Research Hub
The living record of
peptide science.
PubMed studies synced daily. Active clinical trials. Evidence updates when the science materially changes. Monthly synthesis for practitioners.
Layer 1
Study feed
Evaluation of the Safety, Tolerability, Pharmacokinetics, and Efficacy of Subcutaneous Firsekibart in Gout: A Phase Ib/II Clinical Trial.
Int J Rheum Dis
Yu Xue, Ning Zhang, Jiankang Hu +23 more
This Phase Ib/II study aimed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of Firsekibart in the treatment of gout flares.
Opa1-Knocked out EMSCs-Derived EV-Mito Empower Functionalized PEEK/LL37 Scaffolds to Combat Drug-Resistant Bone Infection.
ACS Appl Mater Interfaces
Xin Yang, Chen Chen, Xianliang Rao +8 more
Treating bone defects becomes particularly challenging when drug-resistant bacteria take hold. Standard antibiotics often fail to clear these infections completely, and the resulting inflammatory environment actively blocks new bone formation. To tackle this problem, we developed a sulfonated-PEEK scaffold called SPMiL that carries two distinct payloads: the human derived antimicrobial peptide LL37 and mitochondria-rich vesicles (EV-Mito). We generated these vesicles from ectomesenchymal stem cells (EMSCs) lacking Opa1, a key regulator of mitochondrial dynamics. Knocking out this gene substantially boosts vesicle production, solving the supply limitations that have hampered previous attempts to use EV-Mito therapeutically. In tests using MRSA-infected rat calvarial defects, SPMiL released LL37 continuously to eliminate the resistant bacteria while simultaneously transferring functional mitochondria into recipient cells. These transplanted organelles promoted osteogenic differentiation and suppressed osteoclast activity through metabolic reprogramming, antioxidant effects, and restoration of mitochondrial membrane potential. This work demonstrates that combining antibacterial defense with mitochondrial transfer offers a viable approach for treating infected bone defects that resist conventional treatment.
Evaluating the Cardiovascular Benefits of Innovator Semaglutide 2.4 mg (Recombinant DNA (r-DNA)) in Patients With Overweight or Obesity: A Critical Review of Current Evidence.
Cureus
Brij Teli, Sunil Sathe, Ravi Kalra +37 more
Obesity and cardiovascular (CV) disease (CVD) are tightly intertwined global epidemics, with excess adiposity now recognized as a major, modifiable driver of atherosclerotic events, heart failure, and mortality. Despite advances in cardiometabolic care, residual CV risk remains high in people with obesity, underscoring the need for therapies that both reduce body weight and directly modify CV risk. Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), has emerged as a pivotal agent across the cardiometabolic spectrum, culminating in the SELECT trial, which demonstrated a reduction in three-point major adverse CV events (3P-MACE) in people with obesity and established CVD but without diabetes. Complementary evidence from heart failure with preserved ejection fraction (HFpEF) trials and real-world studies further supports a broad CV and functional benefit profile. This narrative review synthesizes data from randomized controlled trials (RCTs) and real-world evidence (RWE) on Wegovy® (semaglutide 2.4 mg, a recombinant DNA-derived GLP-1RA) in obesity with CVD, with a focus on SELECT, mediation analyses suggesting weight-independent CV effects, and outcomes in obesity-related HFpEF. We also discuss guideline positioning, regulatory milestones-including the 2025 Central Drugs Standard Control Organization (CDSCO) approval in India-and the evolving competitive landscape. Overall, semaglutide 2.4 mg represents the first and only anti-obesity medication with proven CV benefit in people with obesity without type 2 diabetes (T2D), with important implications for clinical practice and health policy.
Beyond Weight Loss: Early Real-World Evidence of Semaglutide in Obesity.
