Core Viewpoint - Obesity has become a global public health issue, with over 890 million adults classified as obese, accounting for 13% of the total population. The rise in obesity is linked to lifestyle changes and has increased the risk of chronic diseases such as cardiovascular issues. Traditional weight loss strategies of "eat less, move more" are often insufficient, leading to a growing interest in pharmacological interventions like the popular weight loss drug semaglutide, which suppresses appetite [7][12]. Group 1 - The World Health Organization reports that the number of obese adults has surpassed 890 million globally, representing 13% of the total population. This trend has been particularly pronounced over the past 40 years, with significant increases in countries like China [7]. - A new study published in the journal "Cell" reveals the discovery of a group of previously unknown neurons in the brains of mice that regulate appetite by sensing food intake and signaling when to stop eating through the secretion of cholecystokinin (CCK) [7][8]. - These neurons are located in the brainstem, a primitive and evolutionarily conserved area of the vertebrate brain, suggesting that similar mechanisms may exist in humans [8]. Group 2 - The newly discovered neurons differ fundamentally from previously known satiety-regulating neurons, as they can continuously track food information during digestion and integrate various hormonal signals to determine when to stop eating [8][10]. - In animal experiments, researchers used optogenetics to control the activity of these neurons, demonstrating that activating them led to slower eating and reduced food intake in mice [10]. - The study also found that GLP-1 receptor agonists, the active ingredient in popular weight loss drugs, can activate these neurons, while appetite-stimulating hormones decrease their activity, indicating their role in dynamically tracking the eating process [12].

Core Insights - The article discusses the impact of GLP-1 drugs, originally designed for diabetes treatment, on the American food industry, highlighting a shift towards smaller portion sizes and lower-priced meals as consumers experience reduced appetite [5][7]. Group 1: Industry Changes - The rise in GLP-1 drug usage has led to a transformation in dining preferences, with consumers favoring smaller, more affordable meal options [5]. - Restaurants, such as Clinton Hall in New York, have introduced mini meal options, like a mini burger set priced at $8, which has gained popularity among weight-conscious consumers [5]. - The restaurant owner noted that the initiative to offer smaller portions aims to reduce food waste and costs, reflecting a positive market response [5]. Group 2: Health and Cultural Implications - Approximately one in eight American adults is currently using GLP-1 drugs for weight loss, indicating a significant trend in obesity management [7]. - The World Health Organization recognizes GLP-1 therapy as a long-term treatment option for obesity, emphasizing the need for a holistic approach that includes diet and exercise [7]. - Experts suggest that the trend towards smaller meal portions represents a cultural shift back to more reasonable serving sizes, moving away from the "super-sized" mentality of the late 20th century [7].

Core Viewpoint - The article discusses the increasing popularity and accessibility of the weight loss drug Mounjaro, particularly in the UK, highlighting its effectiveness and the challenges faced in its distribution through the National Health Service (NHS) [5][6][7]. Group 1: Mounjaro Overview - Mounjaro, a weight loss drug, is gaining traction and is being privately sold in clinics and pharmacies [6]. - The NHS is gradually introducing Mounjaro, with a long-term plan that may take up to 12 years to meet patient demand [6][7]. - The drug is intended for individuals with a BMI over 35 and at least one obesity-related health issue, as per NICE guidelines [7]. Group 2: Patient Experiences - Alix Harvey, a 35-year-old marine biologist, reported a 25% weight loss and a decrease in BMI from 32 to 22 after using Mounjaro for six months, although she expressed concerns about weight rebound after stopping the drug [10][11]. - Jane Graham, a 60-year-old heart physiologist, is eager to use Mounjaro but is disappointed that her BMI of 30 disqualifies her from NHS coverage, fearing that waiting for treatment could be too late for her health [13][14]. - Paul, 53, and his wife have been using Mounjaro purchased from a private clinic, with his wife losing 5 stone (31.7 kg) since starting the treatment [16].

