International Journal of Molecular Medical Science 2025, Vol.15 http://medscipublisher.com/index.php/ijmms © 2025 MedSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. -
International Journal of Molecular Medical Science 2025, Vol.15 http://medscipublisher.com/index.php/ijmms © 2025 MedSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. MedSci Publisher is an international Open Access publisher specializing in disease therapy, clinical pharmacology, clinical biochemistry, vaccines, immunology, microbiology at the publishing platform that is operated by Sophia Publishing Group (SPG), founded in British Columbia of Canada. Publisher MedSci Publisher Editedby Editorial Team of International Journal of Molecular Medical Science Email: edit@ijmms.medscipublisher.com Website: http://medscipublisher.com/index.php/ijmms Address: 11388 Stevenston Hwy, PO Box 96016, Richmond, V7A 5J5, British Columbia Canada International Journal of Molecular Medical Science (ISSN 1927-6656) is an open access, peer reviewed journal published online by MedSci Publisher. The journal publishes scientific articles like original research articles, case reports, review articles, editorials, short communications and correspondence of the high quality pertinent to all aspects of human biology, pathophysiology and molecular medical science, including genomics, transcriptomics, proteomics, metabolomics of disease therapy, clinical pharmacology, clinical biochemistry, vaccines, immunology, microbiology, epidemiology, aging, cancer biology, infectious diseases, neurological diseases and myopathies, stem cells and regenerative medicine, vascular and cardiovascular biology, as well as the important implications for human health and clinical practice research. All the articles published in International Journal of Molecular Medical Science are Open Access, and are distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. MedSci Publisher uses CrossCheck service to identify academic plagiarism through the world’s leading plagiarism prevention tool, iParadigms, and to protect the original authors’ copyrights.
International Journal of Molecular Medical Science (online), 2025, Vol. 15, No. 6 ISSN 1927-6656 http://medscipublisher.com/index.php/ijmms © 2025 MedSci Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. Latest Content The Impact of GLP-1 Receptor Agonists on Weight Control in Patients with Diabetes and Comorbid Obesity JieWang International Journal of Molecular Medical Science, 2025, Vol. 15, No. 6, 253-262 Central Mechanisms of Inflammatory Cytokines in the Initiation and Progression of Metabolic Syndrome Liqin Guo, Jiayi Wu International Journal of Molecular Medical Science, 2025, Vol. 15, No. 6, 263-273 Association Between Treatment Failure Cases and Individual Genetic Background in Patients With Drug-Resistant Tuberculosis YanLou International Journal of Molecular Medical Science, 2025, Vol. 15, No. 6, 274-286 Mechanistic Research and Biomarker Characteristics of Immune Storms in Severe Dengue ManmanLi International Journal of Molecular Medical Science, 2025, Vol. 15, No. 6, 287-297 The Role of the Gut-Brain Axis in the Pathogenesis of Parkinson’s Disease and Its Clinical Application Prospects Jingqiang Wang International Journal of Molecular Medical Science, 2025, Vol. 15, No. 6, 298-309
International Journal of Molecular Medical Science, 2025, Vol.15, No.6, 253-262 http://medscipublisher.com/index.php/ijmms 253 Research Insight Open Access The Impact of GLP-1 Receptor Agonists on Weight Control in Patients with Diabetes and Comorbid Obesity JieWang Zhuji People’s Hospital, Zhuji, 311800, Zhejiang, China Corresponding email: 2308763906@qq.com International Journal of Molecular Medical Science, 2025, Vol.15, No.6 doi: 10.5376/ijmms.2025.15.0026 Received: 19 Aug., 2025 Accepted: 22 Sep., 2025 Published: 15 Nov., 2025 Copyright © 2025 Wang, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Wang J., 2025, The impact of GLP-1 receptor agonists on weight control in patients with diabetes and comorbid