Recomendaciones de expertos acerca del uso de teduglutide en pacientes pediátricos con sindrome de intestino corto / Expert recommendations on the use of teduglutide in pediatric patients with short bowel syndrome

Resumen El síndrome de intestino corto es una entidad de baja incidencia en los pacientes pediátricos, pero se asocia con elevadas tasas de morbimortalidad. El abordaje de estos pacientes por un equipo interdisciplinario de expertos enfocados en la rehabilitación intestinal mejora los resultados a corto y a largo plazo. Entre los recursos disponibles para el tratamiento se incluye el teduglutide, un análogo del péptido similar al glucagón tipo 2 (GLP-2) elaborado mediante técnicas recombinantes. Por medio de la aplicación del método Delphi, a partir de la evidencia disponible y de la experiencia de los autores, se proponen recomendaciones para el uso de teduglutide, dirigidas a los profesionales de la salud que tratan a los pacientes pediátricos con síndrome de intestino corto, así como a las autoridades sanitarias.

Abstract Short bowel syndrome is a low-incidence disorder among pediatric patients, but it is associated with high morbidity and mortality rates. Management of these patients by an interdisciplinary team of experts focused on intestinal rehabilitation improves short- and long-term outcomes. Available resources for treatment include teduglutide, a glucagon-like peptide type 2 (GLP-2) analog made by recombinant techniques. Considering the available evi dence and the authors' experience, Delphi-based recommendations for the use of teduglutide are suggested for healthcare professionals who treat pediatric patients with short bowel syndrome, as well as for health authorities.

La semaglutida en el tratamiento de las personas con diabesidad / Semaglutide in the Treatment of Diabesity Individuals

Introducción: La semaglutida es un fármaco que contribuye a la liberación de insulina por el páncreas y a la supresión del apetito por lo que lo convierte en un importante candidato para ser usado en el tratamiento de la diabesidad. Objetivo: Describir el efecto de la semaglutida en el tratamiento de las personas con diabesidad. Métodos: Se revisó la literatura publicada en el período comprendido de enero-febrero de 2021. Las palabras clave utilizadas fueron obesidad; diabetes mellitus; diabesidad; semaglutida; análogo del péptido similar al glucagón tipo 1. Se utilizaron como motores de búsqueda las bases de datos de Google Académico, PubMed y SciELO. Se evaluaron diferentes trabajos de revisión, investigación y páginas web que tenían menos de 10 años de publicados en idioma español, portugués o inglés, y que por el título trataban el tema de estudio. Fueron excluidos los artículos que no abordaron la relación entre diabetes y obesidad, así como el tratamiento con análogos del péptido similar al glucagón tipo 1. Esto permitió la consulta de 84 artículos, de los cuales 59 fueron referenciados. Conclusiones: El empleo de semaglutida favorece una mejor evolución en paciente con diabesidad, como complemento de una dieta y una actividad física adecuada. Al optimizar el control glucémico, contribuir a la pérdida de peso y a la mejoraría de ciertas comorbilidades, entre ellas la salud cardiovascular(AU)

Introduction: Semaglutide is a drug that contributes to the release of insulin from the pancreas and suppresses appetite, which makes it an important candidate for treating diabesity. Objective: To describe the role of semaglutide in the treatment of diabesity individuals. Methods: The necessary information to write this article was obtained in the 2022 two-month period January-February. The keywords used were obesity; Mellitus diabetes; diabesity; semaglutide; type 1 glucagon-like peptide analogue. The search engines corresponding to the Google Scholar, PubMed and SciElO databases were used. Different review, research and web pages were evaluated, which in general were published no more than 10 years ago, in Spanish, Portuguese or English and which dealt with the subject of study by title. Articles that did not address the relationship between diabetes and obesity, as well as treatment with glucagon-like peptide 1 analogues, were excluded. This allowed the consultation of 84 articles, 59 of them were referenced. Conclusions: The use of semaglutide, as a complement to a diet and physical activity appropriate to the needs of patients with diabesity, brought about several effects that favor better evolution of this health problem, by optimizing glycemic control, contributing to the loss of weight and the improvement of certain comorbidities, including cardiovascular health(AU)

Effect of Modified Gegen Qinliantang on TGR5/cAMP/GLP-1 Signaling Pathway in Pancreatic Tissue of Type 2 Diabetes Mellitus db/db Mice / 中国实验方剂学杂志

