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Medscape
24-07-2025
- Health
- Medscape
What Factors Influence a Patient's Success on GLP-1s?
Longer treatment duration, not having diabetes, and using semaglutide were among the factors associated with better weight reduction over 12 months among patients taking GLP-1 receptor agonists (RA), a cohort study suggested. 'Treatment responses differ among patients receiving GLP-1 RAs, and the weight fluctuations and associated factors following [their] use have not been adequately characterized,' Linong Ji, MD, of Peking University People's Hospital in Beijing, China, told Medscape Medical News . The findings, published online in Diabetes, Obesity and Metabolism , 'may provide novel insights into weight fluctuations after GLP-1 RA treatment in a real-world setting,' he said, potentially advancing the development of individualized strategies for patients. 'Corroborates Other Studies' Researchers conducted a real-world, single-center, retrospective study of 679 patients with overweight or obesity who initiated GLP-1 RA treatment between November 2022 and October 2024. At baseline, participants had a mean age of 37 years, and 31% were men. The mean BMI was 33.4, and 21% were diagnosed with diabetes. The GLP-1 RAs used in the study included semaglutide (Ozempic), liraglutide (Victoza), lixisenatide (Lyxumia), beinaglutide (Yishengtai), exenatide (Bydureon), dulaglutide (Trulicity), and PEG-loxenatide (Fulaimei). All were available for participants with both type 2 diabetes (T2D) and overweight/obesity. For participants with overweight/obesity but without T2D, only Ozempic or Victoza were routinely prescribed, with off-label documentation and informed consent. Weight measurements were collected during in-person clinic visits, and weight fluctuation curves were stratified into three phenotypes — Successful Weight Reduction, Remaining Stable, and Weight Regain. Subsequently, the association between potential influencing factors and weight fluctuations was estimated by univariate and multivariate logistic regression. Subgroup analyses were performed in participants with obesity, prediabetes, and in those using liraglutide or semaglutide. Researchers found significant differences in the duration of GLP-1 RA treatment across groups at the 3-, 6-, and 12-month follow-ups. The Successful Weight Reduction group had a significantly longer duration of GLP-1 RA treatment than the Remaining Stable group and a longer duration at both the 6- and 12-month follow-ups than the Weight Regain group. Diabetes status also showed group differences. At both the 3- and 6-month follow-ups, the proportion of patients with T2D in the Successful Weight Reduction group was lower than in the Remaining Stable group. Types of GLP-1 RAs varied between groups, and at the 3- and 6-month follow-ups, the Successful Weight Reduction group was more likely to have initiated treatment with semaglutide than the Remaining Stable group. Patients with a longer duration of GLP-1 RA treatment (odds ratio [OR], 1.014) and higher Homeostasis Model Assessment of Beta-Cell Function levels (OR, 4.912) were more likely to achieve successful weight reduction at the 12-month follow-up. Nondiabetic status (OR, 2.176) and using semaglutide (OR, 2.138) were associated with successful weight reduction at the 6-month follow-up. In addition, a higher percentage of body fat in both men (OR, 3.990) and women (OR, 2.266) was associated with successful weight reduction. The weight regain group had a higher baseline estimated glomerular filtration rate than the Successful Weight Reduction group and the Remaining Stable group at 3-month follow-up, especially among participants with prediabetes. Ji said this finding surprised him. Patients with obesity often exhibit a state of renal hyperfiltration, characterized by elevated renal plasma flow and glomerular filtration rate, which can be reversed by weight reduction. The finding suggests that patients with renal hyperfiltration might be less likely to experience durable weight reduction, Ji said. 'However, few studies have revealed similar observations. Therefore, further validations and investigations are still needed for this finding.' Furthermore, the team found a positive nonlinear association of serum creatinine with successful weight reduction at 12 months — a finding that will also require additional investigations to examine the mechanism underlying the association. Overall, Ji concluded that while longer duration of GLP-1 RA treatment using semaglutide, nondiabetic status, and higher percentage of body fat might be associated with better weight reduction, 'basal metabolic rate, skeletal muscle mass, muscle mass of the abdomen and limbs, and serum creatinine were nonlinearly associated with the probability of successful weight reduction.' Randy Seeley, MD, Henry King Ransom Endowed Professor of Surgery, Internal Medicine, and Nutritional Sciences at the University of Michigan School of Medicine, Ann Arbor, Michigan, and director of the National Institutes of Health-funded Michigan Nutrition Obesity Research Center, told Medscape Medical News , 'The main results of the study agree with what the field has already seen. Although it is a relatively small study, it corroborates other larger studies,' said Seeley, who was not involved in the study. This work was supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project. Ji reported receiving fees for lecture presentations and for consulting from AstraZeneca, Merck, Metabasis, MSD, Novartis, Eli Lilly and Company, Roche, Sanofi-Aventis, and Takeda. Seeley reported that his lab has worked with both Novo and Lilly (and others trying to enter the space), and he has also served as a paid consultant for both of those companies (and others trying to enter the space).
Scientific American
01-07-2025
- Health
- Scientific American
Could China's New GLP-1 Drugs Beat Out Ozempic?