obesity, International Journal of Molecular Medical Science, 15(6): 253-262 (doi: 10.5376/ijmms.2025.15.0026) Abstract This study explored the application significance of GLP-1 receptor agonists (GLP-1 RAs) in the population with diabetes mellitus complicated with obesity. This type of drug achieves the dual effects of lowering blood sugar and losing weight through multiple mechanisms such as inhibiting central appetite, delaying gastric emptying, and improving metabolic status. Clinical studies have shown that GLP-1 RAs can lead to significant weight loss related to dosage and medication duration, and is superior to traditional hypoglycemic drugs that are prone to cause weight gain in terms of waist circumference and BMI. However, after discontinuing the medication, some patients may experience varying degrees of weight gain, suggesting that long-term management and lifestyle intervention are still necessary. In practical applications, individualized medication selection should be made based on BMI, comorbidities and cardiovascular risks, and a low-dose starting and gradually increasing dosage approach should be adopted to reduce gastrointestinal adverse reactions. When used in combination with insulin or sulfonylurea drugs, attention should also be paid to dose adjustment and hypoglycemic monitoring. Under the premise of reasonable patient screening, standardized titration and follow-up monitoring, GLP-1 RAs has a relatively ideal risk-benefit ratio and is expected to continue to be an important treatment method in the comprehensive management of diabetes mellitus complicated with obesity. Keywords GLP-1 receptor agonists (GLP-1 RAs); Diabetes mellitus complicated with obesity; Weight management / Weight loss; Glycemic control; Individualized treatment 1 Introduction Diabetes, especially type 2 diabetes, along with obesity, is a global health problem. The increasing number of such patients has also led to the situation of "diabetes combined with obesity", exerting considerable pressure on individual health, the medical system and social resources (Yao et al., 2024). When diabetes and obesity coexist, metabolic problems in the body become more severe, the risk of cardiovascular diseases increases, and it also affects the quality of life. Therefore, weight control has become an important part of treatment. It can not only help control blood sugar, but also reduce metabolic and cardiovascular-related risks (Popoviciu et al., 2023; Liu and Shu, 2025). Controlling blood sugar remains the core goal of diabetes treatment, but merely lowering blood sugar is difficult to solve a host of metabolic problems caused by diabetes combined with obesity. Appropriate weight loss not only helps improve blood sugar but also benefits blood pressure and blood lipid levels. However, due to factors such as physiology, habits and environment, most patients have difficulty maintaining an ideal weight all the time by merely controlling their diet and doing more exercise, and the overall effect is not very good (Popoviciu et al., 2023; Yao et al., 2024; Liu and Shu, 2025). Therefore, drugs that can both lower blood sugar and help lose weight have gradually become the focus of research and clinical attention. This study will analyze the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the treatment of diabetes mellitus complicated with obesity. This type of medicine can not only lower blood sugar but also assist in weight loss. Compared with traditional hypoglycemic drugs, it has a lower possibility of causing weight gain, and some drugs can even help patients maintain a low weight for a long time. GLP-1 RAs can help patients lose weight by 5% to 15%, significantly reduce glycated hemoglobin levels (HbA1c), and also has a protective effect on organs such as the heart and kidneys. In the future, such drugs are expected to play a more important role in the comprehensive treatment of diabetes complicated with obesity, helping patients maintain a healthy state for a long time and reducing the burden brought by the disease.