ObjectiveTo discuss the effect of modified Gegen Qinliantang （MGQT） on blood glucose and lipids and Takeda G protein-coupled receptor 5 （TGR5）-related pathways in pancreatic tissue of obese type 2 diabetes mellitus （T2DM） mice. MethodA total of 10 male specific pathogen free （SPF） m/m mice （7 weeks old） and 50 male SPF （7 weeks old） were adaptively fed for one week in SPF laboratory. The m/m mice were included in the blank group. T2DM was induce d in the 50 db/db mice. The model mice were randomized into the model group， metformin group （0.2 g·kg-1）， high-dose， medium-dose， and low-dose （31.9， 19.1， 6.4 g·kg-1） MGQT groups， with 10 in each group， and the drug dose was10 mL·kg-1. The model group and the blank group received distilled water of the same volume. The administration lasted 12 weeks （once/day）. Fasting blood glucose （FBG） was detected regularly. After 12 weeks of administration， serum levels of glycated serum protein （GSP）， serum glucose （GLU）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected. Pathological changes in the pancreatic tissue were based on hematoxylin-eosin （HE） staining. Western blot was used to determine the protein expression of TGR5， protein kinase A （PKA）， phosphorylated （p）-PKA， cyclic-AMP response element binding protein （CREB）， p-CREB， proprotein convertase 1/3 （PC1/3）， and glucagon-like peptide-1 （GLP-1） in pancreatic tissues. The level of cyclic adenosine monophosphate （cAMP） in pancreatic tissue was determined by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the blank group， the model group had pathological changes in pancreatic tissue， high levels of FBG， GSP， GLU， TC， TG， and LDL-C （P<0.01）， low level of HDL-C （P<0.05）， low protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in pancreatic tissue （P<0.01）， and low content of cAMP in the pancreas （P<0.01）. Pancreatic tissue lesion in the treatment groups were milder than that in the model group. Both the high-dose MGQT and metformin can reduce the levels of FBG， GSP， GLU， TC， TG， and LDL-C in db/db mice （P<0.05， P<0.01） and increase the level of HDL-C （P<0.01）. Except the GLP-1 protein in the medium-dose MGQT group， the protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in the high-dose and medium-dose MGQT groups and the metformin group increased compared with that in the model group （P<0.05， P<0.01）. The content of cAMP in the pancreatic tissue of the high-dose and medium-dose MGQT groups and the metformin group was raised compared with that in model group （P<0.05， P<0.01）. ConclusionMGQT can improve the glucose homeostasis in db/db mice with T2DM by regulating TGR5/cAMP/GLP-1 signaling pathway-related protein expression.

Evaluation of monitoring on serum silent information regulator-related enzyme 3, glucagon-like peptide-1 and angiopoietin-like protein 4 in patients with acute ischemic stroke / 中国医师进修杂志

Objective:To investigate the value of monitoring on serum silent information regulator-related enzyme 3 (SIRT3), glucagon-like peptide-1 (GLP-1) and angiopoietin-like protein 4 (ANGPTL4) in patients with acute ischemic stroke (AIS).Methods:Eighty patients with AIS who treatment in Qiongzhong Li and Miao Autonomous County People′s Hospital from May 2019 to April 2022 were selected retrospectively as the observation group, and 60 healthy volunteers who underwent physical examination during the same period were selected as the normal control group. The levels of serum SIRT3, GLP-1, and ANGPTL4 between the two groups were compared. The neurological deficit degree of AIS patients was evaluated by National Institutes of Health Stroke Scale(NIHSS) and the correlation of SIRT3, GLP-1 and ANGPTL4 with neurological deficit degree were analyzed. The levels of serum SIRT3, GLP-1 and ANGPTL4 before and after treatment and their difference value were compared between different clinical outcome of AIS patients, the risk factors for poor clinical outcome of AIS patients were analyzed by Logistic regression analysis, the value of prediction was analyzed by receiver operating characteristic (ROC) curve.Results:The level of serum GLP-1 in the observation group was lower than that in the normal control group: (50.37 ± 5.69) nmol/L vs. (34.89 ± 4.26) nmol/L; and the levels of serum SIRT3 and ANGPTL4 in the observation group were higher than those in the normal control group: (50.37 ± 5.69) ng/L vs. (34.89 ± 4.26) ng/L, (15.07 ± 3.12) μg/L vs. (11.15 ± 2.63) μg/L, there were statistical differences ( P<0.05). The results of correlation analysis showed that the levels of serum SIRT3 and ANGPTL4 were positively correlated with the degree of neurological impairment in AIS patients( r = 0.631, 0.776, P<0.05), and the level of serum GLP-1 was negatively correlated with the degree of neurological impairment in AIS patients ( r = - 0.693, P<0.05). After treatment, 66 patients obtained good clinical outcome, the good outcome rate was 82.50%(66/80). The levels of serum SIRT3 and ANGPTL4 in the poor clinical outcome patients were higher than those in the good clinical outcome patients: (41.33 ± 4.74) ng/L vs. (37.82 ± 4.05) ng/L, (12.98 ± 2.17) μg/L vs. (11.69 ± 2.06) μg/L; the level of serum GLP-1 in the poor clinical outcome patients was lower than that in the good clinical outcome patients: (592.33 ± 98.44) nmol/L vs. (709.41 ± 125.31) nmol/L; the difference value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in the poor clinical outcome patients were lower than those in the good clinical outcome patients: (10.22 ± 2.05) ng/L vs. (12.31 ± 2.94) ng/L, (268.21 ± 70.12) nmol/L vs. (379.92 ± 85.33) nmol/L, (2.18 ± 0.65) μg/L vs. (3.36 ± 0.94) μg/L, there were statistical differences ( P<0.05). The results of Logistic regression analysis showed that differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment were all independent influencing factors of poor clinical outcome in patients with AIS ( P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in predicting poor clinical outcome were 0.701, 0.758 and 0.844, respectively, and had certain predictive value, the AUC of joint evaluation was the largest (0.912). Conclusions:The levels of serum SIRT3 and ANGPTL4 in patients with AIS are increased, and the level of serum GLP-1 is decreased, and they are related to the degree of neurological deficit. Clinical monitoring of their level changes is helpful for clinical evaluation of the clinical outcome of patients with AIS.