A drug that outperforms placebo in helping people to lose weight is one of a growing number of next-generation obesity drugs being produced in China. At first, Chinese pharmaceutical companies rushed to make similar versions of blockbuster weight-loss drugs, such as Wegovy and Ozempic, that have taken the world by storm. Nowadays, China is emerging as important innovator for new drug discovery in this field, says Daniel Drucker, an endocrinologist at the University of Toronto in Canada. Results from a phase III trial of ecnoglutide show that people receiving a weekly injection of the drug lost up to 13.8 kilograms over 48 weeks of treatment. By contrast, people given placebo injections lost around 200 grams. The results were published in The Lancet Diabetes and Endocrinology on 21 June. On supporting science journalism If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today. Ecnoglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist analogue, similar to the blockbuster obesity drug semaglutide. These drugs mimic the hormone GLP-1, which is involved in regulating appetite and managing blood-sugar levels. Unlike semaglutide, ecnoglutide preferentially targets the production of cyclic adenosine monophosphate, a messenger molecule associated with regulating glycogen, sugar and lipid metabolism, which helps to control blood-sugar levels, as well as weight loss. The study, funded by drug manufacturer Sciwind Biosciences, based in Hangzhou, China, included 664 people given either a weekly injection of a placebo, or one of three doses of ecnoglutide. At the maximum dose of 2.4 milligrams, 92.8% of people lost at least 5% of their body weight, compared with 14% of people receiving placebo injections. People receiving ecnoglutide were also able to maintain their reduced weight after stopping treatment, regaining around 1% of their body weight over a 7-week period. Linong Ji, a co-author and a diabetes researcher at Peking University People's Hospital in Beijing, says ecnoglutide also improved risk factors for heart disease and diabetes, and reduced the amount of fat in people's livers. More drugs to come Dozens of GLP-1 drugs are being developed and tested in China, with 'many more to come', says Drucker. Among them is mazdutide, which mimics GLP-1 and glucagon, a hormone involved in blood-sugar levels. In trial results published in May, a weekly injection helped more people to lose up to 15% of their body weight over 36 weeks and reduced the risk of cardiovascular diseases compared with a placebo treatment. Developed by Eli Lilly in Indianapolis, Indiana, mazdutide is manufactured by Innovent Biologics in Suzhou, China, under an exclusive licence. Other trials are testing whether the drug can treat sleep apnoea or type 2 diabetes. The growing number of new GLP-1 drugs target multiple pathways at the same time so will result in more-tailored treatments, says Sof Andrikopoulos, a diabetes researcher at the University of Melbourne. The next generation of drugs will target specific conditions associated with diabetes and obesity, such as sleep apnoea, fatty liver disease, chronic kidney disease and heart disease, he adds. 'It'll give us options and it will make personalized medicine in obesity and diabetes more accessible.' Triple threat Another drug being developed in China, known as UBT251, is a triple agonist, mimicking GLP-1, glucagon and another hormone called gastric inhibitory polypeptide (GIP), which is involved in fat metabolism. UBT251 is the first biweekly injectable GLP-1 medicine and is in the early stages of testing to achieve weight loss and treat chronic kidney disease, fatty liver disease and type 2 diabetes. In March, Hengqin-based manufacturer the United Laboratories entered into a US$2-billion deal with Danish firm Novo Nordisk, which developed semaglutide, giving Novo Nordisk exclusive rights to test and sell the drug outside the Chinese mainland, Hong Kong, Macau and Taiwan. Bofanglutide, developed by Gan & Lee Pharmaceuticals in Beijing, is another biweekly injectable treatment, but it targets only GLP-1. A phase II trial began enrolling US participants with obesity in March to test it against a placebo and tirzepatide — sold as Mounjaro and Zepbound by Eli Lilly. Andrikopoulos says it makes sense that China is developing these drugs. 'Obesity and diabetes are major problems in Asian populations in China and in India,' he says. Studies that recruit participants in China are also important for investigating the efficacy of GLP-1 drugs in Asian populations, which could reveal differences not observed in studies from Europe or the United States. A Hong Kong-based pharmaceutical company, Ascletis, is also investigating the benefit of once-daily oral drug, called ASC30, for weight loss. Early trial results show that participants lost 6% more of their body weight on the drug than with a placebo. The company has applied for permission from the US Food and Drug Administration to run a phase II trial. Novo Nordisk and Eli Lilly are also working on oral GLP-1 medicines.
