GLP-1RA治疗减重术后体质量反弹或减重不足患者有效性的系统评价

目的 评价胰高血糖素样肽-1受体激动剂(GLP-1RA)用于治疗术后体质量反弹(WR)或减重不足(IWL)患者的效果。方法 使用计算检索Cochrane Library、Embase、Pubmed、中国知网、万方数据库中关于GLP-1RA治疗减重术后WR或IWL的文献,截止日期2022年10月。采用Cochrane偏倚风险评估工具独立评估RCTs的偏倚风险,使用Newcastle-Attawa Scale(NOS)评估观察性研究。每项研究都由2位评审员独立评估。必要时,通过求助于第3位评审员来解决分歧。采用SPSS 23.0对符合纳入与排除标准的文献进行分析。结果 最终纳入9篇文献,其中6篇为回顾性队列研究,2篇为前瞻性队列研究,1篇为随机对照研究。共有631例患者接受了减重术后GLP-1RA治疗,涉及的GLP-1RA为利拉鲁肽与司美格鲁肽,研究时间为2011年至2022年。每项研究均报告了不同时间节点患者的体质量减轻情况。结论 GLP-1RA治疗对减重术后WR或IWL患者的体质量减轻和改善并发症方面有效果,可以用于减重手术后效果不满意的患者。     

胰高血糖素样肽-1受体激动剂治疗肥胖的研究进展

肥胖对公共健康的威胁日益严重,使患者生活质量降低,死亡风险增加。药物治疗可以帮助肥胖患者减轻体重,且有助于降低体重反弹的风险,从而减少肥胖相关并发症。胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)受体激动剂(glucagon-like peptide-1 receptor agonists,GLP-1RAs)促进胰岛素分泌,并以葡萄糖依赖的方式减少了胰高血糖素的分泌,使胃排空延迟、肠道运动性降低,并且可以激活下丘脑的神经通路和食欲调节区域,使食欲下降、食物摄入减少,从而治疗肥胖。本研究通过对GLP-1RAs治疗肥胖的机制、临床试验、安全性和耐受性、主要不良反应、禁忌证及优势等进行综述,旨在为肥胖的治疗提供理论依据。     

纤维胆道镜临床应用138例分析

目的：探讨及总结纤维胆道镜诊治胆道疾病与非胆道疾病的疗效及诊治经验。方法：回顾性分析1993－1999年临床应用纤维胆道镜的诊治与治疗情况。结果：临床应用138例纤维胆道镜，胆道疾病术中应用83例，75例协助手术一次取净结石，6例肝内Ⅱ～Ⅲ级胆管残留少量结石，留待术中取石。其中12例胆囊切除术经胆囊管检查，发现2例总胆管结石，胆管切开取石治愈。2例总胆管下端梗阻确诊为肿瘤。术后48例中，14例发现肝内外胆管结石，11例一次取净，3例分3次取净。纤维胆道镜应用非胆道疾病22例，均一次使用确诊、治愈。结论：纤维胆道镜不仅可用于胆道疾病围手术期的检查与治疗。亦可用于处理非胆道疾病疑难问题。     

经内镜逆行胰胆管造影联合反向导丝引导治疗胆管疾病

目的 介绍反向导丝与ERCP对接治疗胆道疾病的方法 ,并评价该方法 对胆道疾病治疗的疗效.方法 45例经ERCP失败或不能耐受长时间常规ERCP而采用会师技术治疗的胆道疾病患者,经T管窦道、胆囊造瘘口或者PTCD,将导丝经胆总管导入十二指肠,再经十二指肠镜的活检孔道导出,导管在体外与ERCP导管对接后行胆道痰病的治疗.结果 45例有44例获得成功,经T管窦道30例,胆囊造瘘口2例,PTCD 13例.无严重并发症发生.结论 ERCP失败时,会师技术是治疗胆道疾病的较好方法 ,简便易学,值得临床推广应用.     