Core Viewpoint - The article discusses significant developments in the GLP-1 receptor agonist market, highlighting recent financing events and advancements in drug development aimed at obesity and type 2 diabetes treatment [4][6]. Group 1: Company Developments - On January 20, 2026, Gilead Sciences announced the selection of a new generation of monthly subcutaneous GLP-1R/GIPR/GCGR triple receptor agonists [4]. - On January 22, 2026, Jixing Pharmaceuticals completed a $287 million Series D financing round, focusing on the clinical development of its oral small molecule GLP-1 receptor agonist CX11 for obesity, overweight, and type 2 diabetes [4]. - The funds raised will support ongoing Phase II clinical trials for obesity and type 2 diabetes in the U.S. and prepare for subsequent Phase III trials [4]. Group 2: Product Insights - CX11 is an oral small molecule GLP-1 receptor agonist designed to provide a more convenient alternative to current injectable GLP-1 therapies [6]. - In December 2024, Jixing Pharmaceuticals acquired global rights (excluding China) to the CX11 project from Wenta Pharmaceutical, integrating it into their core pipeline [6]. - The CEO of Jixing Pharmaceuticals stated that this financing marks a significant milestone for the company, accelerating innovation in cardiovascular metabolic disease drug development and indicating a new phase of global growth [6]. Group 3: Investment Landscape - The financing round attracted notable international biopharmaceutical investors, including RTW Investments and Hengdian Capital, along with new investors such as SR One, TCGX, RA Capital Management, and others [6]. - This reflects a sustained interest from top-tier investors in the oral GLP-1 space, indicating confidence in the potential of these therapies [6].

Core Viewpoint - The article discusses the increasing regulatory scrutiny by the U.S. Congress on GLP-1 drugs and their production by Chinese biotechnology companies, driven by concerns over the safety and legality of these products entering the U.S. market [6][7][9]. Regulatory Concerns - U.S. Congressman Raja Krishnamoorthi has formally requested three Chinese biotech companies to provide detailed information regarding the production, labeling, and export of GLP-1 drugs, amid rising concerns about unregulated products entering the U.S. drug supply chain [6]. - The companies named include Chinese Peptide Company, Zhongtai Biochemical Co., Ltd., and Hubei JXBio Biotech, which are believed to produce semaglutide and tirzepatide that may bypass FDA regulations [6][7]. Patient Safety and Health Risks - Krishnamoorthi emphasized that drug safety is non-negotiable for millions of American patients relying on GLP-1 medications, warning that illegal manufacturing could expose patients to unstudied health risks and undermine the U.S. drug safety system [7]. - The FDA has received hundreds of adverse reaction reports related to illegal compounded GLP-1 drugs, with potential links to serious health issues, including gastrointestinal disorders and even death [7][8]. Supply Chain and Compliance Issues - Despite the FDA declaring an end to the supply shortage of semaglutide, Krishnamoorthi warned that the underground supply chain remains active, with Chinese GLP-1 products potentially entering the U.S. market through mislabeling and other evasive actions [8]. - The Congressman posed 13 specific questions to the companies regarding their production processes, customer lists, and compliance with U.S. regulations, indicating a thorough examination of the GLP-1 global supply chain [8][9]. Shift in Regulatory Focus - The regulatory focus is shifting from merely approving and pricing end drugs to scrutinizing cross-border manufacturing, raw material sources, and traceability, indicating a broader competition involving compliance capabilities and supply chain transparency [9].

Core Viewpoint - The article discusses a study published in The Lancet that examines the relationship between general and abdominal obesity, measured by BMI and waist-to-height ratio (WHtR), and hypertension across different global regions [6][8]. Group 1: Background - Obesity is typically assessed using Body Mass Index (BMI) and abdominal obesity index, with the article focusing on the relationship between BMI and WHtR in various global populations and quantifying differences in these metrics between hypertensive and non-hypertensive individuals [8]. Group 2: Methodology - The study collected public sample data on BMI, WHtR, and hypertension from 1990 to 2023 for the general population aged 20-64 across eight global regions. It visually compared the distribution of BMI and WHtR, calculated the Pearson correlation coefficients, and used mixed-effects linear regression models to assess WHtR differences at the same BMI levels [9]. Group 3: Results - The correlation coefficients between BMI and WHtR across different regions ranged from 0.76 to 0.89. After adjusting for age and BMI, South Asia had the highest average WHtR for both genders, followed by Latin America and the Caribbean, and Central Asia, Middle East, and North Africa. In contrast, Central and Eastern Europe had the lowest average WHtR [10]. - To match the WHtR levels of high-income Western populations, South Asian women would need to lower their average BMI by 2.79 kg/m², while South Asian men would need to lower theirs by 1.28 kg/m² [10]. - Hypertension prevalence increased with rising BMI and WHtR across all regions. The C-statistics and NRI values for models using either fat measurement indicator were nearly identical, ranging from 0.72 to 0.81 for C-statistics and 0.34 to 0.57 for NRI. The combined use of BMI and WHtR showed only slight improvement over using either indicator alone [12].

