Limited · human
This pharmacovigilance study examined safety signals associated with potentially counterfeit semaglutide products by conducting a descriptive and disproportionality analysis of Individual Case Safety Reports (ICSRs) submitted to the European pharmacovigilance database EudraVigilance between January 2018 and December 2025. Researchers identified 234 ICSRs linked to suspected counterfeit semaglutide, of which 73.5% involved female patients and 35.5% involved adults. Notably, 89.3% of reported suspected adverse drug reactions (ADRs) were classified as serious. The most commonly reported suspected ADRs were vomiting, nausea, and hypoglycemia. Disproportionality analysis revealed a statistically higher reporting frequency for hypoglycemia, product use in an unapproved indication, malaise, and drug ineffectiveness compared with reports involving non-counterfeit semaglutide. The authors suggest these signals may reflect contamination, incorrect active ingredients, or subtherapeutic dosing in counterfeit products. Limitations include the inherent biases of spontaneous pharmacovigilance reporting (underreporting, lack of denominator data, and inability to confirm causality), reliance on database classifications of "counterfeit," and the descriptive nature of the analysis. The study concludes that pharmacovigilance databases can play a useful role in detecting safety concerns related to counterfeit medicines, and calls for further research.
Frontiers in pharmacology · Apr 2026DOI ↗ Limited · humanPreprint
This prospective cohort study investigated whether adjunctive thymosin alpha 1 (Thα1) combined with intravenous immunoglobulin (IVIG), initiated 8–10 days after rituximab, could reduce pulmonary adverse events (PAEs) in 379 patients with B-cell lymphoma (BCL) receiving R-CHOP chemotherapy. Patients were assigned to either standard R-CHOP alone (n=164) or R-CHOP plus Thα1-IVIG (n=215); the study was conducted over approximately 11 years. The study found that the Thα1-IVIG group had a notably lower rate of overall PAEs (13.0% vs. 31.7%), with reductions in both infectious pulmonary events and interstitial pulmonary disease. Five-year event-free survival also appeared to favor the adjunctive group. Multivariable Cox proportional hazards models were used to identify independent risk and protective factors. Key limitations include the non-randomized, observational design (patients were not randomly assigned), potential for selection bias and confounding, the preprint status of the manuscript (not yet peer-reviewed), the single-study nature of the findings, and the lack of blinding. These factors substantially limit causal interpretation of the results, and findings should be considered hypothesis-generating pending confirmatory randomized controlled trials.
Unknown journal · Apr 2026DOI ↗ Limited · humanPreprint
This bioinformatics study investigated the role of melatonin-related genes in coronary heart disease (CHD) by analyzing two publicly available gene expression datasets (GSE179789 and GSE113079). Using differential expression analysis and validation, the researchers identified two genes—MAP2K2 (a mitogen-activated protein kinase kinase) and PGD (phosphogluconate dehydrogenase)—as candidate CHD biomarkers, both showing significant upregulation in CHD samples across both datasets. Gene set enrichment analysis (GSEA) linked these genes to pathways including ribosome function, prion diseases, and Parkinson's disease. The study also mapped complex regulatory networks involving lncRNAs, miRNAs, and transcription factors; notably, four lncRNAs (NEAT1, AP000766.1, LINC02381, and XIST) were found to regulate PGD via hsa-let-7e-5p, and 29 transcription factors co-regulated both biomarkers. Drug-target network analysis predicted 41 drugs targeting MAP2K2 and 3 targeting PGD. Biomarker expression was further validated in clinical samples via RT-qPCR. Limitations include the observational and computational nature of the study, reliance on public datasets, small clinical validation cohorts typical of such designs, and the absence of functional or mechanistic experiments confirming causal roles. The study is reported as a preprint and has not undergone formal peer review.
