In vitro
This study reports the first-in-class design of unimolecular "tetra-agonists" — single peptide molecules engineered to simultaneously activate four metabolically relevant receptors: GLP-1R, GIPR, GcgR (all class B GPCRs), and Y2R (a class A GPCR). Prior work had yielded dual and triple agonists exploiting sequence homology among class B GPCR ligands, but incorporating Y2R agonism was considered a major challenge due to the structural and sequence divergence between class A and class B GPCRs. The researchers used rational chimeric peptide design to overcome these topological constraints, producing high-potency tetra-agonists. They further showed that lipidation of the scaffold was well tolerated, potentially improving therapeutic viability. The study also explored biased agonism at GLP-1R, demonstrating that cAMP signaling could be selectively amplified while minimizing β-arrestin recruitment — a mechanism that may reduce receptor desensitization. A tunable framework for modulating β-arrestin engagement without compromising cAMP potency is also described. Limitations include that all experiments appear to be conducted in vitro (cell-based receptor activation and signaling assays), with no animal or human efficacy data reported. The work is primarily a molecular pharmacology and peptide chemistry study establishing proof-of-concept at the receptor level.
Journal of the American Chemical Society · Jun 2025DOI ↗ Animal only
This study investigated whether the synthetic hexapeptide Growth Hormone-Releasing Peptide-6 (GHRP-6), a ghrelin analog with known growth-promoting and immunomodulatory properties in fish, could protect against Nervous Necrosis Virus (NNV) — a pathogen that damages the central nervous system of many commercially farmed fish species. The researchers used two complementary approaches. In vitro, E11 fish cell lines were treated with GHRP-6 before and/or during NNV infection; treated cells showed higher survival rates, reduced viral genome replication, and lower production of infective viral particles compared to untreated controls. In vivo, European seabass (Dicentrarchus labrax) were given intraperitoneal injections of GHRP-6, which led to significant upregulation of immune-related genes — including TNF-α, RTP3, and IgM — in the head kidney and intestine. NNV replication in the brain was also lower in GHRP-6-treated fish than in controls, and the brain's antiviral immune response was modulated. The authors conclude that GHRP-6 shows potential as an antiviral agent for aquaculture disease prevention. Key limitations include that all experiments were conducted in fish (not humans) and the in vivo work lacked a full challenge trial design.
Aquaculture international · Jun 2025
Limited · human
This 6-month phase 2 randomized open-label clinical trial investigated whether tesamorelin, a growth hormone-releasing hormone analog, could improve neurocognitive impairment (NCI) in people with HIV who were virally suppressed on antiretroviral therapy and had abdominal obesity (elevated waist circumference). Seventy-three participants were randomized 3:2 to tesamorelin or standard of care (SOC). The primary outcome was change in neurocognitive performance at 6 months; secondary outcomes included waist circumference, mood, and daily functioning. The tesamorelin group showed a non-significant trend toward improved neurocognitive performance (mean change 0.146; P=.060), while the SOC group did not improve (P=.295); crucially, the between-group difference was not statistically significant (P=.673). Tesamorelin did produce a significantly greater reduction in waist circumference versus SOC (median difference −2.7 cm; P=.015). IGF-1 levels rose in the tesamorelin group but did not correlate with cognitive or waist circumference changes. Key limitations include an open-label (non-placebo-controlled) design, modest sample size resulting in insufficient statistical power, and the relatively short 6-month follow-up. The authors concluded there was no clear cognitive benefit from short-term abdominal obesity reduction with tesamorelin in this population.