Core Viewpoint - Tirzepatide is a drug that has gained attention in diabetes treatment and weight management, mimicking the action of the natural GLP-1 hormone to regulate blood sugar levels, promote insulin secretion, suppress appetite, and delay gastric emptying [4][10]. Mechanism of Action and Clinical Advantages - Tirzepatide activates GIP/GLP-1 receptors, promoting insulin secretion when blood sugar rises, reducing glucagon release, delaying gastric emptying, and suppressing appetite, making it advantageous for treating type 2 diabetes and obesity [6][7][8][9][10]. Main Indications - **Type 2 Diabetes Patients**: Suitable for adults with poorly controlled blood sugar despite diet and exercise, especially those who are overweight or obese, as 67.7% of diabetes patients in China are overweight/obese [11][12]. - **Obesity Patients**: Effective for adults with a BMI ≥28 kg/m² or ≥24 kg/m² with at least one weight-related comorbidity [13][20]. Contraindications and Precautions - Not suitable for type 1 diabetes patients, those with diabetic ketoacidosis, severe gastrointestinal diseases, history of medullary thyroid carcinoma, pregnant or breastfeeding women, and patients with hypersensitivity [14][15][16][17]. Patient Characteristics Suitable for Tirzepatide - **Weight Management Needs**: Patients with a BMI ≥28 kg/m² or ≥24 kg/m² with comorbidities [20]. - **Blood Sugar Control Needs**: Patients with poorly controlled blood sugar on other medications [21]. - **Simplified Treatment Needs**: Patients preferring less frequent dosing [22][23]. - **Low Hypoglycemia Risk**: Suitable for elderly patients and those in high-risk occupations [24][25]. Adverse Reactions and Management Strategies - Common adverse reactions include gastrointestinal issues (nausea, vomiting, diarrhea) and injection site reactions [27][28]. Management strategies involve gradual dose escalation and dietary adjustments [30][31]. Combination Use with Other Medications - **With SGLT-2 Inhibitors**: Can improve blood sugar control and weight loss [33]. - **With Insulin**: Can reduce insulin dosage and mitigate weight gain associated with insulin [34][35]. Future Development Directions - **Oral Formulations**: Development of oral tirzepatide formulations to enhance patient options [36][37]. - **Applications in Specific Patient Populations**: Research on its use in obese patients with heart failure and obstructive sleep apnea [38][40]. - **Personalized Treatment**: Potential for genetic testing to identify suitable patients for tirzepatide [41][42]. Efficacy - Clinical studies show that tirzepatide can reduce HbA1c by an average of 2.37% and lead to an average weight loss of 10.3 kg in type 2 diabetes patients [43]. It is the first drug to achieve over 20% weight loss in obese patients in phase 3 trials [43]. Conclusion - Tirzepatide offers multiple metabolic benefits for treating type 2 diabetes and obesity, suitable for patients needing blood sugar and weight control, with attention to contraindications and personalized treatment [44].

Core Viewpoint - The article discusses the recent update by the Therapeutic Goods Administration (TGA) in Australia regarding the medication Tirzepatide, emphasizing the importance of safety guidelines for its use among women of childbearing age, particularly in relation to oral contraceptives [4][6]. Group 1: Medication Overview - Tirzepatide is a dual-target agonist for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), approved for treating type 2 diabetes (T2DM), long-term weight management, and metabolic-related diseases [4]. - It has rapidly become one of the fastest-growing innovative drugs globally in terms of prescription volume due to its significant efficacy in glucose reduction, weight loss, and metabolic improvement [4]. Group 2: Regulatory Changes - The TGA's update includes specific recommendations for women using Tirzepatide alongside oral contraceptives, advising the use of non-oral contraceptive methods or additional barrier methods during the first four weeks of treatment and after each dose increase [7]. - This update follows a systematic assessment by international regulatory bodies regarding the potential risks associated with the expanded use of GLP-1 receptor agonists, particularly concerning reproductive safety and pregnancy risks [6][7]. Group 3: Global Regulatory Trends - The TGA's decision reflects a broader trend in regulatory practices as GLP-1 drugs transition from being viewed primarily as weight loss medications to long-term chronic disease management tools, indicating a shift towards more refined risk management [7]. - As the user population expands, regulatory requirements concerning reproductive safety and long-term medication effects are expected to tighten and become more detailed in various countries [7].

