Short-term weight loss and body composition changes in patients with obesity by GLP-1 and GIP/GLP-1 receptor agonists in combination with low-calorie diet. - Short-term therapeutic effects of GLP-1 and GIP/GLP-1 receptor agonists on patients with obesity during severe energy restriction.

开始日期2023-11-30

申办/合作机构-

JPRN-jRCT1031230422

/ Recruiting临床2期IIT

Single-center exploratory study: Evaluation of therapeutic impact GLP-1 a gonist on glucose and lipid metabolism and fatty liver disease in obesity u sing genomic information

开始日期2023-10-24

申办/合作机构-

100 项与 Glucagon-Like-Peptide-1(Original Biomedicals) 相关的临床结果

登录后查看更多信息

100 项与 Glucagon-Like-Peptide-1(Original Biomedicals) 相关的转化医学

登录后查看更多信息

100 项与 Glucagon-Like-Peptide-1(Original Biomedicals) 相关的专利（医药）

登录后查看更多信息

1,592

项与 Glucagon-Like-Peptide-1(Original Biomedicals) 相关的文献（医药）

2026-02-01·Neural Regeneration Research

Topical administration of GLP-1 eyedrops improves retinal ganglion cell function by facilitating presynaptic GABA release in early experimental diabetes

Article

作者: Zhang, Ti-Hui ; Wang, Lu ; Weng, Shi-Jun ; Wang, Yong-Chen ; Ruan, Hang-Ze ; Shao, Yu-Qi ; Zhong, Yong-Mei ; Liu, Yun-Feng ; Yang, Xiong-Li

JOURNAL/nrgr/04.03/01300535-202602000-00048/figure1/v/2025-05-17T081902Z/r/image-tiff Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell loss contributing to visual dysfunction or blindness. In the brain, defects in γ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders, whereas glucagon-like peptide-1 has demonstrated neuroprotective effects. However, it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells. In the present study, we used the patch-clamp technique to record γ-aminobutyric acid subtype A receptor–mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats. We found that early diabetes (4 weeks of hyperglycemia) decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude, suggesting a reduction in the spontaneous release of γ-aminobutyric acid to retinal ganglion cells. Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency, subsequently enhancing the survival of retinal ganglion cells. Concurrently, the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39, a specific glucagon-like peptide-1 receptor antagonist, or SR95531, a specific antagonist of the γ-aminobutyric acid subtype A receptor. Furthermore, extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON- and OFF-type retinal ganglion cells. This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation. Moreover, multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells. Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1. These results suggest that glucagon-like peptide-1 facilitates the release of γ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor, leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy. Collectively, our findings indicate that the γ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy. Furthermore, the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.

2025-12-31·Gut Microbes

Hypoglycemic effect of C. butyricum -pMTL007-GLP-1 engineered probiotics on type 2 diabetes mellitus

Article

作者: Xu, Xuan ; Chen, Tingtao ; Wei, Jing ; Hu, Gang ; Li, Shengjie ; Qi, Zhanghua ; Zhou, Dexi ; Wang, Yufan ; Liu, Qiong

Diabetes mellitus (DM) is a complex metabolic disease characterized by hyperglycemia. Recently, the incidence of diabetes has increased exponentially, and it is estimated to become the seventh leading cause of global mortality by 2030. Glucagon-like peptide-1 (GLP-1), a hormone derived from the intestine, has been demonstrated to exert remarkable hypoglycemic effects. However, its limitation lies in its short plasma half-life, necessitating the continuous intravenous injection of GLP-1 drugs to achieve efficacy. Here, we engineered Clostridium butyricum to continuously express and deliver GLP-1 (denoted as Cb-GLP-1), and assessed its therapeutic efficacy in type 2 diabetes mellitus (T2DM) mice. We demonstrated that administration of Cb-GLP-1 effectively lowered blood glucose levels, regulated dyslipidemia, and ameliorated hepatic impairment in T2DM mice. Furthermore, Cb-GLP-1 treatment facilitated insulin secretion by retarding islet cell apoptosis and activating the glucagon-like peptide 1 receptor/adenylate cyclase/protein kinase A (GLP-1 R/AC/PKA) signaling pathway. Gut microbiota analysis revealed that Cb-GLP-1 restored gut homeostasis disrupted in T2DM mice, as indicated by the decreased abundance of Lactobacillus and Providencia genera in response to Cb-GLP-1 treatment. Collectively, the intestinal microbiota regulation and hypoglycemic effect of the engineered strain Cb-GLP-1 presents a promising approach for diabetes management.