The Journal of infectious diseases · Jun 2025DOI ↗ Limited · humanPreprint
This observational study examined the relationship between salivary oxidized forms of thymosin β4 (Tβ4) and thymosin β10 (Tβ10) and oxidative stress-related diseases in preterm infants born before 30 weeks of gestation. Researchers collected 149 saliva samples from 18 infants and analyzed the intact salivary proteome using nano-HPLC-ESI-MS, with relative quantification based on extracted ion current (XIC) peak area. The study found that post-menstrual age correlated significantly with total Tβ4, oxidized Tβ4 percentage, and total Tβ10. Higher fraction of inspired oxygen (FiO₂) values were associated with lower levels and percentages of oxidized Tβ10. Thymosin levels did not differ between infants with or without retinopathy of prematurity; however, higher oxidized Tβ10 levels were observed in infants who did not develop bronchopulmonary dysplasia (BPD), leading the authors to suggest a possible protective role for oxidized Tβ10 in inflammation and tissue repair. Key limitations include the very small sample size (18 infants), observational design, and the inability to establish causality. The authors propose saliva as a non-invasive matrix for future monitoring of oxidative stress in neonates.
Unknown journal · May 2025DOI ↗ Strong · human
The GLORY-1 trial was a phase 3, randomized, double-blind, placebo-controlled study conducted in China evaluating mazdutide — a once-weekly injectable glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist — for weight management in adults with overweight or obesity. A total of 610 participants (mean BMI 31.1, mean body weight 87.2 kg) were randomly assigned 1:1:1 to receive one of two doses of mazdutide or placebo for 48 weeks. The two co-primary endpoints at week 32 were percent change in body weight and the proportion achieving at least 5% weight reduction, analyzed using a treatment-policy estimand. The study found that both mazdutide groups achieved statistically significant and clinically meaningful reductions in body weight compared to placebo at week 32, with the higher dose group achieving a greater mean reduction than the lower dose group; the placebo group had a marginal mean weight gain. The proportions achieving ≥5% weight loss were substantially higher in both active treatment groups versus placebo. Limitations include the single-country (China) design, limiting generalizability, and the 32-week primary endpoint in a 48-week trial. Safety data were not detailed in the abstract.
The New England journal of medicine · May 2025DOI ↗ 🧪 TrialInsufficient
Registered Phase 1 interventional trial (completed). The purpose of this study is to measure the effect of retatrutide versus placebo, administered every week, on time to recovery from hypoglycemia during hypoglycemic clamp in participants with Type 2 Diabetes Mellitus (T2DM) following 16 weeks of treatment.
ClinicalTrials.gov · May 2025View trial ↗ Review
This review examines metabolic dysfunction-associated steatotic liver disease (MASLD) as it specifically affects people with HIV (PWH). The authors highlight that MASLD is highly prevalent in this population and follows a more aggressive clinical course than in HIV-negative individuals. The review discusses how HIV-specific factors — including altered body composition, chronic immune activation, enhanced gut permeability, and antiretroviral therapy (ART) side effects — compound the common pathogenic mechanisms of MASLD, accelerating disease progression. The authors note the recent adoption of updated MASLD nomenclature and the first FDA-approved MASLD therapy, emphasizing that these advances have not yet been adequately studied in PWH. They identify a critical evidence gap in evaluating emerging MASLD therapies specifically within this population. Among interventions studied in PWH, the review highlights early promise from glucagon-like peptide-1 (GLP-1) receptor agonists and the growth hormone-releasing hormone analog tesamorelin. The authors conclude that MASLD is a meaningful driver of both liver-related and cardiovascular morbidity in PWH, and that the distinct pathophysiology of MASLD-HIV necessitates tailored diagnostic and management strategies. Limitations include the review format and the scarcity of dedicated clinical trial data in PWH.
Current opinion in HIV and AIDS · May 2025DOI ↗ 🧪 TrialInsufficient
Registered Phase 1 interventional trial (recruiting). The primary objective of Study GZQG is to compare the effect of retatrutide and placebo on total clamp disposition index (cDI) after 28 weeks of treatment.