Medscape
21-06-2025
- Health
- Medscape
Novel GLP-1 Agonist Promotes Safe and Effective Weight Loss
Ecnoglutide, a novel glucagon-like peptide-1 (GLP-1) receptor agonist, was significantly more effective than placebo for inducing weight loss in adults with overweight or obesity, based on data from more than 600 individuals, results of the SLIMMER trial showed. In addition, ecnoglutide significantly improved other key cardiometabolic risk factors including waist circumference, blood pressure, lipid profile, A1c, fasting glucose, insulin level, and uric acid, while concurrently reducing liver fat content, said study author Linong Ji, MD, of Peking University People's Hospital, Beijing, China. "These benefits position ecnoglutide as a compelling therapeutic strategy for managing clinical obesity, especially in the context of metabolic dysfunction and associated steatotic liver disease (MASLD)," he noted. The results of the phase 3 randomized trial were presented here at the American Diabetes Association (ADA) 85th Scientific Sessions and simultaneously published in The Lancet Diabetes & Endocrinology . The new drug is distinct from other GLP-1 receptor agonists in its ability to selectively induce production of cyclic adenosine monophosphate (cAMP). Unlike unbiased GLP-1 therapies, ecnoglutide selectively activates cAMP signaling pathways while minimizing β-arrestin recruitment, which may explain its enhanced effectiveness for body weight reduction and sustained metabolic effects, Ji said in an interview. Weight Loss at All Doses The researchers randomized 664 overweight and obese Chinese adults to a weekly dose of 1.2 mg, 1.8 mg, or 2.4 mg of ecnoglutide or to placebo. The coprimary endpoints were percentage change in body weight and proportion of individuals with a reduction of 5% or more in body weight after 40 weeks. The study population included adults aged 18-75 years with overweight or obesity, defined as a BMI of 28 kg/m² or higher, or 24 kg/m² or higher with at least one weight-related comorbidity (prediabetes, hypertension, hyperlipidemia, MASLD, obstructive sleep apnea syndrome, or weight-bearing joint pain), but without type 1 or 2 diabetes. The mean age of participants was 34.2 years, and half were female. Individuals in the ecnoglutide group had an average body weight loss of 9.1%, 10.9%, and 13.2% from baseline at 40 weeks at doses of 1.2 mg, 1.8 mg, and 2.4 mg, respectively, which was significantly greater at all dose levels than placebo (0.1%) ( P < 0.0001 vs placebo for all doses). In addition, significantly more patients in the ecnoglutide groups lost at least 5% of their body weight at week 40 compared to the placebo group (77%, 84%, 87%, and 16% in the 1.2-mg, 1.8-mg, 2.4-mg, and placebo groups, respectively). A key secondary efficacy endpoint was the percentage of individuals who achieved a body weight loss of at least 5% after 48 weeks; 78% to 93% of participants across the ecnoglutide groups achieved this endpoint, with the greatest changes at the higher doses. Ten individuals across the ecnoglutide groups discontinued the medication because of adverse events, the most common of which were mild-to-moderate gastrointestinal events. Treatment-emergent adverse events occurred in 93% of participants in each of the ecnoglutide groups and in 84% of the placebo group. Clinical Takeaways and Next Steps "Ecnoglutide not only represents a viable competitor in the GLP-1 analog market but also stands out with its potential to address the nonresponse limitations in obesity treatment while providing holistic metabolic benefits," Ji told Medscape Medical News . At least 10% of weight-loss patients fail to achieve clinically significant weight loss of at least 5%, he explained. Possible reasons for the lack of success include genetic polymorphisms, metabolic heterogeneity, treatment compliance, or differential receptor sensitivity, he noted. "Providing alternative treatment options with a high response rate is crucial for individuals nonresponsive to existing therapies," he said. The trial results mark a milestone in obesity therapeutics and are a significant achievement in weight management. "After 48 weeks of treatment, ecnoglutide achieved a 15.4% weight reduction, with 92.8% of patients attaining clinically meaningful weight loss," he emphasized. "Considering the high potency of ecnoglutide" and the safety data, "it might serve as a viable option for individuals who do not achieve sufficient weight reduction with existing GLP-1 receptor agonists at their approved doses or need to achieve a better reduction in body weight," he added. "I am confident and optimistic that we'll see more personalized treatment regimens for obesity." Looking ahead, patients in the ecnoglutide 1.8-mg and 2.4-mg groups continued to have weight loss at week 48 without reaching a plateau, indicating that even greater weight loss might be possible with extended ecnoglutide treatment in studies of longer duration, Ji told Medscape Medical News . "To confer the added clinical advantage, a study comparing the clinical effects of a biased GLP-1 analog with those of a pharmacokinetically-matched but balanced GLP-1 analog would be needed," he said. In an accompanying editorial, Tricia M-M Tan, PhD, of Imperial College, London, UK, wrote: "The development of biased GLP-1 receptor agonists has been met with enthusiasm from the pharmaceutical industry, but does this design feature really confer any added clinical advantage?" She agreed with Ji that a comparative study of "a biased GLP-1 analog with those of a pharmacokinetically-matched but balanced GLP-1 analog" is needed. "Only then will the clinical role of this design feature be clear," she said. However, "the clinical results from ecnoglutide are likely to be generalizable to other populations," given that the effects of GLP-1 analogs are similar when tested in patients of various ethnicities, she said, adding this may increase the global availability of GLP-1 treatments. Refining Molecules to Enhance Efficacy, Reduce Side Effects Although current therapies represent potent, effective options for obesity-modifying treatment, they have limitations, with heterogeneity of responses in terms of potency and tolerability, said Andrew Kraftson, MD, a specialist in endocrinology and internal medicine at the University of Michigan, Ann Arbor, in an interview. "Ecnoglutide continues the trend to refine these molecules to enhance efficacy and reduce side effects," he said. "When these types of peptides interact with cells, they activate certain receptors and generate a signal cascade that promotes the desired effects. However, the less specific the 'message', the less potent the signal. Additionally, side effects can be a result of the less-controlled message," he noted. As with tirzepatide, ecnoglutide was developed to produce a "biased" signal with the intent to provide greater control of the signal/message to increase the odds of weight control and reduce the odds of side effects, he explained. Although the current study was not a head-to-head comparison with other incretin mimetics, the similarity in weight loss efficacy to tirzepatide, a dual GLP-1/glucagon insulinotropic peptide agonist (GIP), was interesting and supports the biasing effect of the molecular manipulation as an effective strategy to refine incretin therapy, Kraftson told Medscape Medical News . From a clinical standpoint, the trend towards refining weight management therapy will benefit patients by expanding their options, said Kraftson. "It may also help us address the observed heterogeneity in clinical response we see in our patients and bring us closer to personalized medicine," he said. The current study's limitations, as acknowledged by the researchers, include the relatively short time period, small sample size, and lack of head-to-head comparison, said Kraftson. Additionally, the study differs from clinical practice in its dose escalation, he said. In practice, "we are not trying to get patients to a certain dose, we are trying to find the lowest, most tolerable, and sufficiently effective dose to achieve health goals; therefore, we may determine that dose titration needs to happen more slowly and/or that a low(er) dose may be sufficiently effective," he told Medscape Medical News . "The adverse event data for common gastrointestinal issues could potentially be better in clinical practice if mitigation strategies are employed," he said. "I would like to see future studies that go beyond finding the relative efficacy of doses to reporting on effective strategies for patient-dose matching."