Design and oral hypoglycemic activity of novel oral hypoglycemic peptide ODA / 中国药科大学学报

@#Incretin promotes insulin secretion through a glucose-dependent mechanism, involving glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Therefore, their correspondingly specific receptors GLP-1R and GIPR are suitable targets for the treatment of type 2 diabetes. Based on the oral hypoglycemic peptide OHP2 designed by our team, we further designed a new oral hypoglycemic peptide, ODA to reduce glucose. Compared with OHP2, ODA exhibited better lipophilicity as well as the enhanced endocytosis and transcytosis in Caco-2 cells. In addition, ODA remained the ability to activate GLP-1R and enhanced the binding ability to GIPR. The hypoglycemic efficacy of the low-dose ODA (0.53 mg/kg) is comparable to that of OHP2 (1.06 mg/kg). These results indicated that ODA could be a new oral drug with potential for the treatment of type 2 diabetes.

The protective effects and underlying mechanisms of dapagliflozin on diabetes-induced testicular dysfunction / 亚洲男科学杂志(英文版)

Male diabetic individuals present a marked impairment in fertility; however, knowledge regarding the pathogenic mechanisms and therapeutic strategies is unsatisfactory. The new hypoglycemic drug dapagliflozin has shown certain benefits, such as decreasing the risk of cardiovascular and renal events in patients with diabetes. Even so, until now, the effects and underlying mechanisms of dapagliflozin on diabetic male infertility have awaited clarification. Here, we found that dapagliflozin lowered blood glucose levels, alleviated seminiferous tubule destruction, and increased sperm concentrations and motility in leptin receptor-deficient diabetic db/db mice. Moreover, the glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin (9-39) had no effect on glucose levels but reversed the protective effects of dapagliflozin on testicular structure and sperm quality in db/db mice. We also found that dapagliflozin inhibited the testicular apoptotic process by upregulating the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL2) and X-linked inhibitor of apoptosis protein (XIAP) and inhibiting oxidative stress by enhancing the antioxidant status, including total antioxidant capacity, total superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity, as well as decreasing the level of 4-hydroxynonenal (4-HNE). Exendin (9-39) administration partially reversed these effects. Furthermore, dapagliflozin upregulated the glucagon-like peptide-1 (GLP-1) level in plasma and GLP-1R expression by promoting AKT8 virus oncogene cellular homolog (Akt) phosphorylation in testicular tissue. Exendin (9-39) partially inhibited Akt phosphorylation. These results suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Our results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction.

The efficacy of liraglutide combined with intragastric balloon on weight loss

SUMMARY OBJECTIVE: Intragastric balloon placement is an effective method for weight reduction. The aim of this study was to evaluate the efficacy of combining liraglutide with intragastric balloon. METHODS: Initially, demographic data of patients such as age, gender, comorbid diseases, adverse events, initial weight, height, body mass index, percent body fat, and waist-hip ratio were collected. Weight, body mass index, percent body fat, and waist-hip ratio were measured in the second, third, fourth, fifth, and sixth months. Then, intragastric balloon was removed and liraglutide was stopped. RESULTS: A total of 50 patients were included in the study, of whom 28 (56%) were in Group A (intragastric balloon) and 22 (44%) were in Group B (plus liraglutide). Weight change at the time of balloon removal was higher in Group B [median weight change 13.8 (7.8 min to 16.8 max) versus 7.9 (4.8 min to 11.8 max); p<0.01]. When the weight, percent body fat, body mass index, and waist-hip ratio changes were compared according to gender, no significant difference was observed in the groups. Comorbid diseases were hypertension in 7 patients (4 in Group A and 3 in Group B) and diabetes in 9 patients (5 in Group A and 4 in Group B). No statistical significance was found. CONCLUSION: Liraglutide has benefits in terms of weight, percent body fat, and body mass index reduction when administered with intragastric balloon.

A New Study From Ivan de Araujo Lab Reported GLP-1 Mediated Gut-Brain Neural Circuit Controls Appetite Suppression / 中山大学学报(医学科学版)

A new study in Cell from Ivan de Araujo and colleagues reported that intestinal GLP-1 acts on an inter-organ sympathetic neural circuit that induces appetite suppression. This study revealed that GLP-1， secreted by ileal L cells， sensing by intestinal myenteric layer intestinofugal neurons activated a sympatho-gastro-spinal-reticular-hypothalamic pathway involved in appetite suppression， linking stomach distention to craniofacial programs for food rejection. These molecularly indentified， delimited enteric circuits may be targeted to ameliorate the abdominal bloating and loss of appetite typical of gastric motility disorders.

Mini health technology assessment of weekly preparations of glucagon-like peptide-1 receptor agonist / 中国药房

OBJECTIVE To comprehensively evaluate four weekly preparations of glucagon-like peptide-1 receptor agonist （GLP-1RA） marketed in China，and to provide evidence for hospitals to optimize drug catalogs and clinical rational drug use. METHODS Mini health technology assessment method was used to establish detailed evaluation rules according to A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions， and conduct comprehensive evaluation of four GLP- 1RA weekly preparations from aspects of pharmaceutical characteristics， effectiveness， safety， economy and other attributes. RESULTS Mini health technology assessment scores of the four GLP-1RA weekly preparations from high to low were dulaglutide 78.60 points， semaglutide 77.35 points，polyethylene glycol loxenatide 67.40 points， and exenatide microspheres 65.50 points， respectively. Dulaglutide had advantages in reducing blood sugar， arteriosclerotic cardiovascular disease， kidney benefits， and cost- effectiveness. Semaglutide had advantages in reducing blood sugar and weight loss， but its cost-effectiveness was lower than that of dulaglutide. Exenatide microspheres had advantages in the use of children， but its daily average treatment cost is the highest. Polyethylene glycol loxenatide needed further clinical evidence. CONCLUSIONS Four GLP-1RA weekly preparations all have high pharmaceutical comprehensive scores. Dulaglutide and semaglutide may have more comprehensive pharmaceutical value among them， while the use of exenatide microspheres for children is unique.