胰高血糖素样肽1在糖尿病治疗中的相关研究及应用

正胰高血糖素样肽1(glucagon-like peptide-1,GLP-1)是肠道L细胞分泌的一种肽类激素,它来源于胰高血糖素原前体,是机体在响应营养摄入时释放的一类高效的肠促胰素。GLP-1是近年来2型糖尿病治疗领域研究的热点。GLP-1受体激动剂(GLP-1 receptor agonists,GLP-1RAs)及GLP-1类似物,由于其作用靶点独特、有效性及安全性俱佳而成为降     

术中胆道镜在胆道疾病诊断和术式选择中的价值

目的 :探讨手术中使用纤维胆道镜对胆道疾病的诊断和术式选择的应用价值。方法 :对 15 4例使用术中胆道镜诊断和治疗胆道疾病的临床资料进行分析和总结。结果 :10 8例肝胆管结石患者使用术中胆道镜后胆道结石残留率仅为 10 1% ;7例左肝管、4例右肝管膜状狭窄者在术中应用手术器械或胆道镜扩张和取石 ;7例胆总管下段炎性狭窄进行了胆道镜扩张或支撑治疗 ;3例胆总管炎性息肉经胆道镜检查取活检并予摘除 ;7例术中胆道镜取活检证实为胆管炎患者术后予以对症治疗 ;2 4例通过术中胆道镜取活检证实为胆管癌 ,胰腺或壶腹部肿瘤患者采取了相应的手术方式。结论 :术中胆道镜的使用可以明确和纠正胆道疾病的诊断 ,减少漏诊和误诊 ,同时有助于术者选择合理的手术方式 ,使一些复杂的胆道手术变得简单合理     

胆道疾病与结肠癌的相关性研究

目前研究认为，胆道疾病如胆囊切除或胆囊结石等可能增加大肠癌发病率。胆汁酸可能通过不同的途径诱导结肠癌细胞的增殖。为进一步探讨胆道疾病与结肠癌发生的相关性，作者分析了本院普外科收治的100例结肠癌患者的临床资料，以探讨胆道疾病与结肠癌发病的相关性。     

头孢曲松钠致胆道系统药物结晶的超声诊断

目的 探讨超声检查对胆道系头孢曲松钠药物结晶的诊断价值.方法 对比分析50例无胆道系统疾病的患者,在头孢曲松钠抗炎治疗前后胆系声像图的变化.结果 50例患者使用头孢曲松钠后,胆囊壁均出现不同程度的增厚,46例胆囊腔内出现点、团状强回声,10例胆总管扩张.结论 头孢曲松钠可致胆道系统内出现类结石样药物结晶.超声对诊断胆道系统头孢曲松钠药物结晶有较高价值.     

腹腔镜联合胆道镜保胆取石术的手术配合

腹腔镜辅助胆道镜微创保胆取石治疗胆囊结石疾病,既保留了胆囊,又恢复了胆囊功能,避免了因胆囊切除所引发的并发症[1],为治疗胆囊疾病提供了一种科学的、合理的、安全的治疗方法。2010年2月～2011年6月,我院肝胆外科对78例患者实施腹腔镜联合胆道镜行保胆取石术,效果满意,     

胆囊疾病患者营养不良风险与人口学及饮食的关系分析

目的探讨胆囊疾病患者营养不良风险与人口学及饮食的关系,为营养指导提供依据。方法自行设计胆囊疾病患者营养风险与人口学及低脂饮食的关系调查表,对303例胆囊疾病患者进行调查。结果 303例患者中181例存在营养风险,经单因素及多元Logistic回归分析,胆囊疾病患者营养风险与性别、年龄、文化程度及是否低脂饮食等相关。结论胆囊疾病患者存在营养不良风险高,要根据患者个体特点进行营养指导。     

Current treatments and strategies for type 2 diabetes: can we do better with GLP-1 receptor agonists?

Abstract Diet, lifestyle modification, and pharmacotherapy with metformin are appropriate initial treatments for many patients with type 2 diabetes (T2DM). However, most individuals do not maintain glycemic control with metformin alone. Addition of other oral antidiabetes drugs (OADs), including sulfonylurea, meglitinide, or thiazolidinedione, is often the next step. Newer options, including incretin-based glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, offer important benefits as monotherapies or in combination with OADs, with low risk for hypoglycemia. Reductions in glycated hemoglobin (A1C) have been reported among patients treated with GLP-1 RAs (exenatide, -0.8 to -1.1%; liraglutide, -0.8 to -1.6%), as has weight loss (exenatide, -1.6 to -3.1 kg; liraglutide, -1.6 to -3.2 kg). GLP-1 RAs also stimulate β-cell responses and have positive effects on cardiovascular risk factors often present in patients with T2DM. The most common adverse events associated with GLP-1 RAs are nausea, which diminishes over time, and hypoglycemia (when used in combination with a sulfonylurea). A large number of trials demonstrated benefits of GLP-1 RAs, suggesting they could provide suitable treatment options for patients with T2DM.     