International Journal of Molecular Medical Science, 2025, Vol.15, No.6, 253-262 http://medscipublisher.com/index.php/ijmms 254 2 Disease Foundation and Management Challenges 2.1 Obesity with insulin resistance and chronic inflammation Obesity is a key factor causing insulin resistance and chronic low-grade inflammation, and insulin resistance and chronic low-grade inflammation are key causes of type 2 diabetes (Zatterale et al., 2020; Ahmed et al., 2021). When there is an excessive accumulation of adipose tissue (especially visceral fat), metabolism becomes more active, and inflammatory factors such as TNF-α and IL-6 are continuously released. These substances can interfere with the signal transmission of insulin and fail to function in the human body. Chronic inflammation related to obesity can affect multiple organ systems and is closely associated with the occurrence of cardiovascular diseases, non-alcoholic fatty liver disease and chronic kidney disease. These pathological changes superimpose on each other, continuously promoting blood sugar imbalance and increasing the risk of diabetic complications It is suggested that during the treatment of diabetes, attention should be paid simultaneously to the regulation of body weight status and inflammation level (Zatterale et al., 2020; Kojta et al., 2020). 2.2 The effect of lifestyle intervention is limited Adjusting diet and increasing physical activity are the main methods for diabetic obese patients to control their weight. These methods can help with weight loss and improve blood sugar in the short term, but many patients have difficulty adhering to them in the long term, and the actual effect is often underestimated (Kheniser et al., 2021; Meir et al., 2025). During the process of losing weight, the body will have automatic responses, such as reduced energy consumption and feeling hungry more easily, which leads to easy weight rebound and affects the long-term effect (Aronne et al., 2021; Petroni et al., 2021). Research has found that few people can maintain their weight loss effect in the long term merely by changing their lifestyle. Most patients' weight will gradually rebound and approach the pre-intervention level after reaching a certain stage of weight loss (Petroni et al., 2021; Meir et al., 2025). Weight regulation is influenced by multiple factors, including the body's own regulation, psychological state and the surrounding environment, etc. A single lifestyle intervention cannot meet the complex long-term management needs, so drug treatment or metabolic surgery is often regarded as an important supplement. 2.3 Some traditional hypoglycemic drugs may cause weight gain Some traditional hypoglycemic drugs, such as insulin and sulfonylurea drugs, although they can lower blood sugar, may cause weight gain during the medication process. This has led to some patients, although their blood sugar levels have improved, having more severe obesity problems and the difficulty of treatment has also increased accordingly. The GRADE study indicates that treatment regimens such as insulin glargine and glimepiride can better control blood sugar, but they also lead to more significant weight gain and increase the risk of hypoglycemia, cardiovascular and kidney diseases (Wexler et al., 2025). This therapeutic dilemma suggests that hypoglycemic strategies need to take into account the overall metabolic benefits and emphasize individualized plans. New-generation hypoglycemic drugs such as GLP-1 receptor agonists and SGLT2 inhibitors have neutral or weight-reducing effects while controlling blood sugar, which are more in line with the treatment needs of patients with diabetes complicated with obesity. Therefore, they have gradually been included in relevant guidelines and are recommended as preferred plans. 3 Overview and Clinical Localization of Three Types of GLP-1 RAs 3.1 Insulin therapy based on enterotropin glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of hypoglycemic drugs whose main function is to regulate insulin secretion, and their mode of action is similar to the physiological effect of natural GLP-1 in the body after eating. When blood sugar levels rise, such drugs can promote insulin secretion and inhibit the release of glucagon, thereby helping to control blood sugar levels. Because its effect is glycemic-dependent, the risk of hypoglycemia is relatively low when used alone.
