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BACKGROUND:Studies have found that glucagon-like peptide-1 and its analogues have a significant neuroprotective effect,and some drugs have been applied to the clinical stage Ⅲ study of Alzheimer's disease.However,the mechanism of its neuroprotective effect is still unclear,which needs to be further explored and clarified. OBJECTIVE:To screen out the genes related to the pathogenesis of Alzheimer's disease and the related targets of semaglutide for the treatment of Alzheimer's disease based on bioinformatics and network pharmacology analyses,to identify the potential target genes by comprehensive analysis of the two and to verify them at the cellular level. METHODS:Using DisGeNET database,differentially expressed genes between Alzheimer's disease patients and healthy population were screened out.The chemical structure formula and two-dimensional structure diagram of semaglutide were obtained using PubChem online database.GO/KEGG enrichment analysis was performed using DAVID online database.A protein-protein interaction network was constructed by using the STRING database.The HPA database was used to determine the distribution characteristics of the target proteins in various human tissues.Finally,western blot was used to detect relevant protein expression in HT22 cells after semaglutide intervention. RESULTS AND CONCLUSION:With the dataset in DisGeNET database,3 374 differentially expressed genes between Alzheimer's disease patients and healthy people were obtained,and meanwhile,101 target genes of semaglutide potential drugs were obtained.There were 23 intersection genes between them.Ten key genes were identified based on the protein-protein interaction network,which were silent information regulator 1(SIRT1),CASP9,CCND1,CASP1,KEAP1,DLG4,CASP4,GRB2,GRIA1,and EDNRA.The results of GO gene functional annotation analysis of key genes showed that the positive regulatory activity of cysteine endopeptidase,the positive regulation of proteolysis,and the positive regulation of cysteine endopeptidase involved the cytoplasmic part of the apoptotic activity process;AMPA glutamate receptor complex,inflammatory complex,CARD domain binding,cysteine endopeptidase activity,and cysteine endopeptidase activity were involved in the apoptotic process.The results of KEGG signaling pathway analysis indicated that colorectal cancer,non-small cell carcinoma,and endometrial carcinoma were related to immune infiltration,inflammation and autophagic apoptosis.In addition,according to the association ranking of key genes and their distribution in different tissues of HPA online database,SIRT1 was identified as the most significant differential gene.The expression level of SIRT1 protein was significantly down-regulated in HT22 cells after β-amyloid protein 1-42 treatment,but it could be significantly increased after being treated with semaglutide.To conclude,SIRT1 may be a target gene for semaglutide in the treatment of Alzheimer's disease.
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Diabetic retinopathy (DR) is one of the most frequent complications of diabetes (T2DM), which is the main eye disease causing blindness in adults in recent years. At present, glucagon-like peptide-1 receptor agonists (GLP-1RA) have become the main drugs used in the treatment of diabetes due to its superior hypoglycemic, lipid-lowering, hypertensive and cardiovascular effects. A large number of studies have shown that GLP-1RA drugs can protect retinal microvascular and optic nerves in the treatment of diabetes through various ways, but some studies have found that GLP-1RA drugs represented by semaglutide may lead to the progress of DR. Therefore, GLP-1RA should be used cautiously for patients who with severe non-proliferative DR or proliferative DR. Regardless of whether T2DM patients are complicated with DR, the fundus retinal condition should be monitored regularly after the use of GLP-1RA drugs, and timely countermeasures should be taken when DR occurs and develops. The benefits of GLP-1RA used by diabetes patients are obvious to all, and scientific and rational drug use can prevent the occurrence and progress of DR, which can better benefit DR Patients.
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@#With the development of Semaglutide Injection(Ozempic~?)and Rybelsus~?,also known as(Semaglutide Tablets?),the original research drugs have been listed in China,and domestic biopharmaceutical companies are developing an increasing number of Semaglutide biosimilar drugs according to the biosimilar drug pathway. This paper reviews the current status of registration and research and development of original research drugs and biologically similar drugs of Semaglutide both domestically and internationally,analyzes the challenges and related technical requirements in quality research and quality similarity evaluation of Semaglutide,and combines the evaluation practice to analyze and explore common problems in pharmaceutical evaluation of Semaglutide biologically similar drugs,in order to provide reference for the pharmaceutical development and evaluation of such biologically similar drugs.