Medication guidelines for glucagon-like peptide-1 receptor agonist （2023 edition） / 中国药房

The prevalence of diabetes in China is increasing year by year， and has become a health issue of close concern to the whole society. Glucagon-like peptide-1 （GLP-1） receptor agonist （GLP-1RA）， as a new class of glucose-lowering drugs， is now widely used in the treatment of type 2 diabetes mellitus （T2DM） because of its significant glucose-lowering efficacy and low risk of hypoglycemia. As the level of evidence for its effects on improving cardiovascular system and renal protection and reducing body mass continues to improve， its status in the treatment guidelines for T2DM is gradually increasing. Currently， nine GLP-1RA drugs have been approved for the clinical treatment of T2DM in China. Although all of these drugs exert hypoglycemic effects based on the activation of GLP-1 receptors in the body， the differences in their own structures and natural GLP-1 amino acid homology lead to large differences in pharmacokinetic parameters and clinical efficacy among different analogs. In order to enable clinicians and pharmacists to have a full understanding of the characteristics and clinical evidence of these analogs and to better perform their therapeutic effects， Liaoning Provincial Pharmaceutical Society organized clinical medicine and pharmacy experts to develop a medication guide for nine GLP-1RA drugs to provide a reference for clinical medication needs and promote rational and standardized use by compiling and summarizing the pharmacological characteristics， clinical applications， adverse reactions， interactions， the medications in special populations and medication management.

Cinnamomi Cortex Regulates Incretin Effect in Diabetic Rats / 中国实验方剂学杂志

ObjectiveTo observe the pharmacodynamic effects of Cinnamomi Cortex on the incretin effect in the rat model of diabetes mellites （DM） induced by streptozotocin （STZ） and explore the underlying mechanism from glucagon-like peptide-1 （GLP-1） and dipeptidyl peptidase-4 （DPP-4）. MethodForty SD rats were randomly assigned into blank， model， sitagliptin （0.1 g·kg-1）， and low- and high-dose Cinnamomi Cortex （0.45 and 0.9 g·kg-1， respectively） groups. The DM rat model was established by a high-fat diet combined with intraperitoneal injection of 40 mg·kg-1 STZ in other groups except the blank group. The intervention lasted for 8 weeks. The status， body weight， water intake， food intake， and fasting blood glucose （FBG） of the rats were observed and determined. Hematoxylin-eosin staining was employed to reveal the pathological changes of the pancreas， and immunohistochemistry to detect the expression of glucagon in the pancreas. Biochemical assay was employed to measure the serum levels of lipid metabolism indexes such as total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL）. Enzyme-linked immunosorbent assay was employed to determine the levels of glycosylated hemoglobin， insulin， glucagon， GLP-1， and glucose-dependent insulinotropic polypeptide （GIP） in rat serum， and Western blot to determine the protein levels of GLP-1 and DPP-4 in the pancreas. ResultAfter 8 weeks of intervention， the model group showed higher body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and lower HDL， GLP-1， and GIP than the blank group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed lower body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and higher HDL， GLP-1， and GIP than the model group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed recovered morphology of islet cells and no nucleus aggregation. Compared with the model group， the Cinnamomi Cortex groups showed declined levels of glucagon in the center of islet cells. Compared with the blank group， the model group showed up-regulated protein level of DPP-4 and down-regulated protein level of GLP-1 （P<0.01）. Compared with the model group， the high-dose Cinnamomi Cortex groups showed down-regulated protein level of DPP-4 and up-regulated protein level of GLP-1 （P<0.05）. ConclusionCinnamomi Cortex may reduce blood glucose and improve incretin effect to lower the blood glucose level by regulating DPP-4 and GLP-1 in DM rats.

Progress in research on neuroprotective mechanism of glucagon-like peptide-1 receptor agonists and analogues in Parkinson's disease / 中国生物制品学杂志

@#Parkinson's disease(PD)is the second common neurodegenerative disease that mostly occurs in middle-aged and elderly people. Currently,Levodopa is the main first-line treatment drug,but the long-term efficacy of patients is not good,and even side effects such as“on-off”phenomenon and orthostatic hypotension occur. Glucagon-like peptide-1receptor agonists(GLP-1RA)and analogues are endogenous peptide hormones that can be released into the blood and enter the central nervous system to exert neuroprotection by crossing the blood-brain barrier. Numerous studies have shown that GLP-1RA can improve movement disorders and restore dopaminergic neuron activity in PD. However,the mechanism of GLP-1RA is not yet fully clear. This paper summarized the mechanism of GLP-1RA and its analogues in improving PD movement disorders and restoring dopaminergic neuron activity,and reviewed the aspects of reducing neuroinflammation,inhibiting oxidative stress,inhibiting apoptosis,regulating mitochondrial morphology,increasing neuronal protrusions,enhancing autophagy,and regulating intestinal flora homeostasis,so as to provide new ideas for research of the mechanisms of PD and development of GLP-1RA-related new drugs.