International Journal of Molecular Medical Science, 2025, Vol.15, No.6, 253-262 http://medscipublisher.com/index.php/ijmms 255 Besides lowering blood sugar, GLP-1 RAs can also slow down stomach emptying and make people feel fuller by acting on the central nervous system, which helps control blood sugar and manage weight (Maple-Brown et al., 2022). The glucose-dependent hypoglycemic characteristics of GLP-1 RAs have obvious advantages in the treatment of type 2 diabetes (T2D), and can effectively reduce hyperglycemic levels without increasing the frequency of hypoglycemia. Its good safety and regulatory ability for multiple metabolic links have gradually made it an important component of the current diabetes drug treatment system (Hamed et al., 2024). 3.2 Preferred regimens for overweight or obese T2D patients For overweight or obese patients with type 2 diabetes, GLP-1 RAs is clinically important. Such drugs can usually reduce body weight and glycated hemoglobin (HbA1c) simultaneously (Hamed et al., 2024; Yao et al., 2024). Many clinical studies have shown that its weight loss effect is generally better than that of most traditional hypoglycemic drugs. Because GLP-1 RAs can manage both blood glucose and body weight simultaneously, it helps improve overall metabolism and reduce the risk of related complications (Wen et al., 2025). In current clinical practice guidelines, GLP-1 RAs is gradually recommended for the population with diabetes mellitus complicated with obesity, especially for patients requiring weight intervention or cardiovascular risk management (Wen et al., 2025). Some preparations are administered once a week. The administration frequency is low and the operation is simple, which is conducive to improving treatment compliance and supporting long-term standardized treatment (Maple-Brown et al., 2022). 3.3 Combined treatment strategy In clinical treatment, in order to improve metabolic status, GLP-1 RAs is often used in combination with other hypoglycemic drugs, among which metformin and SGLT2 inhibitors are the most common (Anderson, 2020; Gourdy et al., 2023). Metformin is a basic drug for treating type 2 diabetes, with stable effects and good safety. When used in combination with GLP-1 RAs, it can lead to better blood sugar control, contribute to weight loss, and the risk of hypoglycemia does not increase significantly (Maple-Brown et al., 2022). When GLP-1 RAs is used in combination with SGLT2 inhibitors, their modes of action complement each other, and a better superimposed effect can be produced in terms of weight control, blood pressure reduction and cardiovascular protection (Anderson, 2020). The study by Gourdy et al. (2023) pointed out that this combination regimen is helpful for patients with type 2 diabetes who have a higher risk of cardiovascular or kidney disease, or whose metabolic response is not good after monotherapy. Therefore, choosing an appropriate combination medication regimen based on the specific condition of the patient is a key approach to enhancing the therapeutic effect. 4 Weight Loss Mechanism 4.1 Enhance satiety and reduce food intake The weight loss effect of GLP-1 receptor agonists (GLP-1 RAs) is mainly related to the area of the brain that controls diet. When drugs pass through the bloodstream and stimulate the nerves in the brain, they activate specific receptors in the hypothalamus and brainstem that control the feelings of hunger and fullness. By altering neural signals, patients are more likely to feel full, have a reduced appetite and a decreased total food intake (Figure 1) (Bednarz et al., 2022; O Olukorode et al., 2024; Moiz et al., 2025). More in-depth research has found that such drugs can also affect the brain's reward system, making patients less likely to crave high-calorie foods and reducing the behavior of eating out of craving. This is very helpful for long-term weight control in patients with diabetes and obesity (Zhao et al., 2021; Fadel et al., 2025; Ilias et al., 2025; West et al., 2025). Different GLP-1 RAs can significantly inhibit appetite (Zhao et al., 2021; Moiz et al., 2025; Fadel et al., 2025). This effect is not only due to the slower gastric emptying, but more importantly, it directly affects the pathways in the brain that control diet. Patients usually feel fuller and less hungry when taking the medicine, which is consistent with the weight loss observed in clinical trials and actual use (Bednarz et al., 2022; O Olukorode et al., 2024; Ilias et al., 2025; West et al., 2025).
International Journal of Molecular Medical Science, 2025, Vol.15, No.6, 253-262 http://medscipublisher.com/index.php/ijmms 256 Figure 1 Alterations in the insulin receptor pathway, resulting from the activity of pro-inflammatory cytokines and androgens (Adopted from Bednarz et al., 2022) Image caption: Tumour necrosis factor α (TNF-α) affects insulin signaling by phosphorylation of serine in insulin receptor substrate-1 (IRS-1) through activation of several serine kinases, including c-Jun-NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). It inhibits insulin-induced tyrosine phosphorylation of IRS-1 and downregulates phosphoinositide 3-kinase (PI3K) activity; Decreased adiponectin concentration results in increased membrane sn-1,2-diacylglycerols (sn-1,2-DAGs) activity. It leads to impaired kinases activity and decreased insulin signaling; Testosterone induces insulin resistance in cells by affecting insulin-stimulated phosphorylation