Yahoo
26-05-2025
- Health
- Yahoo
Phase 3 Clinical Study of Mazdutide in Chinese Adults with Overweight or Obesity (GLORY-1) Published in The New England Journal of Medicine (NEJM)
SAN FRANCISCO and SUZHOU, China, May 26, 2025 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncologic, autoimmune, cardiovascular and metabolic, ophthalmologic and other major diseases, announces that the results of a Phase 3 clinical study of mazdutide , a dual glucagon (GCG)/glucagon-like peptide-1 (GLP-1) receptor agonist, in Chinese adults with overweight or obesity (GLORY-1) have been published in The New England Journal of Medicine (NEJM) with a related editorial [ The first authors of this paper are Professor Linong Ji from Peking University People's Hospital and Professor Jiang Hongwei from the First Affiliated Hospital of Henan University of Science and Technology. In addition, Professor Linong Ji and Dr. Lei Qian from Innovent Biologics, served as the co-corresponding authors. This marks the first time that a clinical study of mazdutide, the world's first dual GCG/GLP-1 receptor agonist submitted for marketing, has been featured in a top-tier, peer-reviewed medical journal. It is also the first time a clinical trial of an innovative metabolic and endocrine therapy developed in China has been published in NEJM, a milestone that highlights China's growing capabilities in drug development and biotechnology innovation. This publication is expected to contribute to the evolving global clinical guidelines for the treatment of overweight and obesity. Regarding this groundbreaking new study, Professors Vanita R. Aroda of Harvard Medical School and Brigham and Women's Hospital, Boston, and Leigh Perreault of the University of Colorado Anschutz Medical Campus jointly commented that the GLORY-1 trial reveals distinct characteristics in the Chinese population compared to Western populations. Specifically, younger individuals in China exhibit metabolic dysfunction at rates comparable to or even exceeding those in older Western populations. The dual GCG/GLP-1 receptor agonist therapy demonstrated not only significant reductions in body weight and BMI but also comprehensive improvements in obesity-associated systemic health risks. Moreover, they emphasized that obesity interventions in China must adopt differentiated strategies tailored to local population features, with a focus on liver health and lipid management. Given the earlier onset of obesity in China and its heavier societal burden, earlier intervention is critical—and yields greater long-term benefits. For emerging obesity therapies, the experts noted that pharmacological treatments are only one component of a broader strategy. They advocated for synergizing drug therapies with public health policies to build a comprehensive prevention and treatment system, addressing the global obesity epidemic more effectively. Mazdutide is expected to launch in China this year, with anticipated approvals for weight management and glycemic control. Recognized for its superior weight loss efficacy and comprehensive metabolic benefits, mazdutide has been ranked among FIERCE Pharma's 2025 Top 10 Most Anticipated Drugs. In the GLORY-1 study, a total of 610 participants with obesity (BMI ≥ 28 kg/m2) or overweight (24 kg/m2 ≤ BMI < 28 kg/m2) with at least one obesity-related comorbidity were enrolled and randomized to receive mazdutide 4 mg, 6 mg, or placebo, administered subcutaneously once weekly for 48 weeks. The co-primary endpoints were the percentage change in body weight from baseline and a weight reduction of ≥5% at week 32. At baseline, the mean weight was 87.2 kg, and the mean BMI was 31.1 kg/m 2. The study results showed that mazdutide significantly reduced body weight compared to placebo at both 4 mg and 6 mg doses. Based on the efficacy estimand, the mean percent change from baseline in body weight was −10.97%, −13.38%, and −0.24% at Week 32 and −12.05%, −14.84%, and −0.47% at Week 48 in the mazdutide 4 mg, 6 mg, and placebo groups, respectively. A total of 76.3% of participants in the mazdutide 4 mg group and 84.0% in the mazdutide 6 mg group had a weight reduction of ≥5% at week 32, compared with 10.9% in the placebo group; 37.0% of participants in the mazdutide 4 mg group and 50.6% in the mazdutide 6 mg group had a weight reduction of ≥15% at week 48, compared with 2.1% in the placebo group. The primary endpoint and all key secondary endpoints of the study showed statistically significant superiority to placebo with p-values < 0.001 (main results as follows).Efficacy Estimand1 Treatment-policy estimand2Mazdutide 4 mg (N=203) Mazdutide 6 mg (N=202) Placebo (N = 205) Mazdutide 4 mg (N=203) Mazdutide 6 mg (N=202) Placebo (N = 205) Co-primary endpoints (Week 32) Percent weight reduction −10.97% −13.38% −0.24% −10.09% −12.55% 0.45 % Achieved a weight reduction ≥5% 76.3 % 84.0 % 10.9 % 73.9 % 82.0 % 10.5 % Some key secondary endpoints (Week 48) Percent weight reduction −12.05% −14.84% −0.47% −11.00% −14.01% 0.30 % Achieved a weight reduction ≥5% 73.5 % 82.8 % 11.5 % 71.6 % 81.6 % 10.8 % Achieved a weight reduction ≥10% 55.2 % 67.9 % 2.9 % 53.5 % 66.7 % 2.6 % Achieved a weight reduction ≥15% 37.0 % 50.6 % 2.1 % 35.7 % 49.5 % 2.0 % Waist circumference reduction −9.48 cm −10.96 cm −1.48 cm −9.12 cm −10.72 cm −1.41 cm 1. Efficacy estimand aims to estimate the study treatment effect when participants adhered to the planned treatment regimen. 