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Obesity and diabetes, one of the most common diseases can cause a several complications. In diabetic patient with type 2 we mainly use an oral medication with varies mechanism of action such as: GLP-1 medication. To look at semaglutide's (a new glucagon-like peptide receptor agonist; GLP-1 RA) effectiveness in treating individuals with diabetes and obesity. We followed the guidelines of the PRISMA checklist for conducting this study. On 23rd October 2022, we run a systematic search ““semaglutide”, “GLP1”, ''diabetes type 2'', ''obese'' and ''HBA1C''” in five databases named: Scopus, Google Scholar, PubMed, Virtual Health Library and Web of Science. We included 18 papers. Subcutaneous semaglutide was used in ten placebo-controlled and seven active-controlled trials, including nine hundred fifty-five participants. We were only able to locate one oral semaglutide experiment. When compared to a placebo, subcutaneous semaglutide 0.5 and 1 mg reduced HbA1c by 1.01% (95% CI 0.56 to 1.47, I2=93%) and 1.38% (1.05 to 1.70, I2=90%), respectively. The glycemic effectiveness of both dosages was superior to that of other antidiabetic drugs such as insulin glargine, liraglutide, dulaglutide, sitagliptin, and exenatide. Systolic blood pressure, hemoglobin A1c, and body weight are all significantly reduced by semaglutide, a potent once-weekly GLP-1 RA. Nonetheless, there is a higher likelihood of gastrointestinal side effects with it. Results regarding pancreatitis and retinopathy should be evaluated in further post-approval pharmacovigilance studies and interpreted cautiously.
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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)
Subject(s)
Humans , Male , Female , Diabetes Mellitus/epidemiology , Glucagon-Like Peptide-1 Receptor , Obesity/epidemiologyABSTRACT
OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of semaglutide in the treatment of type 2 diabetes mellitus （T2DM）， and to provide reference for clinical drug use. METHODS Rapid health technology assessment was adopted. Retrieved from PubMed， Embase， Cochrane Library， Web of Science， CNKI， Wanfang database， CBM， domestic and foreign HTA official websites， HTA reports， systematic evaluation/meta-analysis and pharmacoeconomic studies about semaglutide in the treatment of T2DM were collected during the inception to May 1st， 2022. After data extraction and quality evaluation， descriptive analysis was performed on the results of included studies. RESULTS A total of 22 pieces of literature were included， involving 7 meta-analyses and 15 pharmacoeconomic studies. In terms of efficacy and safety， semaglutide showed significant advantages in controlling glycated hemoglobin （HbA1c）， fasting blood glucose， postprandial mean glucose， body mass index and achieving a target of glycosylated hemoglobin level ＜7%； also， there was no increased risk of hypoglycaemia or the incidence of serious adverse effects， but the risk of gastrointestinal adverse effects was significantly higher than other interventions. In terms of cost-effectiveness， results of foreign studies showed that semaglutide was more cost-effective， compared with other glucagon-like peptide-1 receptor agonists， sodium-glucose transporter protein 2 inhibitors， dipeptidyl peptidase-4 inhibitors. Research based on the perspective of China’s health system showed that semaglutide had a clear cost-effectiveness advantage over dulaglutide when using GDP per capita in 2020 （72477 yuan） as the payment threshold. CONCLUSIONS The semaglutide has excellent efficacy and good safety for the treatment of T2DM， with cost-effectiveness advantages over a number of drugs， but attention should be paid to the occurrence of gastrointestinal adverse effects.