of protein kinase C (PKC); All these mechanisms contribute to decreased glucose transporter type 4 (GLUT-4) expression and decreased glucose transport into cells (Adopted from Bednarz et al., 2022) 4.2 Slow down gastric emptying and improve post-meal conditions GLP-1 RAs can also help with weight loss by influencing gastric activity. Mainly, it slows down the speed at which food enters the small intestine from the stomach, prolongs post-meal satiety, slows down glucose absorption, and makes post-meal blood glucose changes more stable (Zhao et al., 2021; Bednarz et al., 2022; Fadel et al., 2025). Generally, short-acting GLP-1 RAs inhibits gastric emptying more significantly and controls postprandial blood glucose better. Long-acting drugs are more often used to regulate fasting blood glucose and maintain overall blood glucose stability (Moiz et al., 2025). Slower gastric emptying can prolong the feeling of fullness and reduce snack and calorie intake between meals (Hamed et al., 2024; Ilias et al., 2025), but this is only an auxiliary effect. The main weight loss effect still comes from the brain's control of appetite (Zhao et al., 2021; Bednarz et al., 2022; Fadel et al., 2025). In addition, changes in gastric activity may increase the risk of gastrointestinal discomfort. Therefore, it is best to conduct an assessment before performing certain medical procedures or examinations (Urva et al., 2023; Nadeem et al., 2024). 4.3 Regulate glucagon and improve insulin resistance In addition to influencing eating and gastric activity, GLP-1 RAs is also involved in the body's metabolic regulation, helping to control weight and blood sugar. The research by O Olukorode et al. (2024) and Bednarze et al. (2024) mentioned that when blood sugar is high, it can prompt pancreatic β cells to secrete more insulin and prevent α cells from secreting excessive glucagon, thereby improving fasting and postprandial blood sugar. When glucagon levels decrease, the process of glucose production in the liver is inhibited, which is more pronounced in patients with type 2 diabetes (Hamed et al., 2024; Moiz et al., 2025; Fadel et al., 2025). Studies also suggest that GLP-1 RAs can enhance insulin sensitivity and reduce various chronic inflammatory indicators, such as C-reactive protein and interleukin-6, which are often elevated in obese and type 2 diabetic populations (Yao et al., 2024; Ren et al., 2025). Related metabolic improvements contribute to reducing visceral fat accumulation, optimizing lipid profiling and enhancing overall cardiometabolic health (Moiz et al., 2025;
International Journal of Molecular Medical Science, 2025, Vol.15, No.6, 253-262 http://medscipublisher.com/index.php/ijmms 257 Fadel et al., 2025; Ilias et al., 2025). Enables GLP-1 RAs to form synergistic effects at the levels of central regulation, gastrointestinal motility regulation and metabolic regulation, supporting its application advantages in weight management and long-term prognosis improvement in diabetes mellitus complicated with obesity. 5 Clinical Evidence: Impact on Weight Control 5.1 Relationship between weight loss and dosage as well as treatment duration Many clinical studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can significantly reduce the weight of patients with diabetes complicated with obesity. The more obvious the weight loss effect is usually associated with a larger dosage and a longer treatment duration (Figure 2) (Liu et al., 2023; Hamed et al., 2024). When using drugs for a long time, the weight loss effect of high-dose drugs such as semaglutide and ciceptide is more prominent. After more than one year of treatment, the average body weight decreased by approximately 13.9% and 17.8% respectively compared to the beginning (Xie et al., 2024; Moiz et al., 2025). Other studies have also observed similar situations, especially in patients who were initially overweight or had a longer medication duration, with more significant effects (Wong et al., 2025). Figure 2 Mechanism of action of GLP-1-RAs (Adopted from Hamed et al., 2024) The weight loss brought by GLP-1 RAs is not only significant in value, but mostly exceeds the 5% weight loss standard required for metabolic and cardiovascular benefits, and its practical application is clear (Yao et al., 2024). Although many GLP-1 drugs can help with weight loss, on the whole, the effects of drugs such as semaglutide and tipalatide may be better than those of illaglutide and exenatide (Liu et al., 2023; Zhang et al., 2025). Overall, this type of drug has good tolerance, and the main side effect is gastrointestinal discomfort (Iqbal et al., 2022; Wong et al., 2025). 