2025-12-31·DRUG DELIVERY

Integrating micro-needle jet injection and sustained GLP-1 therapy with structured feeding: a comprehensive strategy for obesity management

Article

作者: Long, Luoxin ; Wang, Yuji ; Hu, Hong ; Zhang, Aoran ; Zhou, Xinjin ; Mao, Lindsey F. ; Yan, Yi ; Wang, Jing ; Mao, Shanhong ; Zhang, Chen

Obesity is a global health crisis strongly linked to increased risk of type 2 diabetes, cardiovascular diseases, and other metabolic disorders. Glucagon-like peptide-1 (GLP-1) has emerged as an effective macromolecular therapeutic agent for weight management. This study addressed obesity management from three distinct perspectives: enhancing drug dispersion and bioavailability through a novel drug delivery device, extending drug half-life by developing sustained-release formulations, and sustaining the weight loss through implementation of structured dietary protocols. A new technology, micro-needle jet injection (MNJI) was developed to deliver both standard semaglutide formulations and highly viscous sustained-release formulations, achieving 100% subcutaneous delivery with predictable results. Modulation of MNJI parameters enabled the generation of various dispersion profiles, resulting in higher bioavailability compared to both needle injection (NI) and needle-free jet injection (NFJI). Sustained-release formulations, effectively administered via MNJI, exhibited higher bioavailability than the non-sustained release formulation, and positively impacted weight management efficacy in two distinct ways. First, a single injection achieved the same weight loss as five daily administrations of non-sustained release formulation. Second, a subsequent injection of the sustained-release formulations resulted in a further body weight reduction to 18%, contrasting sharply with the plateau at 13% observed in the standard formulation administered daily (p < 0.05). Finally, dietary management, particularly time-restricted feeding, successfully maintained weight loss at ∼18% below baseline levels. Collectively, the combination of MNJI delivered sustained-release formulations and structured dietary protocols offers a promising and patient-friendly strategy for long-term obesity management, improving both adherence and therapeutic outcomes.

339

项与 Glucagon-Like-Peptide-1(Original Biomedicals) 相关的新闻（医药）

2025-09-20

·EndPoints

This year’s Endpoints 11 winners; Monarez testifies to Congress; Eli Lilly’s obesity pill lags; and more