User’s guide to mechanism of action and clinical use of GLP-1 receptor agonists

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are injectable glucose-lowering medications approved for the treatment of adult patients with type 2 diabetes mellitus (T2DM). This article provides practical information to guide primary care physicians on the use of GLP-1RAs in patients with T2DM. Two short-acting (once- or twice-daily administration; exenatide and liraglutide) and three long-acting (weekly administration; albiglutide, dulaglutide and exenatide) GLP-1RAs are currently approved in the US. These drugs provide levels of GLP-1 receptor agonism many times that of endogenous GLP-1. The GLP-1RAs have been shown to significantly improve glycemic parameters and reduce body weight. These agents work by activating GLP-1 receptors in the pancreas, which leads to enhanced insulin release and reduced glucagon release—responses that are both glucose-dependent—with a consequent low risk for hypoglycemia. Effects on GLP-1 receptors in the CNS and the gastrointestinal tract cause reduced appetite and delayed glucose absorption due to slower gastric emptying. The most common adverse effects are gastrointestinal, which are transient and less common with the long-acting drugs. GLP-1RAs are recommended as second-line therapy in combination with metformin, sulfonylureas, thiazolidinediones or basal insulin, providing a means of enhancing glucose control while offsetting the weight gain associated with insulin and some oral agents. GLP-1RAs represent a useful tool that the primary care physician can use to help patients with T2DM achieve their therapeutic goals.     

Current treatments and strategies for type 2 diabetes: Can we do better with GLP-1 receptor agonists?

Abstract

Diet, lifestyle modification, and pharmacotherapy with metformin are appropriate initial treatments for many patients with type 2 diabetes (T2DM). However, most individuals do not maintain glycemic control with metformin alone. Addition of other oral antidiabetes drugs (OADs), including sulfonylurea, meglitinide, or thiazolidinedione, is often the next step. Newer options, including incretin-based glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, offer important benefits as monotherapies or in combination with OADs, with low risk for hypoglycemia. Reductions in glycated hemoglobin (A1C) have been reported among patients treated with GLP-1 RAs (exenatide, ?0.8 to ?1.1%; liraglutide, ?0.8 to ?1.6%), as has weight loss (exenatide, ?1.6 to ?3.1 kg; liraglutide, ?1.6 to ?3.2 kg). GLP-1 RAs also stimulate β-cell responses and have positive effects on cardiovascular risk factors often present in patients with T2DM. The most common adverse events associated with GLP-1 RAs are nausea, which diminishes over time, and hypoglycemia (when used in combination with a sulfonylurea). A large number of trials demonstrated benefits of GLP-1 RAs, suggesting they could provide suitable treatment options for patients with T2DM.     

Differentiating among incretin therapies: a multiple-target approach to type 2 diabetes

What is known and Objective: Incretin-based glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitor therapies provide glycaemic control with reduced risks associated with weight gain or hypoglycaemia. Incretin therapies are compared with their mechanisms of action, effects on haemoglobin A(1C) (HbA(1C) ), fasting plasma glucose (FPG), post-prandial glucose (PPG), body weight, β-cell function, cardiovascular biomarkers and in their safety profiles to aid clinicians in the selection of individualized pharmacotherapy for patients with type 2 diabetes. Methods: Relevant articles for a systematic review were identified through PubMed. Randomized, head-to-head comparison studies among incretin therapies were identified and included in the review. Additionally, randomized, controlled monotherapy and combination therapy studies examining glycaemic and extraglycaemic effects of individual incretin therapies from 2007 to 2011 were reviewed. Results and Discussion: Glucagon-like peptide-1 receptor agonists are generally preferred over DPP-4 inhibitors because of their greater effectiveness in reducing HbA(1C) , FPG and PPG excursions, and greater weight loss potentiation. As a monotherapy option, longer-acting GLP-1 RAs, including liraglutide and exenatide once-weekly, may be preferred at higher HbA(1C) because of their more pronounced effects on FPG. At lower/near normal HbA(1C) , a short-acting GLP-1 RA, such as exenatide twice-daily, may be a better choice as its effects are more pronounced with PPG. Ideal patients or patient situations for DPP-4 inhibitors include patients who need minimal reduction in HbA(1C,) elderly patients, patients who are unwilling or unable to take an injectable agent, when GLP-1 RAs are contraindicated or when the patient will not benefit from weight loss. Treatment benefits common to all incretin-based therapies include minimal hypoglycaemia risk, potential preservation of β-cell function and effective targeting of multiple organs underlying type 2 diabetes and of comorbidities commonly associated with type 2 diabetes, such as obesity and hypertension. What is new and Conclusion: Key differences in mechanisms of action and in glycaemic and extra-glycaemic treatment outcomes exist among incretin therapies, both within the GLP-1 RA class, and between GLP-1 RAs and DPP-4 inhibitors. Clinical judgment acknowledging important differences among incretin therapies and treatment-related patient characteristics will aid in the selection of the appropriate incretin agent for individualized pharmacotherapy.     