5.2 Advantages over traditional hypoglycemic regimens Compared with traditional hypoglycemic methods, GLP-1 RAs has obvious advantages in controlling body weight and improving body shape (Yao et al., 2024). Meta-analysis and direct comparative studies have found that such drugs can significantly reduce body weight, waist circumference, and body mass index (BMI) associated with cardiometabolic risk (Xie et al., 2024). Studies have shown that the average waist circumference can be reduced by 4 to 17 centimeters. The higher the initial BMI or the longer the treatment duration, the more obvious the improvement (Liu et al., 2023; Wong et al., 2025). The above advantages are simultaneously reflected in blood glucose control and lipid profile improvement, differentiating GLP-1 RAs from the hyperglycemic hypoglycemic regimen in terms of overall metabolic benefits (Hamed et al., 2024). When weight management becomes the focus of treatment, this type of drug is often regarded as one of the important treatment options for patients with type 2 diabetes mellitus complicated with obesity. Existing studies support its use as a component of basic treatment to simultaneously improve metabolic indicators and body type-related outcomes (Yao et al., 2024; Wong et al., 2025). 5.3 Issues of weight maintenance and rebound after drug withdrawal Although GLP-1 drugs can help patients lose weight effectively during the treatment period, maintaining weight in the long term still faces challenges, especially after drug withdrawal. Several studies have shown that the weight of most patients will rebound to varying degrees after drug withdrawal, and the extent of rebound is
International Journal of Molecular Medical Science, 2025, Vol.15, No.6, 253-262 http://medscipublisher.com/index.php/ijmms 258 directly related to the extent of weight loss during treatment (Jensen et al., 2024). Take semaglutide or cticipatide as examples. Within one year of drug withdrawal, the patient's weight rebounded by approximately 75%, but was still lower than the pre-treatment level. This indicates that obesity is a chronic disease that requires long-term management (Berg et al., 2025; Budini et al., 2025). In terms of intervention strategies, maintaining weight without rebound requires a combination of medication and lifestyle adjustments, such as increasing physical activity. Jensen (2024) pointed out that this comprehensive approach can slow down the rate of weight rebound after drug withdrawal, and the weight loss effect of GLP-1 RAs is more obvious in the initial stage. Long-term effects rely on continuous personalized management and support to reduce the risk of rebound (Berg et al., 2025; Budini et al., 2025). Therefore, when using GLP-1 RAs to manage body weight, a long-term follow-up plan needs to be formulated and practical and sustainable treatment goals should be set. 6 Practical Treatment Strategies 6.1 Patient selection In clinical practice, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are more commonly used in overweight or obese patients with type 2 diabetes (T2D), especially those with significant weight concerns or those at high risk of cardiovascular disease with complications. Current guidelines and studies show that patients with a BMI of≥27 kg/m², especially those with concurrent hypertension, dyslipidemia or non-alcoholic fatty liver disease, have a better response to these drugs (Alfaris et al., 2024; Hamed et al., 2024). GLP-1 RAs is also applicable to patients with atherosclerotic cardiovascular disease or those at high risk of cardiovascular disease. Studies have confirmed that such drugs can reduce the risk of cardiovascular problems and contribute to the recovery of kidney function (Ussher and Drucker, 2023; Yao et al., 2024; Sheth et al., 2025). Patient screening is mainly based on individualized assessment and requires a comprehensive judgment based on previous medication response, hypoglycemia risk, patient preference, as well as weight status and comorbidities information (Alfaris et al., 2024). Patients who experienced weight gain or still failed to reach the target blood glucose level after insulin or sulfonylurea treatment were often given priority in the consideration of GLP-1 RAs, which was associated with a higher risk of weight gain and hypoglycemia with traditional regimens (Hamed et al., 2024; Yao et al., 2024). Patients with obesity-related problems such as obstructive sleep apnea and fatty liver are more suitable for incorporating GLP-1 RAs into the overall management plan (Popoviciu et al., 2023; Sheth et al., 2025). The rationality of population selection directly affects the presentation of therapeutic effect and the control of medication risk. 6.2 Administration method The treatment of GLP-1 RA usually adopts the dose-titration method, that is, starting with a low dose and gradually increasing the dose to improve patient tolerance and reduce gastrointestinal adverse reactions. Nausea, vomiting and diarrhea often occur in the early stage of treatment or when the dose is increased rapidly (Hamed et al., 2024). In clinical practice, it is generally started from the lowest recommended dose and the dose is gradually adjusted within 1 to 