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Objective@#To evaluate the real-world use of once-weekly semaglutide among Thai patients with type 2 diabetes (T2DM) in a private hospital setting.@*Methodology@#A retrospective review of Thai patients with T2DM who have initiated semaglutide for at least 1 month between June 2020 and March 2022 at Theptarin Hospital, Bangkok, Thailand.@*Results@#A total of 58 patients (50% female, mean age 55.6 ± 15.9 years, with duration of diabetes 12.6 ± 10.3 years, BMI 31.5 ± 4.4 kg/m2, baseline HbA1c 7.9 ± 1.9%, with prior GLP-1 RA use 24.1%, and concomitant SGLT2i intake (41.4%) were included. During a median follow-up of 6 months, the mean serum HbA1c level reduction was 1.3 ± 1.7% with weight loss of 4.7 ± 4.1 kg. The proportion of patients who achieved optimal and sustainable glycemic control (HbA1c <7.0%) increased from 43.1% to 55.8% at the last follow-up. The proportion of patients reaching both HbA1c targets of <7.0% and 5% weight loss was 27.8%. No cases of pancreatitis, cancer, or progressive retinopathy were observed.@*Conclusion@#In this single center undertaking, it was shown that in among persons with T2DM and obesity in Thailand, semaglutide was associated with short-term glycemic control and weight loss comparable with what has been observed in randomized clinical trials and other RWE.
Subject(s)
Asian PeopleABSTRACT
@#Abstract： Objective To develop and validate a reverse phase⁃high performance liquid chromatography（RP⁃HPLC） method for determination of residual N⁃hydroxy succinimide（NHS）content in semaglutide. Methods A RP⁃HPLC method was developed based on the screening of chromatographic column and optimization of mobile phase（phosphate concentration and the ratio of acetonitrile），validated for specificity，suitability，accuracy，reproducibility and stability， and determined for linear range，limit of quantitation（LOQ）and limit of detection（LOD）. The NHS contents in three batches of semaglutide were determined by the developed method. Results The optimal condition for RP⁃HPLC was as follows：CAPCELL PAK ADME column（4. 6 mm × 150 mm，3 μm）was adopted，serving 0. 05 mol／L potassium dihy⁃ drogen phosphate solution⁃acetonitrile（98∶2）as mobile phase A，and 70% acetonitrile as mobile phase B with gradient elution（0 min，0% B；10 min，0% B；19 min，90% B；19. 1 min，0% B；25 min，0% B）at a flow rate of 0. 8 mL／min. The detection wave length was set at 260 nm，while the column temperature was 30 ℃. The developed method showed good specificity and systemic suitability，of which the linear range was 0. 2 ~ 3. 0 μg／mL（R2 = 1. 000 0），while the LOD and LOQ were 4. 8 and 9. 6 ng respectively. The RSD of recovery rates of NHS samples at three concentrations was 0. 58%， indicating a high accuracy. The RSD of NHS contents in six test samples was 0. 16%，indicating a high reproducibility. The RSD of peak areas of NHS after storage at room temperature for 0，4，8，12，16，20 and 24 h was 0. 34%，indicating a high stability. No NHS was detected in three batches of semaglutide by the developed method. Conclusion The developed RP⁃HPLC method is simple and sensitive，which may be used for the determination of NHS content in semaglutide.
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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.
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ABSTRACT Pulmonary aspiration of gastric residues during anesthesia is a potentially fatal complication for which no specific treatment is available. The primary way to prevent its occurrence in the context of elective surgeries is adherence to fasting protocols. However, some clinical conditions can prolong the gastric emptying time, and the risk of aspiration may exist despite adequate fasting. Recognizing the risk factors for gastroparesis allows the adoption of preventive methods and is the primary way to reduce morbidity and mortality from pulmonary aspiration. In this scenario, the anesthesiologist can investigate the gastric content by using ultrasound, adjust the anesthetic technique, and even postpone elective surgeries. Here, we describe incidental computed tomography finding of solid contents in the stomach of a patient without prior identification of the risk factors for gastroparesis. The patient underwent elective renal nodule ablation under general anesthesia after fasting for 9 hours. During the procedure, solid contents in the stomach were noted on computed tomography. Subsequently, it was discovered that the patient had been using semaglutide for 6 days and had not disclosed this information. Semaglutide use may represent a new and significant risk factor for anesthesia-related pulmonary aspiration. Until studies provide information on the appropriate perioperative management of patients using semaglutide, anesthesiologists need to adopt preventive measures to avoid aspiration. Awareness of this potential association and open communication among patients, physicians, and anesthesia teams are essential for enhancing patient safety.