Unknown journal · Apr 2026DOI ↗ Limited · human
This large-scale observational study used a federated biomedical data platform to analyze 135,349 individuals treated with GLP-1 receptor agonists (GLP-1RAs) — specifically semaglutide (Wegovy) and tirzepatide (Zepbound) formulations — to characterize differences between "super responders" (>15% weight loss), "moderate responders" (5–15% weight loss), and a "minimal weight-loss" group. The study found substantial heterogeneity in weight-loss outcomes across patients receiving the same therapies. Notably, super responders to Zepbound showed reduced risk of developing certain comorbidities, including conditions at relative risks as favorable as 0.5 for osteoarthritis (P = .001), while Wegovy super responders showed an association with psoriasis (RR = 2.5, P = .03). The authors conclude that differences in weight trajectories likely reflect a combination of biological, behavioral, and social factors. Key limitations include the observational, retrospective design (which cannot establish causation), the reliance on federated real-world data (subject to coding variability), and lack of randomization. The authors call for prospective studies to develop more individualized weight-loss strategies.
Biology methods & protocols · Apr 2026DOI ↗ Limited · human
This real-world observational study examined weight trajectories in 4,182 patients during the 6 months following their last documented semaglutide or tirzepatide prescription, drawn from a federated health network. The study found that approximately two-thirds of the full cohort showed stable weight or continued weight loss after their final prescription. In a representative subset of 300 patients whose clinical notes were analyzed using a large language model (LLM), treatment discontinuation was confirmed in 119 patients (40%), and of those, 72% did not demonstrate weight regain. The study also noted that exercise counseling was documented more frequently among patients who maintained weight loss compared to those who experienced weight regain (26.2% vs. 14.7%; P = .04). Key limitations include the observational and retrospective design, reliance on documented prescriptions rather than confirmed medication use, potential incompleteness of clinical records, use of an LLM for data curation introducing possible inaccuracies, and the inability to establish causation. The authors acknowledge that further studies are needed to understand the mechanisms behind these real-world patterns of weight maintenance after GLP-1 receptor agonist discontinuation.
Biology methods & protocols · Apr 2026DOI ↗ Limited · human
This cross-sectional study investigated the relationship between serum levels of MOTS-c — a mitochondria-derived peptide encoded in the 12S rRNA — and myocardial ischemia-reperfusion injury (MIRI) in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). Seventy-two AMI patients were divided into MIRI (n=34) and non-MIRI (n=38) groups. The study measured MOTS-c concentrations in both peripheral serum and intracoronary blood, alongside clinical variables. The MIRI group displayed lower systolic blood pressure, lower pre-operative TIMI grade, and lower HDL-C, while showing higher total ischemic time, door-to-balloon time, culprit vessel stenosis severity, Killip grade, and adverse event rates. Multivariate logistic regression identified postoperative peripheral serum MOTS-c as an independent protective factor against MIRI, and ROC analysis suggested potential predictive value for MIRI. Limitations include the small sample size, single-center cross-sectional design, lack of causal inference, and the absence of dynamic longitudinal monitoring of MOTS-c. The authors conclude that MOTS-c warrants further investigation as a novel biomarker and potential therapeutic target for MIRI, pending validation in larger prospective studies.
Biomedicines · Apr 2026DOI ↗ Limited · human
This review-style report examines the transfer of tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, into human breastmilk following subcutaneous administration. The paper notes that tirzepatide is generally undetectable in breastmilk at doses up to 5 mg, suggesting minimal maternal-to-infant transfer via lactation. The authors further reason that even if trace amounts were present, oral absorption by a nursing infant would likely be negligible, as the peptide is expected to undergo partial degradation in the infant's gastrointestinal tract and exhibits poor oral bioavailability. Based on these considerations, the paper concludes that maternal use of tirzepatide need not be an automatic reason to discontinue breastfeeding, while still recommending caution — particularly in the context of newborns or preterm infants, whose gastrointestinal and metabolic systems may differ from those of older infants. The report acknowledges that available data remain limited and calls for additional research before stronger conclusions can be drawn. Key limitations include the small body of evidence underpinning these conclusions and the absence of robust clinical trial data in lactating populations.