A cross-sectional study to assess beta-cell function in individuals with recently diagnosed young-onset type 2 diabetes mellitus and its’ complications / Journal of the ASEAN Federation of Endocrine Societies

Objective@#The primary objective was to assess beta-cell function of recently-diagnosed young-onset type 2 diabetes mellitus (T2DM) individuals using basal and stimulated C-peptide levels. The secondary objective was to examine the association between C-peptide with metabolic factors and diabetes complications.@*Methodology@#A cross-sectional study was conducted for young-onset T2DM individuals aged 18-35 years with a disease duration of not more than 5 years. Plasma C-peptide was measured before and after intravenous glucagon injection. Demographic data, medical history and complications were obtained from medical records and clinical assessment. Continuous data were expressed as median and interquartile range (IQR). Categorical variables were described as frequency or percentage. Multivariable linear regression analysis was used to determine factors associated with C-peptide levels.@*Results@#113 participants with young-onset T2DM with a median (IQR) age of 29.0 (9.5) years and 24 (36) months were included in this study. The median (IQR) basal and stimulated C-peptide was 619 (655) pmol/L and 1231 (1024) pmol/L. Adequate beta-cell function was present in 78-86% of the participants based on the basal and stimulated C-peptide levels. We found hypertension, obesity and diabetic kidney disease (DKD) to be independently associated with higher C–peptide levels. In contrast, females, smokers, those on insulin therapy and with longer duration of disease had lower C–peptide levels.@*Conclusion@#Most recently diagnosed young-onset T2DM have adequate beta-cell function. Elevated C-peptide levels associated with obesity, hypertension and diabetic kidney disease suggest insulin resistance as the key driving factor for complications.

Effect of Zuogui Jiangtang Tongmai Prescription on SCFAs/GPR43/GLP-1/GLP-1R Signaling Pathway in Rats with Diabetes Mellitus Complicated with Cerebral Infarction / 中国实验方剂学杂志

ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Tongmai prescription （ZJT） in the treatment of diabetes mellitus complicated with cerebral infarction （DM-CI） in rats based on the short-chain fatty acids （SCFAs）/G protein-coupled receptor 43 （GPR43）/glucagon-like peptide-1 （GLP-1）/GLP-1 receptor （GLP-1R） signaling pathway. MethodSixty SD rats were randomly divided into sham operation group， model group， low- and high-dose ZJT groups （12， 24 g·kg-1）， western medicine group （140 mg·kg-1 pioglitazone metformin tablets + 27 mg·kg-1 enteric-coated aspirin tablets）. Except for the sham operation group， all other groups were fed a high-sugar high-fat diet for 4 weeks and then subjected to intraperitoneal injection of 1% streptozotocin at 35 mg·kg-1 combined with middle cerebral artery occlusion （MCAO） to establish a DM-CI rat model. The corresponding interventions were performed with distilled water， low-dose ZJT， high-dose ZJT， pioglitazone metformin tablets， and enteric-coated aspirin tablets. After surgery， National Institutes of Health Stroke Scale （NIHSS） scoring and triphenyltetrazolium chloride （TTC） staining to measure the rat's cerebral infarct volume were carried out. Random blood glucose levels were measured， and hematoxylin-eosin （HE） staining was used to observe histopathological changes in rat brain tissues. Gas chromatography was employed to detect the content of SCFAs in the cecum contents. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure serum GLP-1 level. Western blot was used to detect the protein expression of GPR43 in rat ileal tissues and GLP-1R in the ischemic brain tissues. ResultCompared with the sham operation group， the model group showed significantly increased NIHSS scores， random blood glucose levels， and cerebral infarct volumes （P<0.01）， and significantly decreased SCFAs content， GLP-1 levels， and GPR43 and GLP-1R protein expression （P<0.01）. Compared with the model group， the high-dose ZJT group and the western medicine group exhibited significantly reduced NIHSS scores， random blood glucose levels， and cerebral infarct volumes （P<0.05， P<0.01）， and significantly increased SCFAs content， GLP-1 levels， and GPR43 and GLP-1R protein expression （P<0.01）. ConclusionZJT can improve glucose metabolism disorder and reduce neurological damage in DM-CI rats， and its mechanism may be related to the increase in SCFAs content and the upregulation of the GPR43/GLP-1/GLP-1R signaling pathway.

Effects of glucagon-like peptide-1 on male reproductive function / 中华内分泌代谢杂志

With the younger onset of diabetes, the reproductive dysfunction caused by diabetes has received widespread attention. Hyperglycemia and insulin resistance, the main features of diabetes, are high-risk factors for male reproductive dysfunction. Obesity, the common co-morbidity of diabetes, may aggravate the progression of reproductive dysfunction. Glucagon-like peptide-1(GLP-1) and its receptor agonists improve the overall health status by lowering blood glucose, reducing body weight, and inhibiting inflammatory response, which indirectly exerts protective effects on the reproductive system. GLP-1 also protects reproductive function by regulating the neuroendocrine function, and directly acting on the supporting cells and interstitial cells of the testis. However, some studies did not find the protective effects. High-quality clinical studies are needed. GLP-1 receptor agonists may be a therapeutic option to improve reproductive dysfunction in diabetic men.

Glucagon-like peptide-1 receptor agonists and glycemic management in non-critical hospitalized patients / 中华内分泌代谢杂志

In recent years, with the continuous development of glucagon-like peptide-1 receptor agonists(GLP-1RA), its role in the management of blood glucose in hospitalized patients has been explored. GLP-1RA can not only control blood glucose in non-critically ill hospitalized patients, but also inhibit appetite, delay gastric emptying, protect nerves, anti-inflammation, reduce systolic blood pressure and blood lipids. At the same time, many studies have found that it can also improve cardiovascular and renal outcomes and reduce the risk of hospitalization complications. Therefore, this paper analyzes the role of GLP-1RA in glycemic management by reviewing domestic and international studies, consensus and guidelines related to inpatient blood glucose management, and helps to better manage blood glucose of patients in non-critical care setting.