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The glucagon-like peptide-1 receptor agonists (GLP-1RAs) have important beneficial effects on glycemic control and body weight along with their pleiotropic effects on various systems of the body. However, until now these agents were administered via an injection posing a challenge to patient convenience. Oral semaglutide is a first in class oral GLP-1RA co-formulated with an absorption enhancer for the treatment of type 2 diabetes mellitus (T2DM). The clinical efficacy and safety of oral semaglutide has been extensively evaluated in the Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) program of clinical trials. This review shall elaborate on the unique diabetes situation in India and why the oral GLP-1RA (semaglutide) will be a game-changer in the Indian setting
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Oral semaglutide is the newest discovery, the first in class peptide in a pill. Sodium N-(8-[2-hydroxybenzoyl]amino)caprylate (SNAC), a small fatty acid, has been co-formulated with semaglutide, which facilitates its absorption from the gastric mucosa. It has 94% homology with human glucagon-like peptide 1 (GLP-1). It comes in three dose forms – 3 mg, 7 mg and 14 mg. It is given as once daily dosing and is recommended in adult type 2 diabetes mellitus patients as monotherapy when metformin is contraindicated or not tolerated and in combination with other oral antidiabetic drugs (OADs). In a phase 3 trial, it has been shown to reduce glycated hemoglobin (HbA1c) up to 1.5%, with weight reduction up to 5 kg with a 14 mg dose. There was nonsignificant risk reduction of 21% in 3-point major adverse cardiovascular events (MACE) and 51% and 49% risk reduction in cardiovascular (CV) deaths and all-cause mortality, respectively. Oral semaglutide was found to be superior to empagliflozin, sitagliptin and liraglutide in both glycemic control and weight reduction. It also exhibits many pleiotropic effects – reduced energy intake, anti-inflammatory and anti-atherosclerotic effect, to name a few. Nausea was the most common side effect which was experienced by only 15% to 20% of patients. It was mild-to-moderate and transient. Overall, oral semaglutide has shown its efficacy both early and late in the management of diabetes, irrespective of renal and hepatic impairment.
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Obesity is an important risk factor of type 2 diabetes (T2D), which has become an important factor threatening human health. However, no perfect drug choice for obesity exists. Semaglutide is a kind of human glucagon-like peptide-1 (GLP-1) analog that promotes insulin secretion while inhibiting glucagon secretion through a glucose concentration-dependent mechanism. GLP-1 can also delay stomach emptying and suppress appetite to help lose weight. This review summarizes clinical evidence of the semaglutide effect on T2D and obesity and establishes expectations on future clinical trials for obesity treatment.
Subject(s)
Humans , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/therapeutic use , Glucagon-Like Peptides , Hypoglycemic Agents/therapeutic use , Motivation , Obesity/drug therapyABSTRACT
OBJECTIVE To exc avate the adverse drug event （ADE）signals of semaglutide and provide reference for its clinical rational use. METHODS The proportional unbalance method was used to mine the signals of all semaglutide ADE reports from FDA Adverse Event Reporting System （FAERS）up to September 2021. The basic situations of the reported cases were analyzed. The corresponding system organ classification （SOC）was mapped and compared with the adverse drug reactions recorded in the drug instructions. Preferred terms （PT）of patients with different indications were analyzed. RESULTS A total of 6 661 semaglutide ADE reports were extracted and 194 valid signals were mined. Among 6 661 cases of ADE ，the proportion of men （43.40％）was lower than women （52.65％）；the age was mainly distributed in ＞40-65 years old （29.00％）and ＞65 years old （22.61％）；the reporting country was mainly the United States （83.88％）；the report year was mainly concentrated in 2021 （40.88％），with an increasing trend year by year ；the main outcome was hospitalization or prolonged hospitalization in serious ADE reports （17.78％）. Semaglutide ADE signal was mapped to the main SOC ，mainly including gastrointestinal diseases ，various injuries，poisoning and operation complications ，metabolic and nutritional diseases ，various examinations. The screening criteria were based on the report odds ratio ＞10 or ADE reported cases ＞50，and 48 new potential adverse drug reactions were added to the drug description. Among the indications with the top two reported cases （type 2 diabetes and obesity ，overweight，weight control），the frequency of gastrointestinal system related ADE reports represented by nausea ，vomiting and diarrhea was higher ， which was similar to the drug instructions. CONCLUSIONS This study supplemented 48 new potential adverse drug reactions based on the drug instructions of semaglutide. At present ，it can be considered that semaglutide is safe.
