司美格鲁肽治疗2型糖尿病的快速卫生技术评估

目的 采用快速卫生技术评估评价司美格鲁肽治疗2型糖尿病的有效性、安全性和经济性。方法 检索Embase、PubMed、the Cochrane Library、中国知网、万方数据库和卫生技术评估相关的网站。由2名评价者独立地根据纳入、排除标准筛选文献,提取数据,评价文献质量并进行分析。结果 共纳入12篇系统评价/meta分析,13篇药物经济学研究。结果显示,在有效性方面,司美格鲁肽能够显著降低HbA1c、FPG和SBP水平,并减轻体质量;在安全性方面,司美格鲁肽的胃肠道不良反应发生率相对更高,同时司美格鲁肽并不会增加低血糖和急性胰腺炎的发生率;在经济性方面,司美格鲁肽能够延长患者的质量调整生命年,其增量成本效果比低于所在国家的意愿支付阈值,具有成本效果优势。结论司美格鲁肽治疗2型糖尿病具有较好的有效性、安全性和经济性。     

不同胰高糖素样肽-1受体激动剂在中国2型糖尿病患者达到治疗目标的短期成本分析

目的 本研究评价一年的时间内,在中国医疗保健体系内使用不同胰高糖素样肽-1受体激动剂（GLP-1RA）对中国2型糖尿病患者实现HbA1c治疗目标和减重的相对成本。方法 使用SUSTAIN3、SUSTAIN7和SUSTAIN10的研究结果,分析达到血糖控制、不增加体重和低血糖发生结果相关的单终点和复合终点的患者比例。根据患者比例计算达到临床治疗目标所需要的人数、年成本和相对成本。计算成本依据患者使用药物的年度成本,以2022年中国医保定价RMB(CN)表示。结果 司美格鲁肽更有效地使患者达到每个终点和复合终点,达到临床治疗目标所需要的人数（NNT）更少。达到HbA1c <7%目标艾塞那肽缓释剂、度拉糖肽、利拉鲁肽控制成本分别是司美格鲁肽的4.77,1.64,2.53倍;而达到HbA1c <7%无低血糖和体重增加目标分别是司美格鲁肽的6.27,1.74,2.89倍。结论 在中国治疗2型糖尿病患者方面,与艾塞那肽缓释剂、度拉糖肽、利拉鲁肽相比,司美格鲁肽具有更好的性价比。     

基于美国FAERS数据库的司美格鲁肽不良事件信号挖掘

摘要：目的:挖掘司美格鲁肽的不良事件（ADE）信号,为临床合理安全用药提供参考。方法:采用报告比值比（ROR）法和比例报告比值法（PRR）对美国食品药品管理局不良事件报告系统（FAERS）数据库2017年12月～2020年第四季度收录的司美格鲁肽相关报告挖掘ADE信号。从国际医学用语词典（MedDRA）的首选语（PT）、高位语（HLT）、标准MedDRA分析查询（SMQ）等3个方面分析司美格鲁肽ADE信号。结果:以司美格鲁肽为首要怀疑药品的ADE报告数3 839份,PT层级上报频数前50位事件检出36个信号,HLT层级得到64个信号,SMQ层级得到16个信号。安全信号主要表现为胃肠道不良反应、低血糖、糖尿病视网膜病变并发症和急性胰腺炎等。结论:利用挖掘FAERS数据库可较全面深入地分析研究司美格鲁肽上市后的ADE,为临床安全合理用药提供依据。临床应用司美格鲁肽时,应密切关注该药的ADE,尽早采取干预措施,保证患者安全有效用药。     

司美格鲁肽与利拉鲁肽治疗糖尿病合并肥胖症的效果对比

目的：探究司美格鲁肽与利拉鲁肽在治疗糖尿病合并肥胖症患者中的临床价值。方法：选择2021年8月—2023年4月于本院接受治疗的100例糖尿病合并肥胖症患者为研究对象,按照随机数字表法分为观察组和对照组,每组50例。对照组予以利拉鲁肽治疗,观察组予以司美格鲁肽治疗,比较两组糖代谢指标水平、血脂代谢指标水平、氧化应激指标水平、不良反应。结果：治疗12周后,观察组FBG水平、HOMA-IR、低密度脂蛋白水平、总胆固醇水平、BMI指数以及腹围均低于对照组,高密度脂蛋白水平高于对照组（P<0.05）;观察组不良反应总发生率与对照组比较,差异无统计学意义（P>0.05）。结论：司美格鲁肽与利拉鲁肽在改善糖尿病合并肥胖症血糖、血脂及体重指标方面均具有较好的效果,安全性也相当,但司美格鲁肽较利拉鲁肽效果更好。     