ClinicalTrials.gov · May 2025View trial ↗ Limited · human
This cross-sectional study examined self-reported outcomes among 486 adults in Kuwait who were using or had previously used GLP-1 receptor agonist (GLP-1 RA) injections — Semaglutide (n=181), Liraglutide (n=152), or Tirzepatide (n=132) — for weight loss, surveyed between February and May 2024. Participants completed an online questionnaire covering demographics, weight change, side effects, and quality of life. The study found that Tirzepatide users reported the highest average monthly and annual weight loss, along with the greatest satisfaction (88%) and most frequently reported improvements in quality of life (60%) compared to the other two agents. Side-effect profiles differed across groups: Tirzepatide users more commonly reported belching, while Liraglutide users reported higher rates of anxiety and were more likely to switch medications. No statistically significant differences were observed between groups in BMI, dietary adherence, or treatment compliance. Key limitations include the cross-sectional, self-report design, recruitment via online survey (introducing selection bias), lack of clinical verification of outcomes, and the inability to establish causality. The study also does not account for differences in duration of use, dosing, or baseline characteristics across groups.
Frontiers in nutrition · May 2025DOI ↗ 🧪 TrialInsufficient
Registered Phase 4 interventional trial (not yet recruiting). The rapid emergence of new and highly effective obesity medications has turned the field of pediatric weight management on its head. Adolescents living with obesity, their caregivers, healthcare providers, healthcare systems, policymakers, and payors are now wondering what role health behavior and lifestyle treatment (HBLT) has in terms of body mass index (BMI) reduction, improvements in quality of life and cardiometabolic health, and mitigating nutritional concerns when medications are used. Is intensive HBLT needed or could low in
ClinicalTrials.gov · May 2025View trial ↗ 🧪 TrialInsufficient
Registered Phase 2 interventional trial (recruiting). The purpose of this research study is to evaluate what type of treatment will be beneficial for people with Crohn's disease and difficult to treat inflammation in the small bowel. Current therapies are used to control the inflammation due to Crohn's disease in your digestive tract. In some patients, those therapies are not sufficient to fully treat the disease. This objective of this study is to evaluate the efficacy of a different type of therapy, tirzepatide, that may promote healing of the affected intestinal segment. To evaluate the eff
ClinicalTrials.gov · May 2025View trial ↗ Insufficient
This paper presents the protocol for PANDA II, a multicenter randomized controlled trial investigating whether thymosin alpha 1 (Tα1) supplementation can prevent organ dysfunction following acute type A aortic dissection (ATAAD) surgical repair. A total of 330 patients will be equally randomized to receive either Tα1 plus standard care or placebo plus standard care. The primary endpoint is the difference in mean postoperative Sequential Organ Failure Assessment (SOFA) scores measured daily through postoperative day 7. The scientific rationale centers on Tα1's proposed ability to rebalance post-operative immune dysregulation, thereby reducing systemic inflammatory response syndrome (SIRS)-mediated organ injury. As a protocol paper, no efficacy or outcome data are yet available. Limitations inherent to this stage include the absence of results, potential challenges in blinding given Tα1's immunological activity, and the complexity of standardizing post-surgical care across multiple centers. The trial is registered on ClinicalTrials.gov (NCT05339529). Findings will be published once the trial is completed, and this protocol represents a foundational step toward establishing evidence for Tα1 as a novel therapeutic strategy in this high-risk surgical population.
Future cardiology · May 2025DOI ↗ Moderate · human
This systematic review and meta-analysis compared the weight-loss effectiveness of tirzepatide versus semaglutide in humans by searching PubMed, Scopus, and Web of Science through January 2025. From 751 initial records, seven studies were ultimately included — two randomized controlled trials (RCTs) and five retrospective cohort studies. Using a random-effects model in RStudio, the authors pooled mean differences (MDs) in body weight change between the two agents. The analysis found that tirzepatide was associated with statistically significantly greater weight loss compared to semaglutide (MD = 4.23 kg; 95% CI: 3.22–5.25). Subgroup analyses suggested that higher tirzepatide doses (>10 mg) and longer treatment durations (>6 months) were associated with progressively larger weight differences. Study quality was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias version 2 tool for RCTs; the authors reported high quality and low risk of bias overall. Publication bias was evaluated via forest plots and Egger's test. Limitations include the small number of included studies (only two RCTs), reliance on retrospective real-world data for most of the analysis, potential heterogeneity across study populations, and the possibility of residual confounding in the observational studies.
