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Comparative Efficacy and Safety of Tirzepatide in Asian and Non-Asian Adults With Obesity Without Diabetes: A Systematic Review and Meta-Analysis.
Endocrinol Diabetes Metab
A B M Kamrul-Hasan, Ibrahim Khalil, Deep Dutta +3 more
Tirzepatide, a dual GIP/GLP-1 receptor agonist, produces substantial weight loss in adults with obesity. Given ethnic differences in obesity phenotype and cardiometabolic risk, this systematic review and meta-analysis compared tirzepatide's efficacy and safety between Asian and non-Asian adults without diabetes.
Effects of tirzepatide therapy on body weight and body composition in adults with overweight and obesity.
Front Endocrinol (Lausanne)
Haley Corso, Austin J Graybeal, Emily Hoelscher +4 more
Obesity is a growing public health concern associated with increased risk of chronic diseases, including type 2 diabetes and cardiovascular disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become a key therapeutic option for obesity management, yet real-world evidence describing short-term changes in body composition, particularly with newer agents such as tirzepatide, remains limited. This retrospective study examined changes in body weight, body mass index (BMI), and body composition among adults with obesity receiving GLP-1 receptor agonist therapy within a clinical obesity medicine program that included individualized lifestyle guidance. Thirty-five adults (53.4 ± 7.8 years; BMI 37.2 ± 9.16 kg/m²) receiving tirzepatide were evaluated. Therapy was initiated at 2.5 mg or 5 mg once weekly, with scaffolded dose escalation up to 15 mg based on tolerance and clinical response. Body weight was measured using standard procedures, and body composition was assessed with bioelectrical impedance analysis (InBody770) at baseline and follow-up visits. Linear mixed models and ANOVA were used to examine effects of time, sex, and baseline weight status (p < 0.050).GLP-1RA therapy resulted in significant reductions in body weight (-31.1 kg; -27.8%), BMI (-10.4 kg/m²; -27.8%), body fat percentage (-16.2%; -37.6%), fat mass (-26.4 kg; -54.2%), fat-free mass (-4.5 kg; -7.3%), skeletal muscle mass (-2.8 kg; -8.3%), and total body water (-3.5 kg; -7.7%) (all p < 0.001). Weight loss was predominantly attributable to fat mass, comprising 85.7% (95% CI: 81.9, 89.5) of total weight loss, with smaller contributions from fat-free and skeletal muscle mass. Reductions in extracellular (-2.6 kg; -9.5%) and intracellular water (-1.3 kg; -7.4%) were observed; however, fluid distribution indices did not change significantly over time.Sex-specific analyses showed females experienced greater percentage reductions in fat mass, fat-free mass, skeletal muscle mass, and total body water compared to males, while males exhibited greater reductions in fluid ratios (p < 0.05). Participants with higher baseline BMI demonstrated significantly greater percentage reductions in weight, BMI, fat mass, and body fat percentage compared to those with lower baseline BMI (p < 0.05), although post-treatment values were not significantly different between groups.
Real-world treatment satisfaction and experience with once-weekly tirzepatide: Insights from prescribing physicians and people with obesity or overweight.
Obes Pillars
Theresa Hunter Gibble, Andrea Leith, Lewis Harrison +4 more
Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated its efficacy in clinical trials; however, real-world evidence on treatment satisfaction and experiences among people with obesity or overweight (PwO) and their prescribing physicians remains limited. This study aimed to assess the real-world clinical characteristics, treatment patterns, and satisfaction with tirzepatide among PwO without type 2 diabetes (T2D) and their prescribing physicians in the United States.
Weight Loss Following Liraglutide Therapy in a Patient With Smith-Magenis Syndrome: A Case Report.