Unknown journal · Apr 2026Source ↗ Limited · human
This multicenter retrospective cohort study used the TriNetX database to examine whether preoperative exposure to GLP-1 receptor agonists (GLP-1 RAs) was associated with postoperative GLP-1 RA use following metabolic bariatric surgery (MBS). Researchers identified adults who underwent MBS and applied 1:1 propensity score matching to compare those with and without preoperative GLP-1 RA exposure (n = 2,811 per group). The study found that patients with prior GLP-1 RA exposure had more than twice the rate of postoperative GLP-1 RA initiation (15.3% vs. 7.6%; HR: 2.14, 95% CI: 1.81–2.52). The exposure group also showed a modestly higher prevalence of suboptimal weight control post-surgery (HR: 1.18), though rates of suboptimal glycemic control, hospitalization, and emergency department visits did not differ significantly between groups. These patterns were consistent across surgical subtypes and age groups. The authors interpret the findings as identifying a distinct patient phenotype with greater treatment complexity rather than a direct causal relationship. Key limitations include the retrospective design, reliance on a claims-based database, and potential residual confounding despite propensity score matching.
Obesity surgery · Apr 2026DOI ↗ Limited · human
This systematic review examined the effects of GLP-1 receptor agonists (GLP-1 RAs) on patients with hidradenitis suppurativa (HS), a chronic, painful inflammatory skin condition often associated with obesity and metabolic syndrome. Researchers searched Embase and PubMed, screening 300 papers and ultimately including 10 studies in the final analysis. The review found that HS patients using GLP-1 RAs tended to experience improvements in clinical course, including reductions in pain and suppuration, as well as improvements in quality of life and mental health. Cardiovascular risk markers also appeared to improve. Notably, inflammatory laboratory parameters did not show statistically significant changes. Higher drug doses were more frequently associated with clinical improvement, while reductions in weight or BMI did not consistently correlate with improvements in Hurley staging, pain, or depression scores. The authors suggest this raises the possibility that GLP-1 RAs may act through direct anti-inflammatory mechanisms beyond weight loss alone, though they acknowledge this remains unresolved. Key limitations include the small number of included studies (10), likely heterogeneous study designs across the included papers, and the inability to establish causality or rule out confounding. The authors call for further dedicated studies to clarify the mechanism of benefit.
Journal of clinical medicine · Apr 2026DOI ↗ Limited · human
This observational case-control study investigated whether serum MOTS-c levels and the mitochondrial m.1382A>C gene polymorphism are associated with polycystic ovary syndrome (PCOS) in adolescents. A total of 246 participants aged 12–18 were enrolled: 121 diagnosed with PCOS (based on irregular menstrual cycles and clinical/biochemical hyperandrogenism) and 125 healthy controls with regular menstruation. Serum MOTS-c levels were measured by ELISA, and the m.1382A>C polymorphism was assessed by gene sequencing. The study found that mean serum MOTS-c levels were slightly higher in the PCOS group compared to controls, but this difference did not reach statistical significance (p = 0.059). No significant associations were observed between MOTS-c levels and anthropometric or metabolic parameters within the PCOS group. Notably, all participants carried the wild-type (A/A) genotype for the m.1382A>C polymorphism, making genetic association analysis impossible in this cohort. The authors concluded that MOTS-c may play only a minor role in PCOS pathophysiology. Limitations include the modest sample size, the adolescent-only population, the absence of polymorphism variability, and the cross-sectional design precluding causal inference.