Medicines (Basel)
Steluța Constanța Boroghină, Amalia-Ioana Arhire, Teodora Papuc +6 more
Background: Obesity is a chronic, relapsing disease that often proves resistant to lifestyle measures alone. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), are reshaping treatment, yet prospective real-world data remain limited. Objective: To prospectively assess the effects of once-weekly Semaglutide on weight, body composition, and metabolic health in obesity. Methods: An exploratory observational study of 37 patients initiating Semaglutide (mean age 31 years; 11 children and adolescents; 22 females) was conducted. All met obesity criteria (baseline BMI 34.7 kg/m2). Anthropometry, bioimpedance body composition, and fasting biochemistry were obtained at baseline and 3 months. Variables were reported as mean ± SD or median (IQR) according to normal/non-normal distribution, whether a parametric test or a Wilcoxon one was used. Parametric or non-parametric paired tests (two-sided α = 0.05) were applied. We also explored tri-ponderal mass index (TMI, kg/m3) and its correlations with metabolic markers. Results: At 3 months, body weight decreased by a median 8.0 kg (p < 0.001), BMI by 1.6 kg/m2 (p < 0.001). Body fat percentage declined: 43.4% to 42.8% (p = 0.009), with a small reduction in skeletal muscle mass (-0.6 kg; p = 0.035). Fasting glucose improved (p = 0.030) and HOMA-IR fell significantly. HbA1c changes were minimal, consistent with near-normal baseline values. Triglycerides decreased, while total cholesterol, LDL-C, HDL-C, liver enzymes, creatinine, uric acid, and 25-OH vitamin D remained stable. Baseline TMI (median 20.13 kg/m3; IQR 3.80) correlated strongly with HOMA-IR (r = 0.766, p < 0.001) and moderately-to-strongly with body fat percentage (r = 0.621, p < 0.001). Conclusions: In this real-world cohort, Semaglutide produced rapid, clinically meaningful improvements in weight, adiposity, and insulin resistance within 3 months. Findings suggest that Semaglutide may represent a promising adjunct to lifestyle therapy in obesity management.
A survey of primary care physicians' views on supporting patients who lose insurance coverage for Glucagon-Like Peptide-1-based drugs for weight management.
Obes Pillars
Lauren Oshman, Amy Runyon, Alexis Vicenzi Bal +8 more
Glucagon-like peptide-1 (GLP-1)-based drugs for weight management are commonly prescribed by primary care physicians (PCPs), many of whom have limited familiarity with alternative weight management treatments. This knowledge gap may be especially problematic when patients lose insurance coverage for - and therefore access to - GLP-1-based drugs after initial weight loss, as these patients may require alternative treatments to sustain weight loss or maintenance. To date, little is known about how prepared PCPs feel to manage this increasingly common clinical scenario.
Circulating levels of PYY are increased in individuals with bile acid diarrhoea.
J Clin Endocrinol Metab
Andreas H Lange, Martin L Kårhus, Christopher Bannon +8 more
Bile acid diarrhoea (BAD) is a chronic disease caused by a disturbance of the enterohepatic circulation resulting in an abundance of bile acids in the colon, which in turn causes diarrhoea. Since bile acids stimulate the secretion of the hormone peptide YY (PYY), we investigated PYY levels in plasma samples from earlier studies enrolling patients with BAD and healthy volunteers.
Efficacy and Safety of Once-Weekly Semaglutide Versus Basal Insulin and Other GLP-1 Receptor Agonists in Adults With Type 2 Diabetes Uncontrolled on Oral Antidiabetic Drugs: A Systematic Review and Pairwise Meta-Analysis.
Cureus
Faisal A Aljulajil, Unaib Rabbani
Type 2 diabetes mellitus (T2DM) affects over 537 million adults worldwide. When oral antidiabetic drugs (OADs) fail, escalation to injectable therapy is required, yet no systematic review has simultaneously compared once-weekly semaglutide against basal insulin and other GLP-1 receptor agonists - specifically exenatide ER, insulin glargine, dulaglutide, and liraglutide - in insulin-naïve patients uncontrolled on OADs. This review aimed to evaluate the efficacy and safety of once-weekly semaglutide versus injectable antidiabetic therapies - specifically basal insulin (insulin glargine) and three GLP-1 receptor agonists (exenatide ER, dulaglutide, and liraglutide) - in adults with T2DM inadequately controlled on OADs, through pairwise meta-analyses of randomized controlled trials (RCTs). Five databases were searched from inception to April 2026. Eligible studies were phase 2b-4 RCTs of at least 12 weeks comparing once-weekly semaglutide against injectable therapy in insulin-naïve adults with T2DM. Two reviewers performed selection, extraction, and Cochrane Risk of Bias version 2 (RoB 2) assessment; both are co-authors with prior trial familiarity, constituting a registered protocol deviation. Random-effects pairwise meta-analyses were performed, and certainty was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Four Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) RCTs were included (n = 3,680 total; 2,705 analyzable for the primary comparison). Semaglutide 1.0 mg reduced HbA1c versus all comparators (mean difference (MD) -0.64%, 95% confidence interval (CI) -0.80 to -0.47; low certainty) and body weight (MD -4.38 kg, 95% CI -5.76 to -3.01; low certainty). Against GLP-1 RAs specifically, body weight reduction was homogeneous (MD -3.72 kg, 95% CI -4.17 to -3.28; I² = 0%; moderate certainty). Systolic BP was reduced (MD -2.32 mmHg; moderate certainty). HbA1c less than 7.0% was achieved more frequently with semaglutide (relative risk (RR) 1.60; low certainty). Hypoglycemia risk was lower versus insulin glargine (RR 0.53; moderate certainty). Gastrointestinal (GI) adverse events and treatment discontinuation were higher with semaglutide versus insulin (both low certainty). Moderate-certainty evidence supports greater body weight reduction with semaglutide versus other GLP-1 RAs and lower hypoglycemia risk versus basal insulin. Low-certainty evidence suggests HbA1c benefits versus all comparators. Certainty is limited by heterogeneity, open-label design across all included trials, and exclusive industry sponsorship by the manufacturer of semaglutide. Future independent trials are needed.