2. Treatment policy estimand aims to evaluate the efficacy regardless of intercurrent events (early discontinuation of study treatment and initiation of new anti-obesity medication or bariatric surgery). Mazdutide also significantly reduced blood pressure, blood lipids (total cholesterol, triglycerides, and low-density lipoprotein cholesterol), serum uric acid, transaminase levels, and other cardiovascular and metabolic indicators. In addition, mazdutide significantly reduced liver fat content. Among participants with baseline liver fat content ≥ 5%, the mean percent changes in liver fat content from baseline to week 48 were −63.26%, −73.18%, and +8.20% in the mazdutide 4 mg, 6 mg, and placebo groups, respectively; Among participants with baseline liver fat content ≥ 10%, the mean percent change from baseline in liver fat content to week 48 were −65.85%, −80.24%, and −5.27% in the mazdutide 4 mg, 6 mg, and placebo groups, respectively. Good overall safety and tolerability of mazdutide were reported. The overall safety profile of the mazdutide group was consistent with findings from previous studies of mazdutide and aligned with that of other GLP-1 receptor agonists. The most frequently reported treatment-emergent adverse events included nausea, diarrhea, and vomiting, which were mostly mild or moderate in severity. At Week 48, both the mean change from baseline in heart rate was 2.6 beats per minute in both the mazdutide 4 mg and 6 mg groups. There were no safety signals of increased cardiovascular risk observed throughout the study. Professor Linong Ji, the Leading Principal Investigator of the Study, Peking University People's Hospital, stated, "For decades, global obesity management guidelines have predominantly relied on data from Caucasian populations, resulting in limited applicability to Asian demographics. Meanwhile, China's overweight/obese population exhibits distinct clinical characteristics and therapeutic needs compared to Western populations, necessitating evidence-based weight management strategies specifically tailored for Chinese patients. For most Chinese patients with overweight or obesity, the recommended weight loss target should be 5%-15% reduction maintained over 3-6 months. Moderate-to-severe obesity patients may require more ambitious goals. The GLORY-1 study, conducted in Chinese populations aligned with these targets, demonstrated promising outcomes: mazdutide achieved >15% weight reduction in nearly half of participants, indicating its efficacy across people living with overweight to severe obesity. Published in The New England Journal of Medicine, the GLORY-1 study not only signifies international recognition of China's innovative research in endocrine-metabolic disorders but also underscores the pioneering innovation of Chinese biopharmaceutical industry. Mazdutide's successful development will accelerate domestic enterprises' strategic presence in obesity management, enabling comprehensive, personalized solutions for China's overweight/obese population throughout their treatment journey." Dr. Lei Qian from Innovent Biologics, stated, "Mazdutide is globally first dual GCG/GLP-1 receptor agonist to be approved soon. The publication of its pivotal study GLORY-1 in The New England Journal of Medicine marks a breakthrough in China's drug development in endocrine and metabolic diseases. The study provides robust, high-quality clinical evidence for treating overweight and obesity in Chinese adults and will undoubtedly influence future clinical guidelines, diagnostic criteria, and standards of care. This academic achievement also demonstrates the exceptional clinical research capabilities of Chinese investigators and the solid innovative R&D abilities of Innovent. With mazdutide's imminent approval in China, we look forward to offering an advanced therapeutic option to improve the health and quality of life of individuals living with overweight or obesity. As an innovative pharmaceutical company, Innovent has actively responded to and promoted the goal of 'Healthy China 2030' by advancing science-based weight management through strategic collaborations and cutting-edge medical achievements. " About Obesity China has the world's largest population of individuals with overweight or obesity[1], a trend that is likely to rise. Obesity is associated to multiple comorbidities, and is a major contributor to reduced life expectancy and quality of life. In 2019, overweight and obesity accounted for 11.1% of deaths from chronic non-communicable diseases in China, nearly doubling from 5.7% in 1990[2]. Despite the chronic nature of obesity and its need for long-term management, treatment options remain limited. While lifestyle interventions remains the cornerstone of treatment, many patients struggle to achieve or maintain meaningful weight reduction. This underscores the urgent need for safe, effective and sustainable pharmacological interventions. About Mazdutide (IBI362) Innovent entered into an exclusive license agreement with Eli Lilly and Company (Lilly) for the development and potential commercialization of OXM3 (also known as mazdutide), a GLP-1R and GCGR dual agonist, in China. As a mammalian oxyntomodulin (OXM) analogue, mazdutide may offer additional benefits beyond those of GLP-1 receptor agonists—such as promoting insulin secretion, lowering blood glucose and reducing body weight—by also activating the glucagon receptor to increase energy expenditure and improve hepatic fat metabolism. Mazdutide