Archives of endocrinology and metabolism · Apr 2026DOI ↗ Limited · human
This cross-sectional study conducted in Saudi Arabia (January–June 2025) investigated the frequency, characteristics, and predictors of hair loss among 254 adults using GLP-1 receptor agonists (GLP-1RAs) — specifically semaglutide (Ozempic), tirzepatide (Mounjaro), liraglutide (Saxenda), or liraglutide (Victoza) — primarily for weight loss. Data were collected via structured questionnaires covering demographics, clinical characteristics, and hair loss details such as timing, severity, and progression. The majority of participants were female (71.3%), with a mean age of approximately 33 years. The study found that overall hair loss prevalence did not differ significantly across GLP-1RA types (p = 0.116); however, severe hair loss was reported significantly more often among Mounjaro (43.4%) and Saxenda (42.9%) users. Female sex and Mounjaro use were identified as notable predictors of hair loss. The authors noted that the hair loss observed was generally non-scarring and potentially reversible, but associated with psychological distress and possible impacts on treatment adherence. Key limitations include the cross-sectional design (precluding causal inference), reliance on self-reported data, the single-country sample limiting generalizability, and the absence of a control group not using GLP-1RAs.
Journal of cosmetic dermatology · Apr 2026DOI ↗ Limited · human
This study investigated the role of MOTS-c, a mitochondrially encoded regulatory peptide, in protecting spermatogenesis. Researchers first measured serum MOTS-c levels in patients with oligoasthenozoospermia (a condition involving reduced and poorly motile sperm), finding these levels were significantly lower than in fertile controls and correlated positively with semen quality parameters. To model spermatogenic dysfunction mechanistically, the researchers used a microgravity-based mechanical stress model in mice, which induced decreased sperm concentration, disrupted seminiferous tubule architecture, and reduced spermatogonia counts. Exogenous MOTS-c administration was shown to ameliorate these impairments by suppressing oxidative stress and ferroptosis — a form of iron-dependent programmed cell death. The study identified SLC7A11 (Solute Carrier Family 7 Member 11), a known ferroptosis regulator, as a molecular target of MOTS-c. Loss- and gain-of-function experiments confirmed that SLC7A11 inhibits ferroptosis and oxidative stress while promoting spermatogonia proliferation. MOTS-c's protective effects were shown to depend, at least in part, on upregulating SLC7A11 under mechanical stress conditions. Limitations include the small and uncharacterized human cohort, reliance on an indirect mechanical stress model, and predominantly animal/cellular mechanistic data.
Free radical biology & medicine · Mar 2026DOI ↗ Limited · human
This case report describes a 54-year-old male who presented to the emergency department with acute left upper quadrant pain and vomiting, and was found to have atraumatic splenic rupture (ASR) — a rare, potentially fatal condition. The patient had recently been using two performance-enhancing compounds: MK-677 (ibutamoren), a growth hormone secretagogue, and RAD-140 (testolone), a selective androgen receptor modulator (SARM). CT imaging confirmed a large perisplenic hematoma. Initial management with splenic artery embolization provided only transient stabilization, and the patient ultimately required emergency laparotomy with total splenectomy. Histopathology revealed extensive splenic infarction and features suggestive of an underlying vascular malformation. The authors speculate — without establishing causation — that the pharmacological effects of RAD-140 and MK-677 on androgen receptor signalling and IGF-1 pathways may have contributed to splenic complications, drawing an analogy to the known association between anabolic steroids and peliosis. No prior literature directly links these compounds to splenic pathology. The report highlights the importance of prompt diagnosis and surgical management of ASR. Key limitations include the single-patient design, inability to confirm causality, and presence of a potential pre-existing vascular malformation as a confounding factor.