Cureus
Dave K Garg, Jeffrey Wei
This case reviews the use of a Glucagon-Like Peptide-1 Receptor Agonist (GLP1RA) in a young man presenting with excessive hunger and rapid weight gain compounded by an underlying rare form of genetic obesity, Smith-Magenis syndrome. The patient had, prior to presentation, seen an accelerated and persistent weight gain over the last five years despite attempts at portion control and behavior modification. Due to concerns of worsening metabolic disease, including prediabetes, dyslipidemia, and fatty liver disease, we started the patient on daily liraglutide and gradually titrated to the maximum dose over five months. He was able to tolerate the medication without severe gastrointestinal side effects, and alongside lifestyle and behavioral modifications, the patient lost 22.2 kg (49 lbs) over the course of 11 months. To our knowledge, there is only one other published case report documenting the use of GLP1RA therapy in a patient with Smith-Magenis syndrome.
Contractile effects of albiglutide in the human and mouse atrium.
Front Endocrinol (Lausanne)
Joachim Neumann, Milena Jarikova, Uwe Kirchhefer +2 more
Albiglutide was developed as a glucagon-like-peptide 1 receptor (GLP-1R) agonist for the treatment of type 2 diabetes. We tested the hypothesis that albiglutide exerts a positive inotropic effect in the human heart via GLP-1R by measuring contractility in paced (1 Hz) human atrial preparations (HAP) from adult patients who underwent surgery for severe coronary heart disease. We observed a time- and concentration-dependent positive inotropic effect of albiglutide in HAP; this effect began at 10 nM albiglutide and increased to 100 nM albiglutide, the highest concentration studied. The positive inotropic effect of albiglutide was accentuated by the phosphodiesterase III inhibitor cilostamide (100 nM) and reduced by 10 µM N-[2-[[(E)-3-(4-bromophenyl)prop-2-enyl]amino]ethyl]isoquinoline-5-sulfonamide, an inhibitor of the 3',5' cyclic adenosine monophosphate-dependent protein kinase. Conversely, the effect was not reversed by 10 µM propranolol, a β-adrenoceptor antagonist, and was less effective than the effect of 1 µM isoprenaline. In the presence of cilostamide, the endogenous agonist GLP-1(7-36)amide at 100 nM augmented the force of contraction in HAP, whereas its precursor, GLP-1(1-36)amide, did not. Contractile force in abligutide-treated (100 nM) HAP in the presence of cilostamide was further enhanced by 100 nM GLP-1(7-36)amide or 10 nM exenatide but was not affected by 100 nM GLP-1(1-36)amide. After the addition of cilostamide, 100 nM albiglutide augmented the rate of tension relaxation and accelerated the time to relaxation in HAP. In contracting HAP, 100 nM albiglutide in the presence of 100 nM cilostamide increased the phosphorylation state of phospholamban and the inhibitory subunit of troponin. In HAP, the positive inotropic effects of albiglutide-both alone and in the presence of 100 nM cilostamide-were attenuated by treatment with 100 nM exendin(9-39), a GLP-1R antagonist. In contrast, 100 nM albiglutide did not increase the force of contraction or the beating rate in isolated left atrial or right atrial preparations from adult mice in the presence and absence of the phosphodiesterase 4 inhibitor rolipram (100 nM). Our data suggest that albiglutide increases the force of contraction via stimulation of GLP-1R and cAMP-dependent phosphorylation in HAP. Albiglutide acts as a partial GLP-1R agonist in HAP. This indicates that any clinical side effects of albiglutide may be less pronounced than those of full GLP-1R agonists.
GLP-1 receptor agonists in Parkinson's disease: a meta-analysis revealing motor benefit and highlighting mood improvement.
Front Neurol
Yutong Chen, Zhehao Zhang, Zheng Liu +4 more
GLP-1 receptor agonists (GLP-1RAs) show promise for Parkinson's disease (PD), but their comprehensive efficacy and safety profiles remain unclear.
Cellular senescence and inflammageing: from mechanisms to senotherapeutic interventions.