has demonstrated excellent weight loss and glucose-lowering effects in clinical studies. It has also shown benefits in reducing waist circumference, blood lipids, blood pressure, blood uric acid, liver enzymes, and liver fat content, as well as improving insulin sensitivity. Mazdutide currently has two NDAs accepted for review by NMPA, including: For chronic weight management in adults with overweight or obesity; For glycemia control in adults with type 2 diabetes. Mazdutide is currently being evaluated in six Phase 3 clinical studies, including: GLORY-1: A Phase 3 trial in Chinese participants with overweight or obesity. GLORY-2: A Phase 3 trial in Chinese participants with moderate-to-severe obesity. GLORY-3: A Phase 3 trial comparing mazdutide and semaglutide in Chinese participants with overweight/obesity and metabolic dysfunction-associated fatty liver disease (MAFLD). DREAMS-1: A Phase 3 trial in treatment-naïve Chinese patients with T2D. DREAMS-2: A Phase 3 trial comparing mazdutide and dulaglutide in Chinese T2D patients with inadequate glycemic control on oral antidiabetic drugs. DREAMS-3: A Phase 3 trial comparing mazdutide and semaglutide in Chinese patients with T2D and obesity. Among these, GLORY-1, DREAMS-1 and DREAMS-2 studies have all met their endpoints, and other studies are currently ongoing. In addition, several new clinical studies of mazdutide are planned, including: A Phase 3 trial in adolescents with obesity. A Phase 3 trial in Chinese participants with moderate-to-severe obstructive sleep apnea (OSA) and obesity. New studies in metabolic dysfunction-associated steatohepatitis (MASH) and heart failure with preserved ejection fraction (HFpEF). About Innovent Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 15 products in the market. It has 3 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 15 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, LG Chem and MD Anderson Cancer Center. Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit or follow Innovent on Facebook and LinkedIn. Statement: (1) Innovent does not recommend the use of any unapproved drug (s)/indication (s). (2) Ramucirumab (Cyramza) and Selpercatinib (Retsevmo) and Pirtobrutinib (Jaypirca) were developed by Eli Lilly and Company. Forward-looking statement This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions. Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect. References [1] Pan XF, Wang L, Pan A. Epidemiology and determinants of obesity in China. Lancet Diabetes Endocrinol 2021; 9: 373–92. [2] Institute for Health Metrics and Evaluation. Global Health Data Exchange. GBD results tool. (accessed Jan 10, 2021). View original content: SOURCE Innovent Biologics
Yahoo
26-05-2025
- Health
- Yahoo
Phase 3 Clinical Study of Mazdutide in Chinese Adults with Overweight or Obesity (GLORY-1) Published in The New England Journal of Medicine (NEJM)
SAN FRANCISCO and SUZHOU, China, May 26, 2025 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncologic, autoimmune, cardiovascular and metabolic, ophthalmologic and other major diseases, announces that the results of a Phase 3 clinical study of mazdutide , a dual glucagon (GCG)/glucagon-like peptide-1 (GLP-1) receptor agonist, in Chinese adults with overweight or obesity (GLORY-1) have been published in The New England Journal of Medicine (NEJM) with a related editorial [ The first authors of this paper are Professor Linong Ji from Peking University People's Hospital and Professor Jiang Hongwei from the First Affiliated Hospital of Henan University of Science and Technology. In addition, Professor Linong Ji and Dr. Lei Qian from Innovent Biologics, served as the co-corresponding authors. This marks the first time that a clinical study of mazdutide, the world's first dual GCG/GLP-1 receptor agonist submitted for marketing, has been featured in a top-tier, peer-reviewed medical journal. It is also the first time a clinical trial of an innovative metabolic and endocrine therapy developed in China has been published in NEJM, a milestone that highlights China's growing capabilities in drug development and biotechnology innovation. This publication is expected to contribute to the evolving global clinical guidelines for the treatment of overweight and obesity. Regarding this groundbreaking new study, Professors Vanita R. Aroda of Harvard Medical School and Brigham and Women's Hospital, Boston, and Leigh Perreault of the University of Colorado Anschutz Medical Campus jointly commented that the GLORY-1 trial reveals distinct characteristics in the Chinese population compared to Western populations. Specifically, younger individuals in China exhibit metabolic dysfunction at rates comparable to or even exceeding those in older Western populations. The dual GCG/GLP-1 receptor agonist therapy demonstrated not only significant reductions in body weight and BMI but also comprehensive improvements in obesity-associated systemic health risks. Moreover, they emphasized that obesity interventions in China must adopt differentiated strategies tailored to local population features, with a focus on liver health and lipid management. Given the earlier onset of obesity in China and its heavier societal burden, earlier intervention is critical—and yields greater long-term benefits. For emerging obesity therapies, the experts noted that pharmacological treatments are only one component of a broader strategy. They advocated for synergizing drug therapies