Welcome back to Endpoints Weekly! This week, our team gathered in Boston to honor 11 of the most promising biotech startups of 2025. Be sure to check out this year’s list of companies chasing bold ideas and making big scientific bets. Our team also covered a group of closely-watched meetings this week: former CDC Director Susan Monarez’s testimony before the Senate HELP Committee, and a meeting of the CDC’s Advisory Committee on Immunization Practices. Read more below. Elizabeth Cairns has the latest on Eli Lilly’s obesity pill data, and Kyle LaHucik reported on another big deal for Novartis, as well as Genmab’s decision to end work on an ADC. We’ll be back in your inbox on Monday! — Nicole DeFeudis 🏆 Meet the most exciting biotech startups of 2025 with this year’s Endpoints 11. From superintelligent AI and in vivo CAR-T in solid tumors, to oncolytic viruses and biologics-in-a-pill, this year’s winners are backed by big names in science and investing. Founding editor John Carroll broke down the winners in-depth here . Our team of reporters also profiled each of the 11 companies that earned the honor. In alphabetical order, this year’s winners are: Averna Therapeutics , Candid Therapeutics , Chai Discovery , Dispatch Bio , Judo Bio , Lila Sciences , Orbis Medicines , Sironax , Stylus Medicine , Third Arc Bio and Umoja Biopharma . Each profile is linked to the company names, where you can read more about them. And if you missed the event, an on-demand recording will be available soon! Former CDC Director Susan Monarez told senators this week that she was ousted from the agency after she declined to pre-commit to approving recommendations from the CDC’s panel of vaccine advisors and refused to fire career officials responsible for vaccine policy without cause. She testified before the Senate HELP Committee, along with former CDC chief medical officer Debra Houry, who resigned shortly after Monarez left the agency. The Endpoints team live-blogged the event here . During the hearing, both Monarez and Houry brought up concerns about the composition of ACIP, an advisory committee that makes recommendations on vaccine use in the US. Monarez said HHS Secretary Robert F. Kennedy Jr. did not consult her before adding seven new members to the committee in June. Five additional members were announced this week . Monarez said she had not “prejudged” the committee’s meeting this week, but also said during her testimony that “there is real risk that recommendations could be made restricting access to vaccines for children and others in need without rigorous scientific review.” In a meeting the following day, ACIP voted not to recommend giving children under the age of 4 the combined measles, mumps, rubella and varicella vaccine. The committee voted that children in that age group should instead receive separate measles, mumps, and rubella vaccine and varicella vaccine. ACIP weighed the new MMRV guidance due to the slightly heightened risk of febrile seizures in kids 1 to 2 years old who receive the combo shot as their first dose of the regimen. A separate vote on whether to recommend delaying the hepatitis B birth dose if a pregnant woman tests negative for the virus was postponed. The committee also voted on Friday to recommend that all people 6 months and older receive consultation from a healthcare provider before getting a Covid-19 shot. 💊 Eli Lilly has outflanked Novo Nordisk in diabetes and obesity, but one area where Lilly’s drugs continue to lag is in the oral GLP-1 category. Additional Phase 3 results presented this week continue to underscore that advantage for Novo. In Lilly’s study, 55% of those given the pill, called orforglipron, had a body weight reduction of at least 10% when the dose was titrated up to 36 mg. That was a statistically significant improvement compared to the placebo group, where only 13% of participants achieved at least 10% weight reduction. But in a similar trial for Novo’s oral Wegovy, 63% of patients taking the drug saw at least the same level of weight reduction. Oral Wegovy also saw numerically greater benefits in the proportion of patients who lost at least 15% of their body weight: 50% who took oral Wegovy reached that marker, compared to 36% in the Lilly trial. Cross-trial comparisons like these are imperfect, but it may be years before oral Wegovy and orforglipron are pitted head-to-head in the same study, if ever. Researchers attributed some of the results to the gender differences between the studies. About 36% of patients in the Lilly trial were male, compared to 21% male in the Novo study. GLP-1 drugs are known to be more effective in women than men, study leader Sean Wharton said at a press conference in Vienna where the data were presented. Read more here from senior biopharma journalist Elizabeth Cairns, who has been following the GLP-1 space closely. 🤝 The deal comes with $120 million upfront, and is focused on an undisclosed discovery target and the option to license two preclinical immunology programs. It’s the second deal Novartis has made with Monte Rosa. Last October, Novartis signed a deal with the developer of molecular glue degraders that was worth $150 million upfront and $2.1 billion in milestones. The latest deal “allows us to do more with more,” Monte Rosa chief business and legal officer Phil Nickson said in an interview with Endpoints’ Kyle LaHucik. Novartis has been on a dealmaking spree the last couple months. The pharma company announced last week that it’s buying Tourmaline Bio for $1.4 billion. It also inked multibillion-dollar siRNA collaborations with Argo Biopharmaceutical and Arrowhead Pharmaceuticals, and a $772 million partnership with BioArctic, LaHucik reported. Genmab spent $1.8 billion to acquire ProfoundBio last year, but it’s already decided to cull some of the pipeline. In an announcement this week, Genmab said it would stop development of an early-stage antibody-drug conjugate from ProfoundBio. The drug, known as GEN1107 or PRO1107, was in a Phase 1/2 study for various solid tumors, including ovarian, endometrial, and urothelial cancers. GEN1107 was designed to target PTK7, which is of interest to a handful of other biopharma companies. Eli Lilly, Sichuan Kelun Pharmaceutical and Day One Biopharmaceuticals are also researching PTK7-targeted ADCs. GEN1107 was also one of three clinical-stage programs Genmab picked up in the ProfoundBio buyout.

临床结果并购临床3期疫苗

2025-09-19

·EndPoints

Regeneron posts update on its muscle-sparing approach, a new quadruple agonist emerges at #EASD25