Effects of glucagon-like peptide-1 receptor agonists on metabolic outcomes in antipsychotic-treated patients with schizophrenia: A systematic review and meta-analysis.
Schizophr Res
Milene Vitória Sampaio Sobral, Rodrigo Bettanim Menechini, Jordana Belgamasco Cavalcanti Marçal +6 more
Individuals with schizophrenia have markedly increased cardiometabolic morbidity, largely attributable to antipsychotic-induced weight gain, insulin resistance, and dyslipidemia, particularly with clozapine- and olanzapine-based regimens. This systematic review and meta-analysis evaluated the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in antipsychotic-treated patients with schizophrenia.
Volumetric photoacoustic imaging of elastin and age-related remodeling using near-infrared probe ElaNIR.
Photoacoustics
Hyunseo Jeon, Jiwoong Kim, Haw-Young Kwon +5 more
Elastin supports tissue elasticity and structural stability, but its regeneration is minimal in adulthood. Monitoring elastin remodeling is therefore important for understanding aging and related cardiovascular disease. However, fluorescence imaging lacks penetration for deep-tissue visualization, while histological methods are invasive, endpoint-based, and limited in volumetric assessment. Here, we demonstrate 3D multispectral photoacoustic computed tomography (PACT) for volumetric assessment of ElaNIR, a near-infrared elastin-targeted probe. Multispectral unmixing separates ElaNIR signals from endogenous hemoglobin, enabling depth-resolved visualization of probe distribution within anatomical context. Young mice showed strong, uniform ElaNIR signals in elastin-rich tissues, including skin and ear, whereas aged mice showed reduced and discontinuous signals. In contrast, aged mice exhibit increased ElaNIR signals in clearance-related organs, including kidneys, liver, and bladder, suggesting altered probe retention and biodistribution with aging. These results establish 3D multispectral PACT as a volumetric imaging framework that integrates elastin-associated probe retention with organ-level biodistribution for interpreting age-related changes.
Hypoglycemic and Hypolipidemic Potentials of Mulberry Fermented With Lactobacillus brevis YM 1301 and Lactobacillus plantarum CICC 24202.
J Food Sci
Juan Wan, Jingru Gao, Chunying Huang +6 more
Mulberry ripe fruit (MP) is a popular berry known for its rich content of health-beneficial components such as anthocyanins and polysaccharides. While traditional Chinese medicine suggests therapeutic effects of mulberry fruits on diabetes, their high content of small-molecule sugars discourages diabetic patients from consuming them. This study utilized Lactobacillus plantarum CICC 24202 and Lactobacillus brevis YM 1301 to ferment mulberry homogenate at 37°C for 60 h. The fermented mulberry homogenate was freeze-dried to obtain fermented mulberry product (FMP). The content of small-molecular sugars in FMP decreased by approximately 50%, while the content of polysaccharides, the active components linked to the hypoglycemic effect of MP, increased by roughly 80%. The impact of FMP on type 2 diabetes (T2DM) was evaluated in a mouse model induced by a high-fat diet combined with STZ. The findings revealed that FMP and MP improved various parameters, including fasting blood glucose, serum insulin, serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol, and FMP exerted a superior improving effect on these indices than MP. In addition, FMP also elevated levels of glucagon-like peptide-1 (GLP-1) and adiponectin in serum, reduced epididymal fat accumulation, and alleviated renal function damage in diabetic mice. Therefore, lactic acid bacteria fermentation represents a promising strategy to reduce small-molecular sugars in mulberry, enrich product diversity, and improve the health-promoting properties of mulberry products.
Protracted osilodrostat-induced pan-adrenal steroidogenic suppression and adrenal size reduction in Cushing disease.