Limited · human
This pharmacovigilance study compared post-marketing adverse event reporting patterns for tirzepatide (a dual GIP/GLP-1 receptor agonist) against semaglutide and liraglutide (GLP-1 receptor agonists) using aggregated Individual Case Safety Reports (ICSRs) from the EudraVigilance database. Researchers applied pairwise disproportionality analyses using reporting odds ratios (RORs) at the System Organ Class (SOC) level, with false discovery rate correction and sensitivity analyses limited to serious and healthcare professional-reported cases. The study found that, compared with semaglutide, tirzepatide was associated with higher relative reporting for immune system disorders (ROR 1.97) and hepatobiliary disorders (ROR 1.71). Compared with liraglutide, tirzepatide showed higher reporting for musculoskeletal (ROR 2.02) and psychiatric disorders (ROR 2.14), but lower reporting for neoplasms (ROR 0.28). Eight SOCs remained significant across all analytical conditions. The authors emphasize that these findings are hypothesis-generating only, as disproportionality analyses cannot establish causality, do not adjust for exposure levels, and are subject to reporting biases inherent in spontaneous pharmacovigilance databases. Confirmation in exposure-adjusted studies is recommended.
International journal of molecular sciences · Mar 2026DOI ↗ Limited · human
This study characterizes PG-102, a bispecific Fc fusion protein that co-activates both GLP-1 and GLP-2 receptors, combining preclinical animal work with a Phase I human trial. In db/db mice (a model of advanced type 2 diabetes with hyperglycemia and catabolic weight loss), PG-102 demonstrated superior and more sustained glycemic control compared to semaglutide or tirzepatide while preserving body weight — an effect attributed to β-cell preservation and enhanced glucose uptake rather than acute insulin stimulation. Mechanistic experiments suggested that dual receptor engagement was necessary for these benefits, with PG-102 also promoting coordinated, delayed receptor internalization compared to monospecific agents. The Phase I randomized, double-blind, placebo-controlled trial enrolled 24 adults with overweight (BMI 25–30 kg/m²) across three dose cohorts, with 18 receiving PG-102 and 6 receiving placebo. The primary endpoint was safety and tolerability. Treatment-emergent adverse events occurred in 83.3% of PG-102 participants and 66.7% of placebo participants; gastrointestinal events were mild to moderate. No serious adverse events or treatment discontinuations were reported. Limitations include the small sample size, single-center design, overweight-only population, and lack of efficacy endpoints in the human portion of the study.
Nature communications · Mar 2026DOI ↗ Limited · human
This pharmacovigilance study analyzed ocular adverse event (AE) reports associated with five GLP-1 receptor agonists (exenatide, tirzepatide, dulaglutide, liraglutide, and semaglutide) using the FDA Adverse Event Reporting System (FAERS) from 2005 to 2024. Ocular AEs comprised 3.61% of all GLP-1 RA-related reports; the median patient age was 63 years, and 62.6% of reports involved female patients. Disproportionality analysis using reporting odds ratios (RORs) identified a statistically significant signal for ocular AEs associated with semaglutide, while exenatide showed a significant annual decline in proportional reporting (-5.15% per year). The authors note that semaglutide's signal may partly reflect its growing market dominance rather than a true differential risk. Key limitations acknowledged by the study include the absence of exposure denominators and comparator groups, vulnerability of FAERS to reporting bias (including under- and over-reporting), and inability to establish causality. The authors characterize the findings as hypothesis-generating and recommend clinician vigilance regarding ocular monitoring, particularly in populations already at elevated risk for diabetic eye disease, while calling for further prospective research to validate these associations and explore potential mechanisms.
Journal of clinical medicine · Mar 2026DOI ↗ Limited · human
This Brazilian retrospective regulatory surveillance study examined patterns of GLP-1 receptor agonist (GLP-1 RA) consumption, pharmacovigilance reports, and product falsification alerts between 2020 and 2024. Researchers triangulated data from three official sources: national pharmaceutical sales records classified by the Anatomical Therapeutic Chemical (ATC) system, adverse event reports submitted to Vigimed (Brazil's national pharmacovigilance platform linked to the global VigiBase), and official counterfeit product alerts. The study found that semaglutide was the dominant GLP-1 RA in the Brazilian market. Consumption was heavily concentrated in higher-GDP regions, revealing a geographic and economic disparity that did not align with regional diabetes prevalence rates. Pharmacovigilance data revealed a notable proportion of reports associated with off-label use, suggesting potential gaps in clinical practice and regulatory oversight. Additionally, documented cases of counterfeit GLP-1 RA products highlighted supply chain vulnerabilities. The authors concluded that rising demand, widespread off-label use, and product falsification collectively require a coordinated regulatory response. Limitations include the retrospective and observational nature of the data, reliance on administrative and surveillance databases, and the potential for underreporting in pharmacovigilance systems.