Relación entre el fármaco semaglutida y la reducción de peso en pacientes con obesidad: una revisión sistemática / Relation between the drug semaglutide and weight reduction in patients with obesity: a systematic review / Relação entre a droga semaglutida e a perda de peso em pacientes obesos: uma revisão sistemática

El tratamiento farmacológico para la obesidad es muy limitado, entre los existentes en el mercado, destaca la Semaglutida, ampolla subcutánea que se aplica semanalmente y se usa en pacientes con diabetes y obesidad. OBJETIVO: establecer la relación de Semaglutida como un potencial fármaco para el tratamiento de obesidad. MÉTODO: estudio de tipo descriptivo, principalmente enfocado en la revisión y análisis de investigaciones publicadas en bases de datos científicas de alta relevancia, restringiéndose únicamente a publicaciones del 2015 en adelante (2022) que engloben como tópico principal el uso de Semaglutida. RESULTADO: se identificaron 802 registros en las bases de datos, aplicando los criterios de selección se identificaron 45 artículos como potenciales fuentes de información, finalmente se seleccionaron 15 artículos con datos altamente relevantes para esta revisión, donde se consideró la dosis del fármaco para la reducción de peso se observa que a mayor cantidad de Semaglutida se obtiene una reducción significativa de peso, llegando a una media de 11.82 kg. CONCLUSIÓN: el tratamiento semanal con Semaglutida administrada a nivel subcutánea con cambios en el estilo de alimentación y actividad física, dan como resultados pérdida de peso sostenida en el tiempo clínicamente relevante, pudiendo llegar a la aplicabilidad en pacientes cuyo tratamiento por otros métodos más convencionales no es eficiente.

Pharmacological treatment for obesity is very limited; among those available on the market, Semaglutide, a subcutaneous ampoule applied weekly and used in patients with diabetes and obesity, stands out. OBJETIVE: to establish the relationship of Semaglutide as a potential drug for the treatment of obesity. METHOD: descriptive study, mainly focused on the review and analysis of research published in scientific databases of high relevance, restricting only to publications from 2015 onwards (2022) that include as main topic the use of Semaglutide. RESULT: 802 records were identified in the databases, applying the selection criteria 45 articles were identified as potential sources of information, finally 15 articles were selected with highly relevant data for this review, where the dose of the drug for weight reduction was considered, it is observed that the greater the amount of Semaglutide a significant weight reduction is obtained, reaching a mean of 11.82 kg. CONCLUSION: weekly treatment with Semaglutide administered subcutaneously with changes in eating style and physical activity, results in clinically relevant sustained weight loss over time, being able to reach applicability in patients whose treatment by other more conventional methods is not efficient.

Entre os tratamentos existentes no mercado, destaca-se Semaglutide, uma ampola subcutânea que é aplicada semanalmente e utilizada em pacientes com diabetes e obesidade. OBJETIVO: estabelecer a relação do Semaglutide como uma droga potencial para o tratamento da obesidade. METODO: estudo descritivo, focado principalmente na revisão e análise de pesquisas publicadas em bases de dados científicos altamente relevantes, restringindo-se apenas a publicações a partir de 2015 (2022) que incluem o uso do Semaglutide como tema principal. RESULTADOS: 802 registros foram identificados nos bancos de dados, aplicando os critérios de seleção 45 artigos foram identificados como fontes potenciais de informação, finalmente 15 artigos foram selecionados com dados altamente relevantes para esta revisão, onde a dose do medicamento para redução de peso foi considerada, observa-se que quanto maior a quantidade de Semaglutide uma redução de peso significativa é obtida, atingindo uma média de 11,82 kg. CONCLUSAO: o tratamento semanal com Semaglutide administrado subcutaneamente com mudanças na dieta e na atividade física resulta em perda de peso sustentada clinicamente relevante ao longo do tempo, e pode ser aplicável em pacientes cujo tratamento por outros métodos mais convencionais não é eficiente.

Revisão sobre o uso de inibidores de cotransportador sódio-glicose 2 e agonistas de peptídeo 1 em pessoas com diabetes mellitus tipo 2 e doença cardiovascular / Review on the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 agonists in people with type 2 diabetes mellitus and cardiovascular disease / Revisión sobre el uso de inhibidores del cotransportador de sodio-glucosa 2 y agonistas de péptido 1 similar al glucagón en personas con diabetes mellitus tipo 2 y enfermedad cardiovascular