JCEM Case Rep
Yael Sofer, Rivka Kessner, Sher Matsri +2 more
Osilodrostat, a potent 11β-hydroxylase inhibitor, is used for Cushing syndrome. Transient adrenal insufficiency during dose titration is common and usually reversible, whereas prolonged adrenal insufficiency after treatment discontinuation appears uncommon. A man with treatment-resistant Cushing disease was treated with osilodrostat after prior transsphenoidal surgeries and stereotactic radiosurgery. He initially demonstrated the expected biochemical profile of 11β-hydroxylase inhibition, with elevated adrenocorticotropic hormone (ACTH) and 11-deoxycortisol concentrations. After 18 months of therapy, he developed adrenal insufficiency with morning cortisol 1.27 μg/dL (SI: 35 nmol/L) [reference 5-22.6 μg/dL; 145-619 nmol/L], ACTH 989 pg/mL (SI: 217.6 pmol/L) [reference 4-46 pg/mL; 1.0-10.1 pmol/L], suppressed aldosterone 1.2 ng/dL (SI: 33.2 pmol/L) [reference 2-35 ng/dL; 55.4-970 pmol/L], markedly elevated direct renin 288.5 mIU/mL [reference 4.4-46.1 mIU/mL], and suppression of adrenal androgen production. Osilodrostat was discontinued and glucocorticoid replacement initiated, with later introduction of mineralocorticoid replacement. At 2.5 years, glucocorticoid and androgen suppression persist, together with prolonged mineralocorticoid dysfunction and adrenal size reduction. Review of 10 previous reports suggests prolonged adrenal insufficiency is uncommon and mineralocorticoid deficiency rarely documented, while persistent androgen suppression has not previously been reported. This case highlights prolonged pan-adrenal steroidogenic suppression with adrenal shrinkage and suggests recovery of adrenal function may take years.
Ex Vivo drug sensitivity in patient-derived 3D cultures in acromegaly and its association with clinical predictors.
Pituitary
Yasutaka Tsujimoto, Atsushi Ishida, Frederico Gaia Costa da Silva +16 more
Personalized therapy in acromegaly is limited by interindividual variability in drug responses and the lack of robust markers predicting tumor shrinkage, rather than biochemical control alone. To test whether ex vivo drug-induced viability changes in patient-derived 3D cultures (Pd3D) of GH-secreting pituitary adenomas reflect tumor cell-intrinsic pharmacological sensitivity and align with established clinical predictors.
Bitter hop nutraceutical stimulates fat mass loss while preserving muscle mass in a cohort of individuals with overweight or obesity receiving diet and exercise advice.
Obes Pillars
Edward Walker, Kim Lo, Isabel Smirk +4 more
Diet and exercise advice are routinely the primary interventions given for weight loss; however, frequently result in poor weight loss outcomes. While modern pharmaceuticals are highly effective, there exists a need for a non-pharmaceutical adjunct therapy for lifestyle change-mediated weight loss. Recently, the gastrointestinal delivery of a bitter hop-based nutraceutical has been shown to stimulate increases in glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK). Our aim was to determine if this same bitter hop nutraceutical is an effective adjunct therapy during prescribed weight loss programs.
Semaglutide for prevention of type 2 diabetes in women with postpartum prediabetes after gestational diabetes: protocol for a Belgian multicentre double-blind randomised placebo-controlled trial.
BMJ Open
Yana Vanlaer, Nina Embo, Niels Bochanen +14 more
Women with postpartum pre-diabetes following gestational diabetes mellitus (GDM) are at particularly high risk of developing type 2 diabetes mellitus (T2DM). While the implementation of effective lifestyle interventions in the early postpartum period is often difficult and has in general limited efficacy to prevent T2DM after GDM, effective preventive strategies, including medical therapies, are needed in this population. The 'semaglutide for the treatment of pre-diabetes in women with prior gestational diabetes (SERENA) study' aims to evaluate the efficacy, safety and cost-effectiveness of semaglutide in preventing progression to T2DM during the early postpartum period.
Impact of semaglutide on cognitive function in patients with type 2 diabetes and mild cognitive impairment: a 24-month observational study.