司美格鲁肽和度拉糖肽的控制成本分析

目的:采取中国卫生体系视角，计算40周治疗期间司美格鲁肽和度拉糖肽达到治疗目标的控制成本。方法:达到与血糖控制、体质量、低血糖结局相关的单一和复合终点的患者比例(数据)来自SUSTAIN7研究。成本测算包括药品费用、针头和不良反应成本。控制成本的计算方法是将每位患者使用每种药物的总成本，以2 022元人民币(CNY)表示，除以达到每个临床治疗终点的患者比例。结果:每周一次皮下注射0.5 mg司美格鲁肽(0.5 mg/周司美格鲁肽)在使患者达到治疗目标上更有效，且在各临床终点下显示出更低的控制成本。对于每名患者达到三联复合终点的成本，0.5 mg/周司美格鲁肽为7 321.3元，1.5 mg/周度拉糖肽为10 477.4元，1.5 mg/周度拉糖肽较司美格鲁肽高出43.1%。对于HbA1c≤6.5%、HbA1c<7%、HbA1c降低≥1.0%且体质量减轻≥3.0%、体质量减轻≥5%、体质量减轻≥10%而言，使用1.5 mg/周度拉糖肽相较使用0.5 mg/周司美格鲁肽的成本分别增加35.2%、31.6%、96.4%、90.2%和127.0%。结论:对于中国2型糖尿病患者的治疗而言，...     

GLP-1类似物——司美格鲁肽研究进展

司美格鲁肽是诺和诺德公司自主研发的新型长效GLP-1类似物,2021年4月已成功获批在我国上市,司美格鲁肽作为一种新型长效GLP-1类似物以利用突破性技术将其半衰期延长至7 d,每周一次的用药方式大大提高了患者的用药依从性,本文就司美格鲁肽研究进展进行综述.     

司美格鲁肽调节小鼠糖脂代谢的转录组学分析

目的 探究司美格鲁肽对糖脂代谢的调控作用。方法 测定db/db小鼠的体重、血糖、血脂、葡萄糖耐量、胰岛素耐量以及组织病理学,考察司美格鲁肽对糖脂代谢的改善作用;对小鼠的肝脏组织进行mRNA测序及结果分析。结果 司美格鲁肽可显著改善小鼠的空腹血糖、葡萄糖耐量、胰岛素耐量、甘油三酯、肝脏脂肪变性、糖原沉积及脂滴沉积。转录组学分析显示：司美格鲁肽回调的差异基因有282个,涉及多条糖脂代谢通路;参与糖脂代谢的共有基因Acaca及Fasn均在给药后下调。结论 司美格鲁肽能调节核苷磷酸盐代谢过程、脂肪酸生物合成和代谢过程、AMPK信号通路、胰岛素信号通路等多条涉及糖脂代谢的途径,可能是通过下调Acaca及Fasn基因来改善糖脂代谢紊乱。     

胰高血糖素样肽1受体激动剂周制剂的Mini卫生技术评估

目的 对我国上市的4种胰高血糖素样肽1受体激动剂（GLP-1RA）周制剂进行综合评估，为医院优化药品目录和临床合理用药提供依据。方法 采用Mini卫生技术评估法，参照《中国医疗机构药品评价与遴选快速指南》建立评价细则，从药学特性、有效性、安全性、经济性、其他属性5个维度对4种GLP-1RA周制剂进行综合评价。结果 4种GLP-1RA周制剂的Mini卫生技术评分从高至低依次为度拉糖肽78.60分、司美格鲁肽77.35分、聚乙二醇洛塞那肽67.40分、艾塞那肽微球65.50分。其中，度拉糖肽在降糖获益、动脉粥样硬化性心血管疾病获益、肾病获益、经济性方面有优势；司美格鲁肽在降糖减重方面有优势，但经济性低于度拉糖肽；艾塞那肽微球在儿童人群中使用有优势，但日均治疗费用最高；聚乙二醇洛塞那肽需要进一步的临床证据。结论 4种GLP-1RA周制剂总体均具有较高的综合分值，其中度拉糖肽和司美格鲁肽可能具有更全面的药学价值，而艾塞那肽微球针对儿童人群具有唯一性。     

基于OpenFDA数据挖掘和分析司美格鲁肽的不良事件报告信号

目的:对司美格鲁肽安全警戒信号进行挖掘与分析,为临床安全用药提供参考.方法:检索并提取美国食品药品管理局(FDA)不良事件报告系统(FAERS)2017年12月1日～2021年9月30日司美格鲁肽相关的药品不良事件(ADE)报告,并对相关数据进行分析.结果:提取得到的5185800份ADE报告中,以司美格鲁肽为怀疑药物...     

