or Nrf2 was inhibited or knocked out. Key limitations include exclusive use of animal and cell models with no human data, a single radiation dose and treatment regimen tested, and the need for further pharmacokinetic and safety characterization before clinical translation.
Redox biology · May 2026DOI ↗ 🧪 TrialInsufficient
Registered Phase 3 interventional trial (recruiting). Efficacy, safety and tolerability of switching from GLP-1RA to maridebart cafraglutide in adults with obesity or overweight.
ClinicalTrials.gov · May 2026View trial ↗ Limited · human
This case series describes two patients with severe obesity who developed moderate-to-severe cutaneous allodynia — a condition where normally non-painful stimuli such as touch or mild temperature change cause pain — while being treated with the dual GLP-1/GIP receptor agonist tirzepatide for weight management. In both cases, the onset of allodynia was temporally linked to dose escalation, occurring at higher doses, and resolved upon discontinuation of the drug. The allodynia varied between static and dynamic types across the two patients. The authors reviewed the tirzepatide U.S. prescribing information and found no prior documentation of skin pain or allodynia as an adverse event, though a prior FDA Adverse Event Reporting System (FAERS) pharmacovigilance analysis had identified rare allodynia signals across six GLP-1RAs. The authors assert this is the first case series specifically reporting allodynia with tirzepatide. Key limitations include the very small sample size (n=2), absence of a control group, and the inherent inability to establish causality from case reports alone. The temporal association and resolution upon drug withdrawal do, however, provide a suggestive signal warranting further investigation.
The American journal of case reports · May 2026DOI ↗ Review
This narrative review evaluates whether incretin-based therapies — specifically GLP-1 receptor agonists (e.g., semaglutide) and dual GLP-1/GIP receptor agonists (e.g., tirzepatide) — warrant consideration as first-line antihypertensive agents. The authors synthesize findings from recent large-scale trials demonstrating that these agents are associated with significant reductions in body weight, blood pressure, and adverse cardiovascular outcomes. Mediation analyses cited in the review suggest that weight loss accounts for a substantial portion of the observed blood pressure reductions; however, the authors also highlight putative direct mechanisms, including improvements in vascular function, renal sodium handling, and neurohumoral pathway modulation. The review notes that beneficial effects on blood pressure appear consistent across diverse patient populations, including those without established hypertension. A key limitation acknowledged by the authors is the absence of randomized controlled trials specifically designed with blood pressure as a primary endpoint. Based on the available evidence, the authors conclude that incretin-based therapies may have an emerging role in hypertension management guidelines, particularly for selected high-risk populations. As a review article, conclusions are dependent on the quality and interpretation of the underlying primary studies cited.
Current hypertension reports · May 2026DOI ↗