2 weeks to enable patients to gradually adapt to the drug effect, thereby reducing the risk of treatment interruption due to discomfort (Madsbad and Holst, 2025). Gradually adjusting the dosage can help patients develop the habit of taking medicine on time for a long time. Tell the patient that if any symptoms occur, they should consult a doctor immediately. If the reaction is mild, there are corresponding solutions (Yao et al., 2024). Some patients may need a relatively long time to find the appropriate dosage during treatment, or adjust the dosage regularly to ensure correct medication. Formulating treatment plans based on the patient's condition can make the patient more willing to take medicine and help stabilize blood sugar and control weight (Alfaris et al., 2024). 6.3 Joint processing and plan adjustment When GLP-1 RAs is used in combination with insulin or sulfonylurea drugs, it is usually necessary to reduce the dosage of other hypoglycemic drugs. This approach is more effective and can also reduce the risk of
International Journal of Molecular Medical Science, 2025, Vol.15, No.6, 253-262 http://medscipublisher.com/index.php/ijmms 259 hypoglycemia. GLP-1 RAs only functions when blood sugar is high (glucose-dependent), so the risk of hypoglycemia is relatively low when used alone. However, when used in combination with insulin or sulfonylureas (drugs that stimulate insulin secretion), the risk of hypoglycemia may increase. Clinical guidelines recommend that when GLP-1 RAs is initially used, the dosage of sulfonylureas or insulin should be appropriately reduced, especially in patients with blood glucose close to the target value (Hamed et al., 2024). After combined medication, the doctor or the patient themselves should measure blood sugar multiple times. At the same time, the doctor should teach the patient to identify hypoglycemic symptoms and coping methods. Some patients can gradually adjust the original medication regimen and reduce the total dosage of insulin after using GLP-1 RAs. This contributes to better weight loss and improved metabolic function (Yao et al., 2024). Patients who receive combined therapy should be followed up regularly, and their medication should be adjusted according to their individual conditions to ensure that blood sugar control, weight management and medication safety all meet the standards. 7 Safety and Conclusion The most common side effect in the treatment with GLP-1 receptor agonists (GLP-1 RA) is gastrointestinal problems, which are specifically manifested as nausea, vomiting, diarrhea or constipation. These reactions usually occur at the beginning of taking medicine or when the dosage is large. If it is more serious, it may prevent the patient from continuing to take the medicine. Gradually increasing the dosage and frequently informing patients of precautions are the main ways to alleviate discomfort and enhance their tolerance. It is necessary to tell the patient that adjusting their diet can relieve these symptoms. If they feel uncomfortable and it doesn't get better, they should speak up immediately. It should also be noted that most gastrointestinal reactions will gradually improve as the duration of taking the medicine increases. By adopting a more proactive management approach, doctors can help patients adhere to their medication and enjoy more stable metabolic benefits. Although GLP-1 RAs has a relatively low risk of hypoglycemia due to its glucose-dependent mechanism, the risk of hypoglycemia increases when used in combination with insulin or sulfonylurea drugs. At this point, closer blood glucose monitoring is required, and the dosage of other hypoglycemic drugs should be adjusted as the situation requires to reduce the occurrence of hypoglycemia. On the other hand, if gastrointestinal reactions persist for a long time, it may cause dehydration or electrolyte imbalance. Elderly people or those with poor kidney function need to pay more attention. Clinically, attention should be paid to dehydration manifestations such as reduced urine output and orthostatic hypotension, and electrolyte levels should be evaluated when necessary. It is also necessary to guide patients to ensure they drink plenty of water and identify in which situations they need to seek medical attention promptly. Overall, the value of GLP-1 receptor agonists in the population with type 2 diabetes mellitus complicated with obesity is clear, and they can simultaneously improve blood glucose and body weight. Their potential benefits in cardiovascular and renal aspects also support their use in the long-term comprehensive management of high-risk populations. Although safety issues such as gastrointestinal discomfort need to be managed in a standardized manner, under the premise of reasonable patient screening, sequential dosage increase and good monitoring, the overall benefits of GLP-1 RAs are usually greater than the risks. With the continuous increase in research, GLP-1 RAs is likely to continue to be one of the important drugs for the management of metabolic diseases, helping to improve the outcomes of patients with diabetes and obesity. Acknowledgments The author extends sincere thanks to Mr. Zhang for his feedback on the manuscript. Conflict of Interest Disclosure The author affirms that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Ahmed B., Sultana R., and Greene M., 2021, Adipose tissue and insulin resistance in obese, Biomedicine and Pharmacotherapy, 137: 111315. https://doi.org/10.1016/j.biopha.2021.111315