with public health policies to build a comprehensive prevention and treatment system, addressing the global obesity epidemic more effectively. Mazdutide is expected to launch in China this year, with anticipated approvals for weight management and glycemic control. Recognized for its superior weight loss efficacy and comprehensive metabolic benefits, mazdutide has been ranked among FIERCE Pharma's 2025 Top 10 Most Anticipated Drugs. In the GLORY-1 study, a total of 610 participants with obesity (BMI ≥ 28 kg/m2) or overweight (24 kg/m2 ≤ BMI < 28 kg/m2) with at least one obesity-related comorbidity were enrolled and randomized to receive mazdutide 4 mg, 6 mg, or placebo, administered subcutaneously once weekly for 48 weeks. The co-primary endpoints were the percentage change in body weight from baseline and a weight reduction of ≥5% at week 32. At baseline, the mean weight was 87.2 kg, and the mean BMI was 31.1 kg/m 2. The study results showed that mazdutide significantly reduced body weight compared to placebo at both 4 mg and 6 mg doses. Based on the efficacy estimand, the mean percent change from baseline in body weight was −10.97%, −13.38%, and −0.24% at Week 32 and −12.05%, −14.84%, and −0.47% at Week 48 in the mazdutide 4 mg, 6 mg, and placebo groups, respectively. A total of 76.3% of participants in the mazdutide 4 mg group and 84.0% in the mazdutide 6 mg group had a weight reduction of ≥5% at week 32, compared with 10.9% in the placebo group; 37.0% of participants in the mazdutide 4 mg group and 50.6% in the mazdutide 6 mg group had a weight reduction of ≥15% at week 48, compared with 2.1% in the placebo group. The primary endpoint and all key secondary endpoints of the study showed statistically significant superiority to placebo with p-values < 0.001 (main results as follows).Efficacy Estimand1 Treatment-policy estimand2Mazdutide 4 mg (N=203) Mazdutide 6 mg (N=202) Placebo (N = 205) Mazdutide 4 mg (N=203) Mazdutide 6 mg (N=202) Placebo (N = 205) Co-primary endpoints (Week 32) Percent weight reduction −10.97% −13.38% −0.24% −10.09% −12.55% 0.45 % Achieved a weight reduction ≥5% 76.3 % 84.0 % 10.9 % 73.9 % 82.0 % 10.5 % Some key secondary endpoints (Week 48) Percent weight reduction −12.05% −14.84% −0.47% −11.00% −14.01% 0.30 % Achieved a weight reduction ≥5% 73.5 % 82.8 % 11.5 % 71.6 % 81.6 % 10.8 % Achieved a weight reduction ≥10% 55.2 % 67.9 % 2.9 % 53.5 % 66.7 % 2.6 % Achieved a weight reduction ≥15% 37.0 % 50.6 % 2.1 % 35.7 % 49.5 % 2.0 % Waist circumference reduction −9.48 cm −10.96 cm −1.48 cm −9.12 cm −10.72 cm −1.41 cm 1. Efficacy estimand aims to estimate the study treatment effect when participants adhered to the planned treatment regimen. 2. Treatment policy estimand aims to evaluate the efficacy regardless of intercurrent events (early discontinuation of study treatment and initiation of new anti-obesity medication or bariatric surgery). Mazdutide also significantly reduced blood pressure, blood lipids (total cholesterol, triglycerides, and low-density lipoprotein cholesterol), serum uric acid, transaminase levels, and other cardiovascular and metabolic indicators. In addition, mazdutide significantly reduced liver fat content. Among participants with baseline liver fat content ≥ 5%, the mean percent changes in liver fat content from baseline to week 48 were −63.26%, −73.18%, and +8.20% in the mazdutide 4 mg, 6 mg, and placebo groups, respectively; Among participants with baseline liver fat content ≥ 10%, the mean percent change from baseline in liver fat content to week 48 were −65.85%, −80.24%, and −5.27% in the mazdutide 4 mg, 6 mg, and placebo groups, respectively. Good overall safety and tolerability of mazdutide were reported. The overall safety profile of the mazdutide group was consistent with findings from previous studies of mazdutide and aligned with that of other GLP-1 receptor agonists. The most frequently reported treatment-emergent adverse events included nausea, diarrhea, and vomiting, which were mostly mild or moderate in severity. At Week 48, both the mean change from baseline in heart rate was 2.6 beats per minute in both the mazdutide 4 mg and 6 mg groups. There were no safety signals of increased cardiovascular risk observed throughout the study. Professor Linong Ji, the Leading Principal Investigator of the Study, Peking University People's Hospital, stated, "For decades, global obesity management guidelines have predominantly relied on data from Caucasian populations, resulting in limited applicability to Asian demographics. Meanwhile, China's overweight/obese population exhibits distinct clinical characteristics and therapeutic needs compared to Western populations, necessitating evidence-based weight management strategies specifically tailored for Chinese patients. For most Chinese patients with overweight or obesity, the recommended weight loss target should be 5%-15% reduction maintained over 3-6 months. Moderate-to-severe obesity patients may require more ambitious goals. The GLORY-1 study, conducted in Chinese populations aligned with these targets, demonstrated promising outcomes: mazdutide achieved >15% weight reduction in nearly half of participants, indicating its efficacy across people living with overweight to severe obesity. Published in The New England Journal of Medicine, the GLORY-1 study not only signifies international recognition of China's innovative research in endocrine-metabolic disorders but also underscores the pioneering