Journal of clinical medicine research · May 2025DOI ↗ Limited · human
This retrospective pharmacovigilance study examined whether specific drugs are disproportionately associated with carpal tunnel syndrome (CTS) reports in the FDA Adverse Event Reporting System (FAERS) database between October 2003 and September 2024. Using OpenVigil 2.1, researchers applied disproportionality analysis—primarily reporting odds ratios (RORs)—supplemented by Bayesian confidence propagation neural network algorithms to identify significant drug-CTS signals. Out of nearly 13 million adverse event reports, 6,837 (0.05%) involved CTS, with female patients comprising 69.5% of cases and a mean age of 57 years. Ten drugs showed strong, statistically significant associations with CTS reports: enzyme replacement therapies (idursulfase, galsulfase, laronidase), the growth hormone-releasing factor analog tesamorelin, the aromatase inhibitor anastrozole, bisphosphonates (alendronic acid, alendronate), gamma-hydroxybutyric acid (GHB), the COX-2 inhibitor rofecoxib, and the transthyretin stabilizer tafamidis. The study's key limitations include its reliance on spontaneous reports (subject to underreporting, reporting bias, and confounding), an inability to establish causality, and lack of exposure-denominator data. The authors conclude that clinicians should be alert to CTS symptoms in patients prescribed these medications.
Review
This review examines amylin, a neuroendocrine hormone co-secreted with insulin, exploring its physiological mechanisms and therapeutic potential in diabetes and obesity. The authors describe how amylin suppresses glucagon secretion, delays gastric emptying, increases energy expenditure, and promotes satiety — making it a candidate for addressing multi-hormonal dysregulation in both type 1 and type 2 diabetes. The paper notes that amylin is deficient in people with diabetes and that pramlintide, currently the only approved amylin analog, has shown efficacy in improving postprandial and overall glycemic control without increasing hypoglycemia risk or promoting weight gain in people with advanced β-cell dysfunction. The authors also discuss barriers to broader clinical translation, including complex receptor biology, amyloidogenic properties, and pharmacokinetic challenges. Emerging strategies covered include PEGylation, carbohydrate conjugation, oral formulations, and combination therapies — notably CagriSema, a co-formulation of a GLP-1 receptor agonist and an amylin agonist showing early promise in weight management and glucose regulation. As a narrative review, this paper synthesizes existing literature rather than generating new primary data, which limits its ability to establish causation or provide definitive efficacy conclusions.
Diabetes therapy : research, treatment and education of diabetes and related disorders · May 2025DOI ↗ Limited · human
This prospective qualitative study surveyed 104 consecutive patients attending a pigmented lesion clinic at a tertiary referral dermatology centre in Ireland to examine the characteristics, attitudes, and behaviours of sunbed users. Using an anonymous self-reported questionnaire, researchers collected data on demographics, frequency of sunbed use, motivations, and use of unregulated tan-enhancing agents such as Melanotan I and II. The study found that sunbed users were predominantly younger women living in urban areas, consistent with prior literature. Regulatory non-compliance was widespread: over half of sunbed premises reportedly did not provide protective goggles, and nearly half offered no health risk information to customers. Key motivations for use included improving appearance and self-confidence. Notably, greater awareness of health risks did not correlate with reduced sunbed use, suggesting a potentially compulsive or addictive behavioural pattern. Users of tan-enhancing agents also used sunbeds more frequently than non-users. The authors suggest psychological interventions such as cognitive behavioural therapy may be beneficial and call for stricter regulatory enforcement. Limitations include the single-centre design, small sample size, self-reported data susceptible to bias, and a clinic-based population that may not represent the general public.
Skin health and disease · May 2025DOI ↗ Review
This review article examines the management of type 2 diabetes and obesity, with a particular focus on CagriSema, an investigational combination drug pairing cagrilintide (an amylin analog) with semaglutide (a GLP-1 receptor agonist). The authors begin by contextualizing the scale of diabetes in the United States—affecting over 37 million people—and highlight the interplay between obesity and type 2 diabetes, noting that genetic and physiological barriers often make weight loss difficult without pharmacological support. The article reviews the pathophysiology of diabetes, current clinical guidelines, and the risks associated with intensive glycemic control, particularly hypoglycemic events such as cardiac arrhythmias, confusion, coma, and death. It then surveys the existing evidence for approved weight loss and antidiabetic medications before summarizing recent clinical trial data on CagriSema, which is being investigated as a potentially superior agent for reducing both HbA1c and body weight. The authors argue that CagriSema may offer a favorable safety and efficacy profile, though they acknowledge the drug remains under investigation. Key limitations include the review format itself—primary trial data are summarized rather than independently analyzed—and the absence of long-term safety data for CagriSema in the published literature reviewed.