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International Journal of Molecular Medical Science, 2025, Vol.15, No.6, 263-273 http://medscipublisher.com/index.php/ijmms 263 Research Insight Open Access Central Mechanisms of Inflammatory Cytokines in the Initiation and Progression of Metabolic Syndrome Liqin Guo, Jiayi Wu Biotechnology Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China Corresponding author: jiayi.wu@cuixi.org International Journal of Molecular Medical Science, 2025, Vol.15, No.6 doi: 10.5376/ijmms.2025.15.0027 Received: 02 Sep., 2025 Accepted: 05 Oct., 2025 Published: 22 Nov., 2025 Copyright © 2025 Guo and Wu, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Guo L.Q., and Wu J.Y., 2025, Central mechanisms of inflammatory cytokines in the initiation and progression of metabolic syndrome, International Journal of Molecular Medical Science, 15(6): 263-273 (doi: 10.5376/ijmms.2025.15.0027) Abstract This study explored the central-related mechanisms of inflammatory cytokines in the occurrence and development of metabolic syndrome, analyzed the way peripheral inflammatory signals enter the center, the inflammatory response in the hypothalamus, and the participation of glial cells. It also investigated the key central pathways through which inflammatory cytokines affect metabolic regulation and the specific process by which central inflammation promotes the progression of metabolic syndrome. Based on the relevant evidence from animal experiments, human studies and intervention studies, the core role of central inflammatory cytokines was clarified, and the therapeutic methods targeting the central inflammatory pathway and future research directions were prospected. This study aims to provide a basis for understanding the pathogenesis of metabolic syndrome and developing new therapeutic measures. Keywords Metabolic syndrome; Inflammatory cytokines; Central inflammation; Hypothalamus; Insulin resistance 1 Introduction Metabolic syndrome (MetS) is a disease characterized by multiple metabolic abnormalities, with its core manifestations being excessive abdominal fat, insulin resistance, dyslipidemia, hypertension and poor blood sugar regulation. These manifestations can serve as diagnostic criteria and will significantly increase the risk of type 2 diabetes, cardiovascular diseases and other conditions. In the past decade, sedentary lifestyle, overnutrition and genetic factors have led to a rapid increase in the prevalence of MetS, affecting a large number of adults and adolescents worldwide (Fahed et al., 2022; Islam et al., 2024), becoming a public health issue that requires high attention (Rossi et al., 2021). The typical feature of MetS is chronic mild inflammation ("meta-inflammation"), which is different from acute inflammation (such as Fahed, etc.). This persistent inflammation is mainly caused by the dysfunction of adipose tissue. Adipose tissue secretes pro-inflammatory factors such as TNF-α and IL-6, attracting immune cells to aggregate and transform into a pro-inflammatory state, thereby aggravating systemic inflammation (Islam et al., 2024). This is key to the occurrence of MetS and related complications (Rossi et al., 2024). This study will explore the core issue of the peripheral inflammatory mechanism of MetS: how the brain perceives and integrates peripheral inflammatory signals to regulate metabolic balance or trigger diseases. Pro-inflammatory factors can transmit signals to the central nervous system through pathways such as the blood-brain barrier, activating immune cells like microglia. The resulting central inflammation can disrupt the neural circuits in the hypothalamus that regulate appetite and blood sugar, creating a vicious cycle of metabolic disorders. Clarifying the core mechanism by which inflammatory factors regulate metabolism-related neural regulation is of great significance for formulating new treatment strategies and breaking the mutually reinforcing cycle between inflammation and metabolic diseases. 2 Overview of Inflammatory Cytokines 2.1 Key pro-inflammatory factors Pro-inflammatory factors are important regulatory factors for the occurrence and development of metabolic syndrome, and they form chronic low-grade inflammation by promoting insulin resistance and metabolic
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