Intern Emerg Med
Giuliano Cassataro, Silvia Scriffignano, Giulio Geraci +7 more
Type 2 diabetes mellitus (T2DM) is associated with an increased risk of mild cognitive impairment (MCI) and dementia. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide cardiovascular and metabolic benefits, and emerging data suggest neurocognitive effects. We conducted a 24-month prospective observational study of 72 adults (≥ 50 years) with T2DM and MCI treated with semaglutide (subcutaneous [SC] or oral) and assessed at baseline (T0) and every 6 months (T1-T4). Outcomes included anthropometrics, fasting glucose, HbA1c, LDL-c, and neuropsychological tests (Montreal Cognitive Assessment [MoCA], Digit Symbol Substitution Test [DSST], Beck Depression Inventory [BDI]). A control cohort of 60 patients with T2DM and MCI not receiving semaglutide was evaluated with the same protocol. Semaglutide was associated with significant reductions in body weight, BMI, waist circumference, fasting glucose, and HbA1c (all p < 0.05). Cognitive performance improved, as shown by MoCA scores (median Δ≈ + 4 points, p < 0.001) at T4 compared with T0; at T4, semaglutide recipients also had higher MoCA scores than controls (+ 4.0 vs - 1.5, p < 0.001). DSST and BDI scores also improved (p = 0.001 and p = 0.044, respectively). MoCA improved similarly with both formulations, whereas DSST improvement reached significance only with SC semaglutide. In multivariable regression, semaglutide independently predicted MoCA improvement (+ 4.76 points, p < 0.001). No semaglutide-treated patient progressed to dementia versus 14 in controls (p = 0.002). In adults with T2DM and MCI, semaglutide was associated with improved cognition and a lower risk of progression to dementia. Differences between formulations may reflect distinct central nervous system engagement. Randomized trials are warranted.
One receptor, two opposite approaches: efficacy and tolerability of GIPR agonism and antagonism in obesity pharmacotherapy.
Appetite
Serena X Gao, Tito Borner
Glucagon-like peptide-1 receptor (GLP-1R) agonists have transformed obesity pharmacotherapy, producing clinically meaningful weight loss and robust improvements in glycemic control. Yet their efficacy remains constrained by dose-limiting gastrointestinal adverse effects, including nausea and vomiting, that reduce adherence and limit escalation to maximally effective doses. Thus, the next-generation of obesity therapeutics must not only enhance weight loss but also expand the therapeutic window by dissociating metabolic efficacy from aversive side effects. The recent clinical success of dual GLP-1R/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists has catalyzed renewed interest in GIP biology. However, this resurgence has exposed a fundamental paradox: both pharmacological activation and blockade of GIP receptor (GIPR) signaling reduce body weight and enhance the efficacy of GLP-1-based therapies. These seemingly opposing pharmacological strategies therefore converge on a shared therapeutic outcome through distinct biological mechanisms. GIPR agonism appears to promote weight loss in part through recruitment of anorectic neural circuits, increased thermogenesis, and attenuation of GLP-1-induced aversive effects, whereas GIPR antagonism may enhance GLP-1R signaling and counteract the lipogenic actions of endogenous GIP. In this review, we examine the mechanistic basis underlying the GIPR agonism-antagonism paradox and discuss how GIPR signaling may regulate the balance between metabolic efficacy and treatment tolerability. Understanding these mechanisms may guide the rational design of next-generation incretin-based therapies that maximize weight loss while minimizing adverse effects.
Symptom severity and exacerbation frequency in medically treated patients with acromegaly.
Pituitary
Eliza B Geer, David R Clemmons, Jill Sisco +6 more
To quantify the severity, frequency of symptom exacerbations, and associated life impact of acromegaly symptoms in patients treated with injected depot somatostatin receptor ligands (SRLs).
Extending IGF-1 Receptor Inhibition Beyond Thyroid Eye Disease: A Scoping Review of Teprotumumab Administration in Pretibial Myxedema.
AACE Endocrinol Diabetes
Maxim John Levy Barnett, Maria Helena Siqueira Tavares de Melo, Maria Luiza de Medeiros Rego
Pretibial myxedema is an infrequent dermatologic manifestation of autoimmune thyroid disease characterized by glycosaminoglycan deposition within the dermis. Treatment options are limited, lacking durable effect and remain largely palliative. Emerging evidence, however, suggests pretibial myxedema may share a common pathophysiology with thyroid eye disease, raising the possibility that inhibition of the insulin-like growth factor-1 receptor may offer therapeutic benefit.
Cardiovascular and Cerebrovascular Outcomes Risk Reduction Associated With Semaglutide vs Tirzepatide: A Target Trial Emulation.
JACC Adv
Ahmed Y Azzam, Muhammed Amir Essibayi, Pranjal Rai +11 more
Glucagon-like peptide-1 receptor agonists demonstrate cardiovascular benefits; however, head-to-head comparisons between semaglutide and tirzepatide remain limited.
Advances in proteomics research related to semaglutide: evidence from humans and animals.
J Endocrinol Invest
Qiannan Jia, Hua Mu, Yuqing Wang +2 more
With the advancement of proteomics technologies, an increasing number of studies have begun to examine semaglutide-associated protein expression changes and pathway alterations across different biological contexts. However, existing evidence remains fragmented across different disease backgrounds, sample types, and research platforms, lacking systematic integration.