Biogerontology
Piotr Paweł Chmielewski
Cellular senescence is a context-dependent cellular state characterised by persistent cell-cycle arrest, epigenetic remodelling, metabolic reprogramming and acquisition of a senescence-associated secretory phenotype. Transient senescence contributes to embryogenesis, tissue repair and tumour suppression, whereas persistent senescent cell populations accumulate with advancing age across multiple tissues, in part owing to declining immune-mediated clearance and intrinsic resistance to apoptosis, thereby promoting chronic systemic inflammation, tissue fibrosis, stem-cell dysfunction and propagation of secondary senescence. Experimental genetic and pharmacological evidence supports a contributory and in several contexts causal role for senescent cells in cardiovascular, metabolic, musculoskeletal, fibrotic and neurodegenerative disorders. These findings have accelerated the development of senotherapeutic strategies, including senolytics, senomorphics and immune-mediated clearance approaches, with early clinical studies showing preliminary evidence of functional benefit in idiopathic pulmonary fibrosis and diabetic kidney disease. However, clinical translation remains constrained by senescence heterogeneity, limited biomarker specificity and unresolved long-term safety concerns. Improved molecular, spatial and functional resolution of senescent states will be essential for developing biomarker-guided and tissue-specific interventions that preserve the beneficial functions of transient senescence while limiting its chronic deleterious effects.
Long-chain fatty acid utilization in Eisenmenger syndrome.
Prog Pediatr Cardiol
Omer Cavus, Manisha J Oza, Austin Angelotti +4 more
Morbidity and mortality in idiopathic pulmonary arterial hypertension (iPAH) are linked to right ventricular failure (RVF), a condition characterized by a metabolic shift from fatty acid oxidation (FAO) to glycolysis. Eisenmenger Syndrome (ES), a unique form of PAH, is associated with a mortality paradox, yet the mechanism for better survival in this condition remains poorly understood.
Case Report: Whole-body electrical muscle stimulation as an adjunctive tool in cardiac rehabilitation of a patient with heart failure and reduced ejection fraction.
Front Cardiovasc Med
Damian Sendrowski, Agata Polańska-Szczap, Beata Hus +4 more
Whole-body electrical muscle stimulation (WB-EMS) is an emerging modality that simultaneously activates multiple large muscle groups via a wearable electrode suit. Although localized neuromuscular electrical stimulation (NMES) has demonstrated efficacy as an adjunctive strategy in cardiac rehabilitation (CR), WB-EMS has not previously been investigated in patients with heart failure and reduced ejection fraction (HFrEF) undergoing CR.
Dapagliflozin Augmentation of Sacubitril/Valsartan Therapy in Patients With Heart Failure Following PCI-Treated Acute Myocardial Infarction: A Meta-Analysis of Clinical Efficacy and Safety.
Cardiol Res Pract
Tang Tang, Huimin Yu, Yun Zhang +2 more
To systematically review the efficacy and safety of dapagliflozin and sacubitril/valsartan (SV) in patients with heart failure (HF) following percutaneous coronary intervention (PCI)-treated acute myocardial infarction (AMI) and to provide evidence for clinical practice.
Comprehensive Bioactivity-Guided Isolation, DeepSAT, and LC-Q-TOF-MS/MS Analysis to Reveal Hypoglycemic Constituents of Momordica charantia L.
J Food Sci
Hua-Wei Lv, Wen-Lin Fan, Ruo-Han Shi +4 more
Activation of intestinal bitter taste receptors can stimulate the release of glucagon-like peptide-1 (GLP-1), thereby enhancing insulin secretion and exerting a hypoglycemic effect. In this study, a combination of bioactivity-guided screening and chemical analysis was applied to search for potential components from Momordica charantia L. that exert hypoglycemic effects via bitter taste receptors. Combined with molecular networking and DeepSAT analysis, the active fraction was found to be rich in cucurbitane-type triterpenoids, from which five pure compounds were isolated and identified. In conjunction with LC-Q-TOF-MS/MS analysis, an additional 24 cucurbitane-type triterpenoids were also identified from the active fraction. Bioactivity evaluation revealed that five compounds exhibited stimulatory effects on GLP-1 secretion in Caco-2 cells; Compounds 2 and 4 increased GLP-1 secretion to 1.40-fold and 1.35-fold of the basal level at 5 µM, respectively. These results indicate that cucurbitane-type triterpenoids may responsible for the potential hypoglycemic effect of M. charantia L. via bitter taste receptors. PRACTICAL APPLICATIONS: Cucurbitane-type triterpenoids derived from M. charantia L. are capable of stimulating the secretion of GLP-1 in intestinal cells, indicating their potential hypoglycemic activity. These compounds are promising as natural bioactive substances for the development of functional foods aimed at blood glucose homeostasis regulation. Furthermore, this provides a valuable research direction for the screening of natural hypoglycemic agents based on bitter taste receptors.