Diabetes, obesity & metabolism · Mar 2026DOI ↗ Limited · human
This Austrian real-world study examined afamelanotide treatment outcomes in 20 patients with erythropoietic protoporphyria (EPP), a rare genetic disorder causing severe phototoxic reactions upon light exposure. Researchers compared pre- and post-treatment data on quality of life (QoL), phototoxic burn tolerance time (PBTT), UV index, and the incidence and severity of phototoxic reactions for the year 2023. The study found that the EPP-specific QoL score increased markedly, with the median rising from 11.11 to 79.17 under therapy. PBTT also improved substantially, increasing from a median of 15 minutes before treatment to 250 minutes during treatment. The proportion of patients experiencing phototoxic reactions fell from 88% at baseline to 33% on therapy. Reported side effects were described as only mild and transient. The authors concluded that these findings support the effectiveness and safety of afamelanotide in EPP. Limitations include the small sample size (n=20), the non-randomized, uncontrolled observational design, and the potential for recall or reporting bias inherent to real-world cohort studies.
Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG · Mar 2026DOI ↗ Limited · human
This retrospective observational study analyzed data from the National Poison Data System (NPDS) to characterize and compare glucagon-like peptide-1 receptor agonist (GLP-1 RA) exposures reported to U.S. poison centers between 2017 and 2024, focusing on differences between children (ages 6–17) and adults. Across 13,924 single-substance GLP-1 RA exposures, the authors found a dramatic overall increase of 1,830.8% in exposure rates over the study period, with an even steeper 4,805.0% rise among children 6–17 years old, most of which occurred after 2021. The majority of exposures (91.7%) resulted in no or mild effects; however, moderate effects were seen in 8.0% of cases and major effects in 42 exposures, with two deaths recorded. Children aged 6–17 were significantly more likely to be hospitalized than adults (RR: 2.66), and adolescents aged 12–17 were more likely to experience a serious medical outcome (RR: 1.68). Vomiting was the most common clinical effect in children (88.2%) versus adults (61.3%). Notably, exposures among children were far more likely to be classified as intentional misuse compared to adults (RR: 8.12). Limitations include reliance on voluntarily reported poison center data, potential underreporting, and inability to establish causation.
Journal of medical toxicology : official journal of the American College of Medical Toxicology · Mar 2026DOI ↗ Limited · human
This qualitative, multi-method study explored how adults living with obesity make decisions about initiating pharmacotherapy. Researchers used three complementary methods — semi-structured interviews (n=15), a Photovoice study (n=12), and focus group discussions (n=12) — to purposively recruit adults aged 18–70 with a BMI ≥27 kg/m² and at least one obesity-related complication, all of whom were naïve to obesity medications. Through triangulation of findings across all three methods, the study identified five key factors shaping patient preferences: (1) anticipated treatment efficacy, (2) adequacy of information and community support, (3) safety and tolerability profile, (4) treatment burden and lifestyle integration, and (5) logistical and structural barriers. Tirzepatide was the most preferred agent across all methods, largely due to its perceived weight-reduction potential, while semaglutide ranked second, aided by its broader societal familiarity. Perceived efficacy and information trustworthiness emerged as the dominant drivers of preference, with safety concerns consistently moderating enthusiasm. The study is limited by its qualitative design, modest sample sizes, and the fact that all participants were medication-naïve, which may limit transferability to experienced patients. The authors recommend clinicians engage in shared decision-making tailored to individual information needs and social contexts.
Obesity pillars · Mar 2026DOI ↗