The Role of the Pharmacist in Managing Type 2 Diabetes with Glucagon-Like Peptide-1 Receptor Agonists as Add-On Therapy

The prevalence and associated clinical burden of type 2 diabetes (T2D) is increasing in the USA and other countries. As a consequence, the role of the pharmacist in managing T2D is expanding, and it is becoming increasingly important for pharmacists to have a complete understanding of the disease course and treatment options. Pharmacists have a key role in the use of injectable therapies, including incretin-based treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs). This article discusses the role of the pharmacist in the management of patients with T2D, particularly with respect to the use of GLP-1RAs to achieve glycemic control. GLP-1RAs are a class of injectable agents used as an adjunct to diet and exercise to improve glycemic control in adults with T2D. GLP-1RAs have been shown to lower glucose levels, slow gastric emptying, enhance satiety, and reduce body weight without increasing the risk of hypoglycemia. GLP-1RAs currently approved in the USA include exenatide twice daily, liraglutide once daily, and albiglutide, dulaglutide, and exenatide once weekly. Pharmacists can work with physicians to help identify patients for whom GLP-1RA therapy is appropriate. In addition, pharmacists can educate patients regarding medication storage, preparation, and injection techniques, glycated hemoglobin (HbA_1c) targets, pre- and post-meal blood glucose goals, adverse events and management strategies, and the long-term benefits of reducing HbA_1c. As members of the diabetes care team, pharmacists play an important role in improving patient outcomes. Funding: AstraZeneca.     

Combination therapy with SGLT-2 inhibitors and GLP-1 receptor agonists as complementary agents that address multi-organ defects in type 2 diabetes

ABSTRACT

Type 2 diabetes (T2D) has a complex pathophysiology composed of multiple underlying defects that lead to impaired glucose homeostasis and the development of macrovascular and microvascular complications. Of the currently available glucose-lowering therapies, sodium–glucose cotransporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) both provide effective glycemic control and have been shown to reduce cardiovascular (CV) events in patients with T2D and a high CV risk or established CV disease. Because these agents have complementary mechanisms of action, they are able to act on multiple defects of T2D when used in combination. This review discusses the rationale for and potential benefits of SGLT-2i plus GLP-1RA combination therapy in patients with T2D. A search of the PubMed database was conducted for studies and reviews describing the combined use of SGLT-2is and GLP-1RAs, with a specific focus on identifying clinical studies of combination therapy in patients with T2D. In clinical studies, glycated hemoglobin (A1c) was significantly reduced over 28–52 weeks with SGLT-2i plus GLP-1RA therapy versus the individual agents or baseline. Several CV risk factors, including body weight, blood pressure, and lipid parameters, were also improved. SGLT-2i plus GLP-1RA therapy was generally well tolerated, with a low risk of hypoglycemia and no unexpected findings. Taken together with results from large CV outcomes trials of SGLT-2is and GLP-1RAs, combination therapy with these agents potentially provides effective durable glycemic control and CV benefits due to their complementary actions on the defects of T2D.     

Incorporating Incretin-Based Therapies into Clinical Practice for Patients with Type 2 Diabetes

Background

Effective, evidence-based management of type 2 diabetes (T2D) requires the integration of the best available evidence with clinical experience and patient preferences.

Methods

Studies published from 2000 to 2012 evaluating glucagon-like peptide-1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) were identified using PubMed. The author contextualized the study findings with his clinical experience.

Results

Incretin-based therapy targets multiple dysfunctional organs in T2D. Injectable GLP-1RAs provide substantial glycemic control and weight reduction; while oral DPP-4 inhibitors provide moderate glycemic control and weight neutrality. Both classes are effective, well tolerated, and associated with a low incidence of hypoglycemia when used alone or in combination with other antidiabetes agents. GLP-1RAs are associated with transient nausea and, like DPP-4 inhibitors, rare pancreatitis.