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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.
Subject(s)
Obesity , Weight LossABSTRACT
OBJECTIVE：To systematically evaluate th e efficacy and safety of glucagon-like peptide 1 receptor agonists semaglutide in the treatment of type 2 diabetes mellitus （T2DM），and to provide evidence-based reference for clinical treatment of T2DM. METHODS ：Retrieved from PubMed ，Embase，the Cochrane library ，ClinicalTrials.gov，CBM，CNKI and VIP ， randomized controlled trials （RCT） about oral semaglutide 3 mg，7 mg and 14 mg （trial group ） versus placebo or other glucose-lowering drugs （control group ）in the treatment of T 2DM were selected during the inception to May 2020. After extracting data from clinical studies that met the inclusion criteria ，quality evaluation was carried out with Cochrane systematic evaluation manual 5.1.0，Meta-analysis was performed by using Rev Man 5.3 statistical software. RESULTS ：A total of 6 RCTs involving 5 334 patients were included. Results of Meta-analysis showed that compared with control group ，trial group could significantly decreased HbA 1c level { 26 weeks [MD＝－0.62，95％CI（－0.88，－0.36），P＜0.001]，52 weeks [MD＝－0.51，95％CI（－0.72， －0.29），P＜0.001]}，FPG level { 26 weeks [MD＝－0.89，95％ CI（－1.31，－0.48），P＜0.001]，52 weeks [MD＝－0.68，95％CI （－1.05，－0.31），P＜0.001]}；significantly increased the compliance rate of HbA 1c＜7％ {26 weeks [RR＝2.22，95％CI（1.68， 2.93），P＜0.001]，52 weeks [RR＝2.02，95％CI（1.51，2.70），P＜0.001]}；significantly decreased the self-measured plasma glucose ， body weight and diastolic blood pressure （DBP）after 26 and 52 weeks of treatment，self-measured postprandial glucose cstc2015zdcy-ztzx120005） after 26 weeks of treatment and systolic blood pressure （SBP） E-mail： after 52 weeks of treatment（P＜0.05）. Subgroup analysis of different doses showed that compared with control group ，3 mg subgroup could significantly decreased the body weight after 26 and 52 weeks of treatment and DBP a fter 52 weeks of treatment ；7 mg subgroup could significantly decreased the HbA 1c levels and body weight after 26 and 52 weeks of treatment ，the FPG levels and the self-measured plasma glucose after 26 weeks of treatment and the SBP after 52 weeks of treatment ，increased the compliance rate of HbA 1c＜7％ after 26 weeks of treatment. The 14 mg subgroup could significantly decreased the HbA 1c levels ，the FPG levels ，the self-measured plasma glucose levels ，the body weight and the SBP after 26 and 52 weeks of treatment ，and self-measured postprandial glucose after 26 weeks of treatment ，while increased the complication rate of HbA 1c＜7％ after 26 and 52 weeks of treatment （P＜0.05）. The incidence of hypoglycemia events in trial group [RR ＝0.84，95％CI（0.72，0.97），P＝0.02] was significantly lower than control group ，but the incidence of adverse events [RR ＝1.23，95％CI（1.09，1.40），P＝0.001] and gastrointestinal reaction [RR ＝1.99，95％CI（1.55，2.57），P＜0.001] were significantly higher than control group. There was no significant difference in the incidence of serious adverse events or infection between 2 groups（P＞0.05）. CONCLUSIONS ：Oral semaglutide can effectively decrease blood glucose level ，increase the compliance rate of HbA 1c＜7.0％，reduce the body weight and blood pressure level of T 2DM patients ，and the 14 mg subgroup has the best effect. When using somaluptide ， we should pay attention to the occurrence of adverse events ， especially gastrointestinal adverse events.