Core Viewpoint - The article discusses the effectiveness of different metabolic weight loss surgeries for patients with severe obesity, specifically comparing Roux-en-Y gastric bypass, sleeve gastrectomy, and adjustable gastric banding, highlighting that Roux-en-Y is superior in weight loss and quality of life improvements [6][7][10]. Summary by Sections Study Overview - The By-Band-Sleeve study was conducted across 12 medical centers in the UK, focusing on the clinical efficacy and safety of three surgical methods for severe obesity [8]. - A total of 1,346 patients were recruited, with 405 undergoing Roux-en-Y, 342 sleeve gastrectomy, and 383 adjustable gastric banding after exclusions [8]. Weight Loss Outcomes - After three years, 68% of patients in the Roux-en-Y group lost over 50% of their body weight, compared to 41% in the sleeve gastrectomy group and 25% in the adjustable gastric banding group [10]. - The average weight loss was -26.8 kg for Roux-en-Y, -19.4 kg for sleeve gastrectomy, and 14.0 kg for adjustable gastric banding [11]. Quality of Life Improvements - The EQ-5D-5L scores indicated that Roux-en-Y and sleeve gastrectomy patients had significantly higher quality of life scores (0.72 and 0.68, respectively) compared to the adjustable gastric banding group (0.62) [10]. - The study established that Roux-en-Y and sleeve gastrectomy were superior to adjustable gastric banding in terms of both weight loss and quality of life [10]. Health Complications - Roux-en-Y gastric bypass showed the most significant improvement in obesity-related complications such as diabetes and dyslipidemia [10]. - The study reported a reduction in HbA1c levels and fasting blood glucose across all groups, with Roux-en-Y showing the best outcomes [11]. Safety Profile - A total of 1,651 adverse events were reported, with Roux-en-Y, sleeve gastrectomy, and adjustable gastric banding having annual adverse event rates of 6.0, 5.7, and 4.6, respectively [11]. - The study recommends prioritizing Roux-en-Y gastric bypass for severe obesity patients, with sleeve gastrectomy as an alternative if Roux-en-Y is not feasible [11].

Core Viewpoint - The article highlights the significant advancement of Goli Pharma in the development of ASC37, a next-generation GLP-1R/GIPR/GCGR tri-agonist peptide, which is set to enter clinical trials for obesity treatment in 2026, marking a key milestone in multi-target metabolic drug development [4][6]. Group 1: Drug Development and Characteristics - ASC37 has been developed using Goli's AI-assisted drug discovery platform and ultra-long-acting drug development platform, showing enhanced agonistic activity at GLP-1R, GIPR, and GCGR receptors, approximately 5 times, 4 times, and 4 times stronger than the leading candidate retatrutide, respectively [6]. - The drug's design allows for a significant extension of its apparent half-life, supporting monthly subcutaneous administration with a single injection volume of less than 1 mL, which is expected to improve patient compliance and reduce manufacturing costs [6][7]. - In non-human primate studies, ASC37 demonstrated an average apparent half-life of about 17 days, which is 7 times longer than that of retatrutide, indicating superior in vivo exposure maintenance capabilities [7]. Group 2: Therapeutic Applications and Combination Strategies - ASC37 is being developed for single-agent and combination therapies targeting obesity, diabetes, and metabolic dysfunction-related fatty liver disease (MASH), addressing high-burden chronic diseases [7]. - Goli plans to explore the synergistic effects of ASC37 in combination with another monthly subcutaneous amylin receptor agonist peptide, ASC36, aligning with the global trend of integrating multiple pathways in metabolic drug development [7]. Group 3: Technological Platforms and Industry Position - The AISBDD and ULAP platforms are foundational to Goli's continuous output of peptide pipelines, allowing for the design of various release rates for subcutaneous depot peptides, achieving a better balance between efficacy, safety, and patient experience [8]. - The advancement of ASC37 reflects the shift of Chinese innovative pharmaceutical companies from imitation to competitive participation in global markets, particularly in drug frequency, pharmacokinetics, and system engineering [8].