VIENNA — Eli Lilly was undoubtedly the star of this year’s congress of the European Association for the Study of Diabetes. Despite being slightly less effective than Novo Nordisk’s rival pill, Lilly’s oral obesity therapy orforglipron could do well in the market. And its diabetes shot Mounjaro looks likely to become the first of the new-generation incretins to crack the pediatric space. But many other companies also had a presence at the meeting in Vienna, some with GLP-1 therapies and some with more adventurous mechanisms. An update from the Phase 2 trial of Regeneron’s muscle-building drug trevogrumab was presented on Wednesday. The trial is assessing the ability of the anti-GDF8/anti-myostatin antibody to preserve lean mass in patients who are also taking Novo Nordisk’s obesity shot Wegovy. The new data showed that, of the weight lost by obesity patients after 26 weeks of therapy with Wegovy plus a low or high dose of trevogrumab, around 17% and 18% was lean mass, respectively. Of the weight lost by patients given Wegovy monotherapy, about 33% was lean mass. Updated data from the trial’s triplet arm, in which patients took Regeneron’s investigational anti-activin A antibody garetosmab as well as Wegovy and high-dose trevogrumab, were also presented. Here, just 7.4% of the weight lost was lean mass. These figures are not hugely different from the interim cut released in June . However, Regeneron reiterated that there were two deaths, both in the triplet group, that had been disclosed in June. In one case, the cause is unknown, although Regeneron said the patient had “multiple cardiovascular risk factors.” The second death was due to a cardiac arrest in a patient with a history of cardiovascular disease. Regeneron said it had “not identified a causal association” between the drug regimen and the deaths. The triplet regimen saw a “substantially higher” rate of discontinuations because of tolerability issues than the other two arms. Regeneron said that further studies are warranted, though it is unclear if this refers to the doublet or triplet regimen. Regeneron is separately seeking approval of garetosmab for the rare bone disease fibrodysplasia ossificans progressiva. Mid-stage trial data on a quadruple agonist developed by the California biotech Biomed Industries was also presented on Wednesday. Bioglutide, also called NA-931, is an oral small molecule that hits the receptors for GLP-1, GIP, glucagon and insulin-like growth factor-1 (IGF-1). In the 125-patient Phase 2 study, obesity patients taking one pill a day for 13 weeks had a maximum body weight reduction of 14.8% at the 150 mg daily dose, which calculates to 13.2 percentage points greater than placebo. Gastrointestinal adverse events were mostly mild, with nausea and vomiting reported as “insignificant.” Diarrhea occurred in 8.1% of bioglutide-treated subjects, compared to 3.2% in the placebo group. According to the EASD abstract, no muscle loss was observed. The company intends to take bioglutide into a Phase 3 program. Wednesday also saw presentation of results from a small Phase 1b/2a study of a GLP-1 developed by the Indian company Sun Pharmaceutical, in patients with obesity and metabolic dysfunction-associated fatty liver disease (MAFLD). In a subset of patients with BMI of less than 40 kg/m2 and blood sugar levels of at least 6.0%, their body weight fell by an average of 6.8% after 13 weeks of treatment with utreglutide. In the placebo group, weight fell by 3.1% but this group was not required to meet the same blood sugar criterion as those who received the drug. These patient groups were small, with just eight patients getting utreglutide and six receiving placebo. Utreglutide, with the codename GL0034, is also in a Phase 2 study in MASH with data due late next year or early in 2027. Another Asia-based biotech, Beijing QL Biopharmaceutical, presented data on a GLP-1 at the conference on Wednesday — this time, a long-acting shot with potential for monthly administration. Zovaglutide, also known as ZT002, was tested in around 300 nondiabetic obesity patients. Two doses, 80 mg or 160 mg, were given every two weeks and every four weeks in different groups. After six months, those given 80 mg monthly lost 10.6% of their weight, while those on the 160 mg monthly dose lost 13.8%. The same doses given every two weeks resulted in weight loss of 12.5% and 14.4%, respectively. All zovaglutide groups demonstrated statistically significant greater weight loss versus placebo, and no plateau was reached. Gastrointestinal adverse events (AEs) were similar to those of marketed GLP-1s, QL said , though one patient quit the trial due to gastrointestinal AEs. The company said that the data support a Phase 3 trial of monthly zovaglutide in obesity patients. Novo Nordisk reported a new data point from its early-stage trial of the GLP-1 and amylin combo shot known as amycretin on Tuesday. A cohort in the drug’s Phase 1b/2a obesity trial , whose dose was escalated up to 60 mg, lost 24.3% of their body weight at eight months, whereas placebo patients lost 1.1%. This was significantly higher, at a p-value of less than 0.001. The researchers said amycretin was “considered safe and tolerated” up to 60 mg. The most common TEAEs were nausea, vomiting and diarrhea, and most were mild to moderate. Editor’s note: This story was updated to note that the deaths in Regeneron’s study had already been disclosed, and that the company is seeking approval of garetosmab in a rare bone condition.

临床结果临床2期临床3期AHA会议

2025-09-17

·ETPharma

Novo Nordisk's Alzheimer's trial a 'lottery ticket', senior executive says

Copenhagen: A senior Novo Nordisk executive on Wednesday described the drugmaker's ongoing trial of its blockbuster obesity medicine for treatment of Alzheimer's disease as a "lottery ticket" due to its uncertain prospects yet huge potential. The Danish drugmaker expects data from its pivotal Alzheimer's disease trial by the end of 2025. After blockbuster success in weight loss, Alzheimer's could emerge as the next key frontier for GLP-1 drugs like semaglutide as drugmakers explore new applications beyond obesity and diabetes. "We always presented it as a lottery ticket and it still is because it's very uncertain," Ludovic Helfgott told Reuters in an interview during the European Association for the Study of Diabetes conference in Vienna. The Danish drugmaker is testing whether semaglutide, the active ingredient in blockbuster drugs Ozempic and Wegovy, can slow cognitive decline in early-stage Alzheimer's patients. The so-called EVOKE trials represent the first large-scale studies investigating semaglutide's disease-modifying potential in the progressive brain disorder - the most common type of dementia. Despite some investor calls to diversify, Helfgott reiterated the company's focus on obesity and diabetes and related comorbidities, suggesting no shift into other disease areas. (Reporting by Stine Jacobsen, editing by Terje Solsvik)