Hypersensitivity Reaction to Tirzepatide With Demonstrated Tolerance to Semaglutide: A Case Report.
Clin Case Rep
Cameron Nejat, Robert Lin, Daniel Addo +2 more
Hypersensitivity reactions to glucagon-like peptide-1 receptor agonists (GLP-1RAs) are uncommon but clinically significant given their expanding use for obesity and type 2 diabetes. Tirzepatide, a dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, and reports of allergic reactions remain limited. We present this case to highlight the diagnostic utility of intradermal testing and supervised drug challenge in confirming drug-specific hypersensitivity and identifying a safe therapeutic alternative within the same drug class. We report a 25-year-old woman with class I obesity (BMI 32.25) who developed hypersensitivity reactions after dose escalation of tirzepatide initiated for weight management. She tolerated 3 months of sequential dose escalations from 2.5 mg through 7.5 mg without adverse reaction, losing approximately 20 lbs. during this period. Following her first 10 mg dose, she developed episodic lip angioedema and generalized urticaria over the subsequent 4 days, without respiratory or gastrointestinal symptoms. Symptoms persisted despite intramuscular diphenhydramine, a 5-day course of prednisone, and two emergency department visits with intravenous steroids, ultimately resolving only after tirzepatide discontinuation. Laboratory evaluation conducted approximately 8 months prior to the reaction, following a separate self-limited episode of lip swelling unrelated to tirzepatide, had demonstrated normal total IgE, normal C1 esterase inhibitor protein and function, and normal complement levels, effectively excluding hereditary and acquired angioedema. H. pylori urea breath testing obtained, and allergy evaluation (which excluded food and seasonal allergies) was negative. Percutaneous skin testing to tirzepatide was negative; however, intradermal testing at 1:10 dilution was positive (8 mm wheal, 8 mm flare), confirming drug hypersensitivity. Intradermal testing to semaglutide was negative. A supervised subcutaneous challenge with semaglutide 0.25 mg was well tolerated, and the patient was cleared to initiate semaglutide under endocrinology oversight. The patient has since continued semaglutide without recurrence. This case illustrates tirzepatide-specific hypersensitivity and highlights the diagnostic value of intradermal testing and supervised challenge in guiding safe continuation of therapy with alternative GLP-1RAs.
Personalization of incretin therapy: can GLP-1 and GIP receptor polymorphisms influence therapy response?
J Endocr Soc
Sandro La Vignera, Rosita A Condorelli
Incretin-based therapies-glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide and the dual GLP-1/GIP receptor agonist tirzepatide-have transformed the management of type 2 diabetes (T2D) and obesity. However, substantial interindividual variability in therapeutic response remains incompletely explained by clinical factors alone.
Case Report: Pediatric ACTH-secreting pituitary adenoma presenting with hypertension and anuria.
Front Endocrinol (Lausanne)
Jiaxin Li, Wei Xia, Mengxing Wu
Adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are rare endocrine neoplasms. Pituitary apoplexy, caused by acute hemorrhage or infarction within the tumor, is an uncommon complication. Pediatric cases of ACTH-secreting adenomas with apoplexy are exceptionally rare, with limited understanding of their clinical and imaging manifestations. This report aims to enhance diagnostic awareness through a detailed case analysis.
Fourteen-year bridge to cure in occult ectopic ACTH syndrome: resection of a 3-mm pulmonary carcinoid.