innovation of Chinese biopharmaceutical industry. Mazdutide's successful development will accelerate domestic enterprises' strategic presence in obesity management, enabling comprehensive, personalized solutions for China's overweight/obese population throughout their treatment journey." Dr. Lei Qian from Innovent Biologics, stated, "Mazdutide is globally first dual GCG/GLP-1 receptor agonist to be approved soon. The publication of its pivotal study GLORY-1 in The New England Journal of Medicine marks a breakthrough in China's drug development in endocrine and metabolic diseases. The study provides robust, high-quality clinical evidence for treating overweight and obesity in Chinese adults and will undoubtedly influence future clinical guidelines, diagnostic criteria, and standards of care. This academic achievement also demonstrates the exceptional clinical research capabilities of Chinese investigators and the solid innovative R&D abilities of Innovent. With mazdutide's imminent approval in China, we look forward to offering an advanced therapeutic option to improve the health and quality of life of individuals living with overweight or obesity. As an innovative pharmaceutical company, Innovent has actively responded to and promoted the goal of 'Healthy China 2030' by advancing science-based weight management through strategic collaborations and cutting-edge medical achievements. " About Obesity China has the world's largest population of individuals with overweight or obesity[1], a trend that is likely to rise. Obesity is associated to multiple comorbidities, and is a major contributor to reduced life expectancy and quality of life. In 2019, overweight and obesity accounted for 11.1% of deaths from chronic non-communicable diseases in China, nearly doubling from 5.7% in 1990[2]. Despite the chronic nature of obesity and its need for long-term management, treatment options remain limited. While lifestyle interventions remains the cornerstone of treatment, many patients struggle to achieve or maintain meaningful weight reduction. This underscores the urgent need for safe, effective and sustainable pharmacological interventions. About Mazdutide (IBI362) Innovent entered into an exclusive license agreement with Eli Lilly and Company (Lilly) for the development and potential commercialization of OXM3 (also known as mazdutide), a GLP-1R and GCGR dual agonist, in China. As a mammalian oxyntomodulin (OXM) analogue, mazdutide may offer additional benefits beyond those of GLP-1 receptor agonists—such as promoting insulin secretion, lowering blood glucose and reducing body weight—by also activating the glucagon receptor to increase energy expenditure and improve hepatic fat metabolism. Mazdutide has demonstrated excellent weight loss and glucose-lowering effects in clinical studies. It has also shown benefits in reducing waist circumference, blood lipids, blood pressure, blood uric acid, liver enzymes, and liver fat content, as well as improving insulin sensitivity. Mazdutide currently has two NDAs accepted for review by NMPA, including: For chronic weight management in adults with overweight or obesity; For glycemia control in adults with type 2 diabetes. Mazdutide is currently being evaluated in six Phase 3 clinical studies, including: GLORY-1: A Phase 3 trial in Chinese participants with overweight or obesity. GLORY-2: A Phase 3 trial in Chinese participants with moderate-to-severe obesity. GLORY-3: A Phase 3 trial comparing mazdutide and semaglutide in Chinese participants with overweight/obesity and metabolic dysfunction-associated fatty liver disease (MAFLD). DREAMS-1: A Phase 3 trial in treatment-naïve Chinese patients with T2D. DREAMS-2: A Phase 3 trial comparing mazdutide and dulaglutide in Chinese T2D patients with inadequate glycemic control on oral antidiabetic drugs. DREAMS-3: A Phase 3 trial comparing mazdutide and semaglutide in Chinese patients with T2D and obesity. Among these, GLORY-1, DREAMS-1 and DREAMS-2 studies have all met their endpoints, and other studies are currently ongoing. In addition, several new clinical studies of mazdutide are planned, including: A Phase 3 trial in adolescents with obesity. A Phase 3 trial in Chinese participants with moderate-to-severe obstructive sleep apnea (OSA) and obesity. New studies in metabolic dysfunction-associated steatohepatitis (MASH) and heart failure with preserved ejection fraction (HFpEF). About Innovent Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 15 products in the market. It has 3 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 15 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, LG Chem and MD Anderson Cancer Center. Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit or follow Innovent on Facebook and LinkedIn. Statement: (1) Innovent does not recommend the use of any unapproved drug (s)/indication (s). (2) Ramucirumab (Cyramza) and Selpercatinib (Retsevmo) and Pirtobrutinib (Jaypirca) were developed by Eli Lilly and Company. Forward-looking statement This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions. Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect. References [1] Pan XF, Wang L, Pan A. Epidemiology and determinants of obesity in China. Lancet Diabetes Endocrinol 2021; 9: 373–92. [2] Institute for Health Metrics and Evaluation. Global Health Data Exchange. GBD results tool. (accessed Jan 10, 2021). View original content: SOURCE Innovent Biologics Sign in to access your portfolio