3种胰高糖素样肽-1受体激动剂周制剂遴选评价：基于医院卫生技术评估

目的 对司美格鲁肽、度拉糖肽和洛塞那肽3种胰高糖素样肽-1受体激动剂（GLP-1RA）周制剂进行医院卫生技术评估（HB-HTA），探索HB-HTA在医院药物遴选中的应用模式与前景，为医院基本用药供应目录科学调整提供循证依据。方法利用药品HB-HTA快速评分体系，从临床治疗必需性、有效性、安全性、经济性、依从性、国家基本药物属性、医保属性、质量层次、包装属性、药品企业属性、市场属性等11个维度分别对司美格鲁肽、度拉糖肽和洛塞那肽进行评价。结果 司美格鲁肽、度拉糖肽和洛塞那肽总得分分别为65,64,60，均可安全有效地控制血糖并增加心血管获益，且一周使用一次的优势可提高患者依从性、改善生活质量。但上述3种药品在包装属性、市场属性等方面具有一定差异，可根据实际需求遴选药品。结论 本次HB-HTA可为医院遴选与合理使用3种GLP-1RA周制剂提供循证依据，为建立基于HB-HTA的药品管理决策支持体系提供思路。     

Sgemaglutide in type 2 diabetes – is it the best glucagon-like peptide 1 receptor agonist (GLP-1R agonist)?

Introduction: Glucagon-like peptide-1 (GLP-1) is produced by the gut, and in a glucose-dependent manner stimulates insulin secretion while inhibiting glucagon secretion, reduces appetite and energy intake, and delays gastric emptying. The GLP-1R agonist semaglutide has recently been registered to treat type 2 diabetes.

Area covered: This review is of semaglutide in type 2 diabetes, and considers which properties of this GLP-1R agonist, may be responsible for its clinical outcome benefits .

Expert opinion: The pharmacokinetics of semaglutide make it ideal for once-weekly dosing. SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) showed that semaglutide 0.5 or 1 mg subcutaneously once-weekly reduced cardiovascular outcomes in subjects with type 2 diabetes and cardiovascular disease or risk, mean age 65 years, baseline HbA1c 8.7% and mean body weight of 92 kg. Although, semaglutide may be a useful drug in this population, it increased retinopathy to a small extent and this needs further investigation. Also, it is not known whether semaglutide will improve cardiovascular outcomes in other populations including those with lower ages, HbA1c values, and body weights similar to those included in the unsuccessful clinical outcome trials with the GLP-1R agonists, lixisenatide and exenatide.     

司美格鲁肽治疗肥胖的研究进展

全球范围内,肥胖已经成为一个严重的公共健康危机,且发病率不断增高。肥胖和一系列并发疾病给医疗保健系统带来了巨大负担,如何更有效减轻体质量已经成为当今社会的一个热点,仅靠单纯的生活干预很难控制,因此作为辅助手段的抗肥胖药物受到广泛的关注,但目前被批准用于减轻体资料的药物相对较少。司美格鲁肽是一种新型的胰高血糖素样肽-1受...     

A randomized study investigating the effect of omeprazole on the pharmacokinetics of oral semaglutide

Background: Since the first oral glucagon-like peptide-1 analog comprises semaglutide co-formulated with an absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, which induces a transient, localized increase in gastric pH, we have investigated whether a proton pump inhibitor affects the pharmacokinetics of oral semaglutide.

Research design and methods: A single-center, randomized, open-label, parallel-group trial investigated pharmacokinetic interactions of oral semaglutide with omeprazole (40 mg once-daily) in 54 healthy subjects. Primary endpoints were area under the plasma concentration-time curve over 24 h for semaglutide (AUC_{0?24h,semaglutide,Day10}) and maximum concentration of semaglutide (C_{max,semaglutide,Day10}) at day 10.