Introdução: Introdução: Diabetes mellitus tipo 2 é um importante e crescente problema de saúde para todos os países. Objetivo: Este trabalho visa avaliar a qualidade da evidência disponível sobre os fármacos inibidores de sódio-glicose 2 e agonistas de glucagon 1 em pessoas com diabetes mellitus e doença cardiovascular aterosclerótica Métodos: Realizou-se revisão integrativa utilizando as bases de dados MEDLINE via PubMed, Embase via Cochrane Library, Cochrane Library, LILACS via BVS. A pergunta de pesquisa foi estruturada da seguinte forma: população ­ pessoas com diabetes mellitus tipo 2 e doença cardiovascular estabelecida; intervenção ­ tratamento usual exceto insulina + inibidores de sódio-glicose 2 ou tratamento usual exceto insulina + agonistas de glucagon 1; controle - tratamento usual exceto insulina + placebo; desfecho ­ mortalidade geral, mortalidade por causas cardiovasculares, morbidade, efeitos adversos. Resultados: Selecionaram-se dois estudos sobre empagliflozina. Esse medicamento associado ao tratamento usual foi superior ao placebo associado ao tratamento usual no desfecho primário (HR 0,86; IC95% 0,74­0,99; p=0,04), na redução de hospitalização por insuficiência cardíaca (HR 0,65; IC95% 0,50­0,85; p=0,002), da mortalidade cardiovascular (HR 0,62; IC95% 0,49­0,77) e da mortalidade geral (HR 0,68; IC95% 0,57­0,82; p<0,001). No subgrupo de pessoas com diabetes que não usavam insulina, houve benefício com empagliflozina em relação ao desfecho primário (HR 0,79; IC95% 0,64­0,97; DR 2,5; NNT 40) e a mortes de causa cardiovascular (HR 0,61; IC95% 0,44­0,85; DR 2; NNT 49). Houve heterogeneidade entre os subgrupos com benefício de empagliflozina no desfecho primário apenas para aqueles com idade ³65 anos (p=0,01) e hemoglobina glicada <8,5 (p=0,01). Em relação às mortes por causas cardiovasculares, houve diferença (p=0,05) com o uso de empagliflozina reduzindo o risco somente no subgrupo com índice de massa corporal <30. Não houve diferença significativa em relação ao placebo para acidente vascular encefálico fatal e não fatal, tampouco no desfecho composto de acidente vascular encefálico debilitante não fatal e acidente vascular encefálico fatal (HR 0,81; IC95% 0,43­1,50; p=0,50). Houve mais pessoas acometidas por acidente vascular encefálico no grupo intervenção em que a hemoglobina glicada inicial era ≥8,5%, favorecendo o placebo (p=0,01). Conclusões: Os dados encontrados favorecem o benefício de utilizar esse medicamento no Sistema Único de Saúde em pessoas com doenças cardiovasculares. Entretanto, houve heterogeneidade entre grupos populacionais, o que pode ajudar a delinear estratégias de uso para esses medicamentos. São necessários mais estudos para avaliar qual seria o motivo de não haver benefício em desfechos cerebrovasculares isoladamente.

Introduction: Introduction: Type 2 diabetes mellitus is an important and growing health problem worldwide. Objective: This study aims to evaluate the quality of the evidence available on sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 agonists in people with diabetes mellitus and atherosclerotic cardiovascular disease. Methods: This integrative review was performed using the following databases: MEDLINE via PubMed, Embase via Cochrane Library, Cochrane Library, LILACS via VHL. The research question was structured as follows: population ­ people with type 2 diabetes mellitus and established cardiovascular disease; intervention ­ usual treatment, except insulin + sodium-glucose cotransporter 2 inhibitors or usual treatment, except insulin + and glucagon-like peptide 1 agonists; control ­ usual treatment, except insulin + placebo; outcome ­ overall mortality, mortality from cardiovascular causes, morbidity, adverse effects. Results: Two studies on empagliflozin were selected. This drug associated with the usual treatment was superior to placebo associated with the usual treatment in the primary outcome (hazard ratio ­ HR 0.86; 95% confidence interval ­ 95%CI 0.74­0.99; p=0.04), in reducing heart failure hospitalization (HR 0.65; 95%CI 0.50­0.85; p=0.002), in cardiovascular mortality (HR 0.62; 95%CI 0.49­0.77), and in overall mortality (HR 0.68; 95%CI 0.57­0.82; p<0.001). The subgroup of people with diabetes who were not on insulin benefited from using empagliflozin concerning the primary outcome (HR 0.79; 95%CI 0.64­0.97; risk difference ­ RD 2.5; number needed to treat ­ NNT 40) and cardiovascular mortality (HR 0.61; 95%CI 0.44­0.85; RD 2; NNT 49). The analysis of the subgroups showed heterogeneity. Participants aged 65 years or older (p=0.01) and those with glycated hemoglobin lower than 8.5 benefited from empagliflozin in the primary outcome. A difference (p=0.05) related to cardiovascular mortality was found, with the use of empagliflozin reducing the risk only in the subgroup with body mass index <30. No significant difference was identified with respect to placebo for fatal and nonfatal stroke nor for the composite outcome of nonfatal disabling stroke and fatal stroke (HR 0.81; 95%CI 0.43­1.50; p=0.50). More people had strokes in the intervention group in which the initial glycated hemoglobin was ≥8.5%, favoring placebo (p=0.01). Conclusions: The data found suggest the benefit of the Brazilian public health system using this drug in people with cardiovascular diseases. However, the population groups were heterogeneous, which may help outline strategies for using these medications. Further studies are necessary to assess why isolated cerebrovascular outcomes showed no benefit.