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OBJECTIVE： To systematically evaluate therapeutic efficacy and safety of long-acting glucagon like peptide-1 （GLP-1） receptor agonist Semaglutide vs. placebo or other glucose-lowering drugs in the treatment of type 2 diabetes mellitus （T2DM）， and to provide evidence-based reference for T2DM in clinic. METHODS： Retrieved from PubMed， Embase， Medline， Cochrane library， randomized controlled trials （RCT） about Semaglutide （trial group） vs. placebo or other glucose-lowering drugs （control group） in the treatment of T2DM were selected during the establishment of database to Sept. 2018. After data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0， Meta-analysis was performed for HbA1c level and compliance rate， fasting plasma glucose （FPG） level， systolic blood pressure （SBP）， diastolic blood pressure （DBP）， body mass index （BMI）， body weight pulse frequency level， the incidence of hypoglycemia and gastrointestinal reaction by using Rev Man 5.3 software. RESULTS： A total of 12 RCTs involving 9 966 patients were included. The results of Meta-analysis showed that compared with control group， trial group could effectively decrease the levels of HbA1c [MD＝－1.03， 95％CI（－1.22，－0.85）， P＜0.001] and FPG [MD＝－1.14， 95％CI（－1.53，－0.76）， P＜0.001]， increase compliance rate of HbA1c [RD＝0.40， 95％CI（0.31，0.49）， P＜0.001]， reduce SBP [MD＝－2.61， 95％CI （－3.23， －1.98）， P＜0.001] and DBP [MD＝－0.56， 95％CI （－0.96， －0.16）， P＝0.006]， decrease BMI [MD＝－1.25， 95％CI （－1.51， －0.99）， P＜0.001] and body weight [MD＝ －3.60， 95％CI（－4.24， －2.96）， P＜0.001]， increase pulse frequency [MD＝2.16， 95％CI （1.51， 2.81）， P＜0.001]. The major adverse drug reactions were gastrointestinal reaction； the incidence of gastrointestinal reaction was higher than control group [RD＝0.20， 95％CI（0.15，0.26）， P＜0.001]， but there was no statistical significance in the incidence of hypoglycemia events between 2 groups [RD＝0.00， 95％CI（－0.01，0.02）， P＝0.44]. CONCLUSIONS： Semaglutide can significantly decrease HbA1c， FPG， body weight， blood pressure and increase pulse frequency in T2DM patients， and increase the compliance rate of HbA1c. Although the incidence of gastrointestinal reaction is higher than control group， but the risk of hypoglycemia is not higher， indicating Semaglutide is well tolerated and safe.
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OBJECTIVE:To evaluate the efficacy and safety of semaglutide in the treatment of type 2 diabetes mellitus,and to provide evidence-based reference in clinic. METHODS:Retrieved from Wangfang,CNKI,PubMed,Embase,Medline and the Cochrane library,randomized controlled trials(RCTs)about semaglutide alone or combined with other hypoglycemic drugs(trial group)versus placebo or other hypoglycemic medicine alone or combination(control group)in the treatment of type 2 diabetes mellitus were collected. After data extraction and literature quality evaluation,Meta-analysis was performed by using Rev Man 5.3 software. RESULTS:Totally 7 literatures were included,involving 7 708 patients. Results of Meta-analysis showed that compared with control group,the level of glycosylated hemoglobin [vs. placebo:MD＝－1.48,95%CI(－1.68,－1.28),P＜0.001;vs. positive control medicine:MD＝－0.95,95%CI(－1.17,－0.73),P＜0.001],fasting plasma glucose [vs. placebo:MD＝－1.87, 95%CI(－2.25,－1.50),P＜0.001;vs. positive control medicine:MD＝－1.07,95%CI(－1.58,－0.55),P＜0.001],body weight [vs. placebo:MD＝－3.15,95%CI(－3.98,－2.32),P＜0.001;vs. positive control medicine:MD＝－3.64,95%CI (－4.60,－2.69),P＜0.001] and body weight index [vs. placebo:MD＝－1.11,95%CI(－1.40,－0.81),P＜0.001;vs. positive control medicine:MD＝－1.34,95%CI(－1.67,－1.00),P＜0.001] in trial group were decreased significantly. For safety,the incidence of nausea and diarrhea of somaglutide was significantly higher than control group(P＜0.05). CONCLUSIONS:Semaglutide showes superiority in reducing the levels of glycosylated hemoglobin,fasting plasma glucose,body weight and body weight index in patients with type 2 diabetes mellitus,but the occurrence of nausea and diarrhea in patient should be monitored.