Results: Exposure of semaglutide appeared to be slightly increased, although not statistically significantly, with oral semaglutide plus omeprazole versus oral semaglutide alone (AUC_{0?24h,semaglutide,Day10} [estimated treatment ratio 1.13; 90%CI 0.88, 1.45] and C_{max,semaglutide,Day10} [estimated treatment ratio 1.16; 90%CI 0.90, 1.49]). Gastric pH was higher with oral semaglutide and omeprazole versus oral semaglutide alone. Adverse events were mild or moderate and, most commonly, gastrointestinal disorders.

Conclusions: There was a slight non-statistically significant increase in semaglutide exposure when oral semaglutide was administered with omeprazole, but this is not considered clinically relevant and no dose adjustment is likely to be required.     

Quantifying the Value of Orally Delivered Biologic Therapies: A Cost-Effectiveness Analysis of Oral Semaglutide

Oral semaglutide, which has undergone multiple phase 3 clinical trials, represents the first oral biologic medication for type 2 diabetes in the form of a daily capsule. It provides similar efficacy compared with its weekly injection counterpart, but it demands a dose on the order of 100 times as high and requires more frequent administration. We perform a cost effectiveness analysis using a first and second order Monte Carlo simulation to estimate quality-adjusted life expectancies associated with an oral daily capsule, oral weekly capsule, daily injection, and weekly injection of semaglutide. We conclude that the additional costs incurred to produce extra semaglutide for the oral formulation are cost effective, given the greater quality of life experienced when taking a capsule over a weekly injection. We also demonstrate that the potency of semaglutide allows the formulation to be cost effective, and less potent drugs will require increased oral bioavailability to make a cost effective oral formulation.     

A Review on the Efficacy and Safety of Oral Semaglutide

There are numerous treatment options currently available for patients with type 2 diabetes mellitus; however, a multitude of patients continue to have inadequately controlled glycemic levels with their current antihyperglycemic regimen. Furthermore, the American Diabetes Association guidelines increasingly highlight the importance of multifactorial management and optimizing medication regimens that include cardiovascular, renal, and/or weight benefits in patients with type 2 diabetes mellitus. Glucagon-like peptide-1 receptor agonists belong to a novel class of type 2 diabetes mellitus agents that are becoming increasingly prevalent owing to their ability to improve glycemic status without the risk of hypoglycemia. Currently, there are three US Food and Drug Administration-approved glucagon-like peptide-1 receptor agonists, subcutaneous semaglutide, dulaglutide, and liraglutide, that also have an indication for reducing major adverse cardiovascular events in patients with type 2 diabetes mellitus and established cardiovascular disease. However, these agents are not often the first options because of their subcutaneous administration. Nevertheless, co-formulation of oral semaglutide with an absorption enhancer has shown to increase its bioavailability and has made its oral absorption possible. In the PIONEER trials, oral semaglutide effectively lowered blood glucose levels, and showed benefits on weight and cardiovascular outcomes; however, there is no Food and Drug Administration indication approved yet as the SOUL trial is still ongoing. Such characteristics of oral semaglutide may improve and increase its use compared to subcutaneous agents and possibly lead to earlier cardiovascular protection in addition to achieving glycemic control.     

Efficacy and safety of once-weekly semaglutide for the treatment of type 2 diabetes

Introduction: Type 2 diabetes is a chronic metabolic disease characterized by persistent hyperglycemia resulting from progressive deficient of insulin in patients with a background of insulin resistance. Current treatment algorithms recommended by American Diabetes Association/The European Association for the Study of Diabetes promote a patient-centered approach that takes into account a comprehensive consideration of pharmacological properties of drugs, including glucose-lowering action, effects on body weight, correction on multiple pathophysiologic defects, tolerability, and long-term safety. Glucagon-likepeptide1 (GLP-1) receptor analogues are appealing due to the improved glycemic control in a glucose-dependent manner, modest weight loss and low risk of hypoglycemia.

Areas covered: Semaglutide (Novo Nordisk), a once-weekly GLP-1 analogue, is currently in the phase III clinical trial for the treatment of type 2 diabetes. This article aims to review the pharmacological and clinical profiles of semaglutide based on the available clinical data.

Expert opinion: Semaglutide achieved greater reduction from baseline in HbA_1c in comparison to placebo. The greater proportion of patients in semaglutide group than that in placebo group achieved target HbA_1c <7.0% and <6.5%, respectively. Semaglutide is the second GLP-1 analogue contributing to the reduced bodyweight and improving obesity related complications. More importantly, semaglutide is beneficial to diabetic patients with high cardiovascular risk according to the recently completed phase III trial. The incidence of gastrointestinal adverse effects increased with semaglutide dose.     