Cardiology in review · May 2025DOI ↗ Review
This narrative review examines the current landscape and future directions of Type 2 Diabetes Mellitus (T2DM) treatment. The authors begin by describing conventional therapies — including metformin, sulfonylureas, and insulin — noting their limitations such as adverse effects, declining efficacy over time, and suboptimal glycemic control in many patients. The review then surveys a range of emerging therapeutic strategies. Dual incretin receptor agonists (e.g., tirzepatide), which co-activate GLP-1 and GIP receptors, are highlighted for their effects on insulin secretion, glucagon suppression, and weight loss. Dual SGLT1/2 inhibitors (e.g., sotagliflozin) are discussed for their dual gut-and-kidney glucose-lowering mechanism. Additional experimental approaches covered include glucagon receptor antagonists, GPR119 agonists, FGF21 analogs, AMPK activators, and CRISPR-Cas9 gene editing technologies. The authors acknowledge that while these novel therapies demonstrate promise in early-stage research, long-term safety and efficacy data in humans remain limited. As a narrative review, this paper does not present original clinical data, does not include a systematic search protocol or meta-analytic methodology, and is subject to selection bias in the literature discussed.
Biochemistry and biophysics reports · May 2025DOI ↗ Limited · human
This study investigated the role of CCN5, a matricellular protein, in preventing vascular restenosis after stent implantation (in-stent restenosis, ISR). Using RNA sequencing of stent-implanted porcine coronary arteries and single-cell RNA sequencing of mouse femoral artery injury models, the researchers found that CCN5 expression was reduced in vascular smooth muscle cells (VSMCs) following injury but elevated in regenerating endothelial cells (ECs). In ISR patients, plasma CCN5 levels were significantly lower and correlated inversely with restenosis severity. Using cell-type-specific loss- and gain-of-function mouse models, the study found that EC- and VSMC-specific deletion of CCN5 worsened neointimal hyperplasia, while CCN5 overexpression was protective. Mechanistically, CCN5 was found to interact with thymosin β4 (Tβ4) in ECs, promoting endothelial repair via the cleavage product Ac-SDKP, and also interacted with CD9 to support EC recovery. A CCN5 recombinant protein (CCN5rp)-coated stent deployed in a porcine model significantly increased endothelial strut coverage and reduced neointimal formation. Limitations include the translational gap between animal models and humans, and the observational nature of the patient plasma data.
European heart journal · May 2025DOI ↗ Review
This scoping review systematically examined clinical research on anti-obesity medications (AOMs) conducted in Arab countries, drawing on five databases and covering publications up to October 2024. Researchers identified 59 eligible clinical studies published between 2014 and 2024, the large majority of which (89.8%) were observational in design. Most research originated from Saudi Arabia (40.7%) and the United Arab Emirates (20.3%). Glucagon-like peptide-1 (GLP-1) receptor agonists were the most studied drug class, appearing in 72.9% of studies, with liraglutide being the single most investigated agent (54.2%). The primary efficacy outcomes reported across studies were changes in total body weight, body mass index, and proportion of weight loss. Gastrointestinal side effects were noted in 32.2% of patients across studies. Risk of bias was assessed using the Newcastle-Ottawa scale and a modified randomized controlled trial tool. The authors highlight a notable gap: newer agents such as semaglutide and tirzepatide are underrepresented in the literature. Key limitations include the predominance of observational designs, geographic concentration, and limited data on diverse Arab subpopulations, which collectively constrain causal inference and generalizability.
Saudi medical journal · May 2025DOI ↗