Conclusion

Data indicate and clinical experience confirms that incretins are well tolerated in appropriate patients and provide sustained glycemic control and weight loss or weight neutrality throughout T2D progression.     

Albiglutide: a unique GLP-1 receptor agonist

ABSTRACT

Introduction: Albiglutide is a long acting GLP-1 receptor agonist (GLP-1 RA) administered by weekly injection.

Area covered: The pharmacokinetic and pharmacodynamic properties of albiglutide and its clinical effects are discussed. The review encompassed a search of PubMed and a thorough analysis of the European Union and US Food and Drug Administration approval documents.

Expert opinion: Albiglutide has a chemical structure quite distinct from that of other marketed GLP-1 RAs. The agent has less gastrointestinal side effects than other comparable GLP-1 RAs and is safe in patients with renal failure. As a sole treatment for diabetes and used with other hypoglycemic agents, it achieves a lowering of HbA1c of up to 1%, less than several competitor GLP-1 RAs. The benefit on weight reduction is minimal compared to other GLP-1 RAs. There exists concern about an imbalance of pancreatitis cases in the approval program as well as injection site reactions which led to discontinuance of therapy in up to 2% of participants. A large long term study now underway will determine if albiglutide, with its lower level of GI intolerance, has a place in the treatment of patients with increased risk of cardiovascular events.     

Dulaglutide for the treatment of type 2 diabetes

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are injectable agents used for the treatment of hyperglycemia in type 2 diabetes. The interest for this pharmacological class is rising with the development of once weekly compounds and the demonstration of a potential reduction in cardiorenal outcomes.

Areas covered: The paper describes the main pharmacokinetic/pharmacodynamic characteristics of dulaglutide, a new once-weekly GLP-1 RA. Dulaglutide was extensively investigated in the phase-3 AWARD program, which demonstrated its safety and efficacy when compared to placebo or active glucose-lowering agents in patients treated with diet alone, metformin or sulfonylurea monotherapy, oral dual therapies and basal insulin. In both Caucasian and Japanese patients, comparative trials showed better glucose control with dulaglutide, with a minimal risk of hypoglycemia and weight loss, but at the expense of an increased dropout rate due to side effects, mostly transient gastrointestinal disturbances. Dulaglutide proved its non-inferiority versus liraglutide and the safety and tolerance profile is similar to that of other GLP-1 RAs.

Expert opinion: The once-weekly formulation and the combined positive effects on both glucose control and weight improves patient satisfaction despite nausea. Dulaglutide must prove its capacity to reduce cardiovascular and diabetic complications in the ongoing prospective REWIND trial.     

Safety and efficacy of a glucagon-like peptide-1 receptor agonist added to basal insulin therapy versus basal insulin with or without a rapid-acting insulin in patients with type 2 diabetes: results of a meta-analysis

Objective: To consolidate the evidence from randomized controlled trials evaluating the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as add-on to basal insulin therapy in type 2 diabetes (T2D) patients.

Research design and methods: We searched the EMBASE® and NCBI PubMed (Medline) databases and relevant congress abstracts for randomized controlled trials evaluating the efficacy and safety of GLP-1 RAs as add-on to basal insulin compared with basal insulin with or without rapid-acting insulin (RAI) through 23 May 2016. The pooled data were analyzed using a random-effects meta-analysis model. A subanalysis was performed for trials investigating basal insulin plus GLP-1 RAs versus basal insulin plus RAI.

Results: Of the 2617 retrieved records, 19 randomized controlled trials enrolling 7,053 patients with T2D were included. Compared with basal insulin ± RAI, reduction in glycated hemoglobin (HbA1c) from baseline (difference in means: –0.48% [95% confidence interval (CI), –0.67 to –0.30]; p < 0.0001) and weight loss (–2.60 kg [95% CI, –3.32 to –1.89]; p < 0.0001) were significantly greater with basal insulin plus GLP-1 RA. The subanalysis similarly showed significant results for change in HbA1c from baseline and for weight loss, as well as a significantly lower risk of symptomatic hypoglycemia in patients treated with basal insulin plus GLP-1 RA versus basal insulin plus RAI (odds ratio, 0.52 [95% CI, 0.42 to 0.64]; p < 0.0001).

Conclusions: Addition of GLP-1 RA to basal insulin provided improved glycemic control, led to weight reduction and similar hypoglycemia rates versus an intensified insulin strategy; however, symptomatic hypoglycemia rates were significantly lower when compared with a basal insulin plus RAI.