Introducción: Diabetes mellitus tipo 2 es un importante y creciente problema de salud para todos los países. Objetivo: Este trabajo busca evaluar la calidad de la evidencia disponible sobre los fármacos Inhibidores del Cotransportador de Sodio-Glucosa 2 y agonistas de Péptido 1 similar al glucagón en personas con diabetes mellitus y enfermedad cardiovascular aterosclerótica. Métodos: Se realizó revisión integrativa utilizando las bases de datos MEDLINE vía PubMed, Embase vía Cochrane Library, Cochrane Library, LILACS vía BVS. La pregunta de investigación fue estructurada de la siguiente manera: población ­ personas con diabetes mellitus tipo 2 y enfermedad cardiovascular establecida; intervención ­ tratamiento usual excepto insulina + inhibidores de sodium-glucose cotransporter-2 o tratamiento usual excepto insulina + agonistas de Péptido 1 similar al glucagón; control ­ tratamiento habitual excepto insulina + placebo; desenlace ­ mortalidad general, mortalidad por causas cardiovasculares, morbilidad, efectos adversos. Resultados: Se seleccionaron dos estudios sobre empagliflozina. Este medicamento asociado al tratamiento habitual fue superior al placebo asociado al tratamiento usual en el resultado primario (HR 0.86; IC95% 0.74­0.99; p=0,04), en la reducción de hospitalización por insuficiencia cardíaca (HR 0.65; IC95% 0.50­0.85; p=0.002), de la mortalidad cardiovascular (HR 0,62; IC95% 0,49­0,77) y de la mortalidad general (HR 0,68; IC95% 0,57­0,82; p=0,001). En el subgrupo de personas con diabetes que no usaban insulina, hubo beneficio con empagliflozina con relación al desenlace primario (HR 0.79; IC95% 0.64­0.97; DR 2.5; NNT 40) y a muertes de causa cardiovascular (HR 0.61; IC95% 0.44­0.85; DR 2; NNT 49). No hubo diferencia significativa con relación al placebo para accidentes cerebrovasculares fatal y no fatal, tampoco en el resultado compuesto de accidente cerebrovascular debilitante no fatal y fatal (HR 0.81; IC95% 0.43­1.50; p=0.50). Hubo más personas acometidas por accidente cerebrovascular en el grupo intervención en que la hemoglobina glicada inicial era un 8,5%, favoreciendo el placebo (p=0.01). Conclusión: Los datos encontrados favorecen el beneficio de utilizar ese medicamento en el Sistema Único de Salud en personas con enfermedad cardiovascular. Entretanto ha habido heterogeneidad entre los grupos de población, lo que puede ayudar a delinear qué estrategias de uso para estos medicamentos. Son necesarios más estudios para evaluar cuál sería el motivo de no haber beneficio en resultados cerebrovasculares aisladamente.

Non-alcoholic fatty liver disease: Epidemiology, pathophysiology and an update on the therapeutic approaches

Non-alcoholic fatty liver disease (NAFLD) denotes a spectrum of fatty liver disease in individuals without significant alcohol consumption. NAFLD is set to be the most common etiology of serious liver diseases in numerous nations when accompanied by obesity and type 2 diabetes. It is further histologically categorized into the non-alcoholic fatty liver (NAFL; steatosis without hepatocellular injury) and non-alcoholic steatohepatitis (NASH) which is characterized by the coexistence of hepatic steatosis and inflammation and is accompanied by hepatocyte injury (ballooning), either with or without fibrosis. NAFL is considered the benign and reversible stage arising from the excessive accumulation of triglycerides in hepatocytes. However, NASH is a more progressive stage of NAFLD, due to the increased risks of evolving more serious diseases such as cirrhosis, hepatocellular carcinoma. This concept, however, has been lately challenged by a hypothesis of multiple parallel hits of NAFLD, in which steatosis and NASH are separate entities rather than two points of the NAFLD spectrum, not only from a set of histological patterns but also from a pathophysiological perspective. The current review highlights the epidemiology and pathophysiology of NAFLD, and its progression towards steatohepatitis, with special focus on the novel imminent therapeutic approaches targeting the molecular aspects and the pathogenic pathways involved in the development, and progression of NAFLD.

Efficacy and safety of Semaglutide for weight loss in obesity without Diabetes: A systematic review and meta-analysis / Journal of the ASEAN Federation of Endocrine Societies

Background@#The weight loss benefit of semaglutide in patients with diabetes is well-documented, but its clinical utility in treating obesity among patients without diabetes is less described. We therefore assessed the efficacy and safety of subcutaneous semaglutide as treatment for obesity in patients without diabetes.@*Methodology@#A comprehensive search of PubMed/MEDLINE, Cochrane and Google scholar was performed to identify trials on the efficacy and safety of subcutaneous semaglutide on patients with obesity without diabetes. Primary outcome was expressed as percent mean weight difference. Secondary outcomes including risk for gastrointestinal adverse events, discontinuation of treatment and serious adverse events were expressed as risk ratios. These were calculated using the random effects model.@*Results@#The study included 4 randomized controlled trials having a total of 3,613 individuals with obesity without diabetes. The mean difference for weight reduction was -11.85%, favoring semaglutide [95% confidence interval (CI) (-12.81,-10.90), p<0.00001]. Secondary outcomes showed that the risk of developing gastrointestinal adverse events was 1.59 times more likely with semaglutide (RR 1.59, 95%CI [1.34, 1.88], p<0.00001). Risk for discontinuation due to adverse events was twice as likely in the semaglutide group (RR 2.19, 95%CI [1.36,3.55], p=0.001) and the risk for serious adverse events was 1.6 times more likely for semaglutide (RR1.60, 95%CI [1.24, 2.07], p=0.0003). Serious events were mostly of gastrointestinal and hepatobiliary disorders such as acute pancreatitis and cholelithiasis.@*Conclusion@#Among individuals with obesity without type 2 diabetes, subcutaneous semaglutide is effective for weight loss with an 11.85% reduction from baseline compared to placebo. This supports the use of semaglutide for weight management in obesity. However, risk of gastrointestinal adverse events, discontinuation of treatment and serious adverse events were higher in the semaglutide group versus placebo.