JCEM Case Rep
Nobuyuki Koriyama, Takahiko Obo, Kazuma Ogiso +3 more
Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) often involves occult microtumors, making localization challenging. We report a 68-year-old woman with severe ACTH-dependent hypercortisolism in whom the primary tumor remained occult despite extensive imaging, including 68Ga-tetraazacyclododecanetetraacetic acid-D-Phe(1)-Tyr(3)-octreotide positron emission tomography/computed tomography. Based on a positive octreotide challenge test, she received long-acting release octreotide for over a decade, achieving sustained biochemical stability. In 2020, she developed breast cancer, with the tumor being ACTH-negative on immunohistochemistry. In 2023, during resection of pulmonary metastases of the breast cancer, a 3-mm nodule was incidentally discovered in the adjacent lung tissue. Through close interdisciplinary coordination, the nodule was removed and was confirmed as an ACTH- and somatostatin receptor (SSTR) 2-positive pulmonary carcinoid. Thereafter, the EAS resolved completely with prompt recovery of adrenal function. In this case, intensive medical stabilization in occult EAS probably served as a strategic "bridge to surgery." Importantly, long-term biochemical control using somatostatin analogs facilitated prompt recovery of the hypothalamic-pituitary-adrenal axis immediately after tumor resection. This may also have preserved SSTR2 expression, potentially by mitigating cortisol-induced receptor downregulation, facilitating its eventual localization. This report shows that meticulous multidisciplinary communication during unrelated surgical procedures is indispensable for identifying radiologically occult lesions.
Cushing Syndrome During Pregnancy Presenting With Neuropsychiatric Symptoms.
AACE Endocrinol Diabetes
Nattawut Permsiriphan, Wasita Warachit Parksook, Nitchakarn Laichuthai +1 more
Cushing syndrome (CS) in pregnancy is a rare condition characterized by endogenous hypercortisolism. This case is particularly noteworthy because the patient presented with psychogenic nonepileptic seizures (PNES), a neuropsychiatric manifestation that is seldom documented as a primary presentation of adrenocorticotropic hormone (ACTH)-independent CS during gestation. The objective of this report is to describe a patient with a cortisol-producing adrenal adenoma during pregnancy with the aim of highlighting the diagnostic challenges of managing rare neuropsychiatric symptoms and refractory hypertension.
Successful Use of Continuous Etomidate Intravenous Infusion for Treatment of Ectopic Cushing Syndrome due to Small Cell Lung Carcinoma With Perforated Sigmoid Diverticulitis.
AACE Endocrinol Diabetes
Aizaaz Ahmad Faiz, Muhammad Bilal Shahid, Joseph Norman +2 more
We present a case of ectopic Cushing syndrome (CS) due to small cell lung cancer with a rare complication of perforated sigmoid colon diverticulitis managed by continuous etomidate intravenous infusion (CEII) with adequate control of hypercortisolism in the perioperative period during nothing by mouth state.
Persistent Adrenocortical Insufficiency After Long-Term Metyrapone Treatment for Cushing's Disease.
AACE Endocrinol Diabetes
Satoshi Yamagata, Tomohiro Kawaguchi, Hannah M Nakamura +3 more
Cushing's disease is caused by pituitary tumors that secrete excess adrenocorticotropic hormone (ACTH). Metyrapone is widely used for medical management as a bridge to transsphenoidal pituitary surgery.
Triphasic Adrenocorticotropic Hormone Dynamics During Immune Checkpoint Inhibitor Therapy in a Patient With Malignant Melanoma.
AACE Endocrinol Diabetes
Natsumi Kuwata, Natsuko Ohashi, Maya Yonishi-Nakamura +8 more
Immune checkpoint inhibitor (ICI)-related hypophysitis is generally considered to cause irreversible adrenocorticotropic hormone (ACTH) deficiency, requiring long-term glucocorticoid replacement. However, recent reports have described transient ACTH elevation before the onset of adrenal insufficiency. We report a patient with malignant melanoma who developed a previously unreported triphasic pattern of ACTH dynamics during ICI therapy.
Vasopressin stimulation testing in hospitalized foals.
J Vet Intern Med
Myriah Albrecht, Javier Perez, David Wong +4 more
Hypothalamic-pituitary-adrenal gland axis (HPAA) dysfunction impairs survival and can be diagnosed with an arginine vasopressin (AVP) stimulation test.