Comparative efficacy of once-weekly semaglutide and SGLT-2 inhibitors in type 2 diabetic patients inadequately controlled with metformin monotherapy: a systematic literature review and network meta-analysis

Objective: Treatment intensification with additional anti-diabetic agents is recommended in type 2 diabetes (T2D) for patients inadequately controlled on metformin monotherapy. The present network meta-analysis (NMA) evaluated comparative efficacy and safety of once-weekly semaglutide and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) in T2D patients inadequately controlled with metformin.

Methods: Randomized controlled trials with ≥20 weeks duration were searched in EMBASE, MEDLINE, and CENTRAL. Primary efficacy outcomes were: change from baseline in HbA_1c, weight, systolic blood pressure (SBP), post-prandial blood glucose (PPG), and fasting blood glucose (FPG). Treatment effects at 26 (±4) weeks were compared using Bayesian NMAs. Meta-regression and sensitivity analysis were used to address the trial heterogeneity.

Results: Eight trials were found eligible for this NMA. Statistically significant reductions in HbA1c were observed with both 1.0?mg and 0.5?mg doses of once-weekly semaglutide when compared to SGLT-2is. The mean differences in change from baseline in HbA_1c for once-weekly semaglutide 1.0?mg vs SGLT-2is ranged from ?0.66% for canagliflozin 300?mg (95% Credible Intervals [CrI]: ?0.82, ?0.50%) to ?1.11% for dapagliflozin 5?mg (95% CrI: ?1.37, ?0.85%). Once-weekly semaglutide 1.0?mg performed significantly better than all SGLT-2is of interest in reducing weight and improving FPG levels: however, SBP reduction was not statistically differentiable. Results of sensitivity analysis and meta-regressions aligned with base-case results. NMAs were not possible for PPG and safety outcomes, due to lack of data.

Conclusion: Once-weekly semaglutide treatment is significantly better compared to SGLT-2is in achieving adequate glycemic control in T2D patients inadequately controlled with metformin monotherapy.     

已上市胰高血糖素样肽-1受体激动剂的研究进展

胰高血糖素样肽-1受体激动剂（GLP-1RAs）治疗2型糖尿病受到广泛关注,其不仅具有优异的降糖优势,还有控制体质量,调节血脂,改善胰岛β细胞功能等特点,同时低血糖或体质量增加的不良反应发生率较低。自2005年至今,已经有7个GLP-1RAs经美国食品药品监督管理局批准上市,即艾塞那肽、利拉鲁肽、艾塞那肽长效制剂、阿必鲁肽、度拉糖肽、利西拉来和索马鲁肽;在中国上市的有贝那鲁肽和洛塞那肽。对已经上市的9个GLP-1Ras治疗2型糖尿病的临床研究进展进行综述。     

索马鲁肽对早期2型糖尿病心肌病大鼠mTOR信号通路的干预作用

目的 探讨索马鲁肽对糖尿病心肌病大鼠心肌组织哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin,mTOR）信号通路表达的干预作用。方法 高脂饮食5周后,腹腔注射链脲佐菌素建立2型糖尿病大鼠模型,实验将大鼠分为正常对照组、糖尿病2周、4周模型组和索马鲁肽组,索马鲁肽组在造模成功后给予索马鲁肽灌胃处理。4周后,各组动物进行血清学检测,包括空腹血糖、总胆固醇、甘油三酯、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）、空腹胰岛素,超声心动图检测心功能相关指标,Western blot检测心肌mTOR、p-mTOR、S6K1、Atg5和P62蛋白表达变化。结果 与正常对照组比较,2型糖尿病大鼠2周和4周模型血清中总胆固醇、甘油三酯、LDL-C水平显著升高,HDL-C水平显著降低;索马鲁肽组空腹血糖值趋于正常,HDL-C水平升高显著（P<0.05）,LDL-C水平显著降低（P<0.01）。相对于正常对照组,糖尿病模型组大鼠心肌组织中mTOR、p-mTOR、S6K1的表达与正常对照组相比随时间持续增加（P<0.01）,自噬相关蛋白Atg5和P62表达也显著增加（P<0.05）,而索马鲁肽组均显示出降低趋势。结论 在早期糖尿病心肌病的发生发展过程中,索马鲁肽对mTOR信号通路具有抑制作用,能降低心肌细胞自噬损伤的发生。