The effects of glucagon-like peptide-1 on the beta cell

Type 2 diabetes is a progressive disease characterized by insulin resistance and impaired beta-cell function. Treatments that prevent further beta-cell decline are therefore essential for the management of type 2 diabetes. Glucagon-like peptide-1 (GLP-1) is an incretin hormone that is known to stimulate glucose-dependent insulin secretion. Furthermore, GLP-1 appears to have multiple positive effects on beta cells. However, GLP-1 is rapidly degraded by dipeptidyl peptidase-4 (DPP-4), which limits the clinical relevance of GLP-1 for the treatment of type 2 diabetes. Two main classes of GLP-1-based therapies have now been developed: DPP-4 inhibitors and GLP-1 receptor agonists. Liraglutide and exenatide are examples of GLP-1 receptor agonists that have been developed to mimic the insulinotropic characteristics of endogenous GLP-1. Both have demonstrated improved beta-cell function in patients with type 2 diabetes, as assessed by homoeostasis model assessment-B analysis and proinsulin : insulin ratio. Additionally, liraglutide and exenatide are able to enhance first- and second-phase insulin secretion and are able to restore beta-cell sensitivity to glucose. Preclinical studies have shown that both liraglutide and exenatide treatment can increase beta-cell mass, stimulate beta-cell proliferation, increase beta-cell neogenesis and inhibit beta-cell apoptosis. Clinical studies are needed to confirm these findings in humans. Replication of these data in humans could have important clinical implications for the treatment of type 2 diabetes.     

利拉鲁肽对2型糖尿病轻度认知功能障碍患者炎性因子及认知功能的影响

目的：探讨利拉鲁肽对2型糖尿病轻度认知功能障碍患者炎性因子及认知功能的影响。方法：选取使用门冬胰岛素30治疗的2型糖尿病（T2DM）伴轻度认知功能障碍（MCI）患者86例，分为治疗组（43例）与对照组（43例），疗程1年。对照组维持原门冬胰岛素30治疗，治疗组改为利拉鲁肽治疗。治疗前和治疗12，24，36，48周末测定患者身高、体质量、血压水平，计算体重指数（BMI），并记录血糖达标[糖化血红蛋白（Hb A1c）≤ 8%]、低血糖情况、实验室检查（血糖、糖化血红蛋白、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子（TNF-α）水平），并采用简易精神状态量表（MMSE）、蒙特利尔认知量表（MoCA）评估认知功能。结果：对照组和治疗组各完成42例和41例。治疗12，24，36，48周末，治疗组IL-1β、IL-6、TNF-α水平显著低于对照组（P< 0.01），36，48周末HbA1c水平低于对照组（P<0.05），MMSE及MoCA量表评分高于对照组（P<0.05）。对照组和治疗组血糖达标率分别为76.19%（32/42）和82.93%（34/41），痴呆发生率均为0，差异均无显著意义（P>0.05）；低血糖发生率分别为59.52%（25/42）和7.32%（3/41），治疗组低于对照组（P<0.01）。结论：和门冬胰岛素30相比，利拉鲁肽治疗2型糖尿病MCI患者，能更好地控制FPG、2hPG、HbA1c，降低炎性因子水平（IL-1β、IL-6、TNF-α），低血糖发生率更低，并能改善患者认知功能。     

Treatment potential of the GLP-1 receptor agonists in type 2 diabetes mellitus: a review

Over the last decade, the discovery of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) has increased the treatment options for patients with type 2 diabetes mellitus (T2DM). GLP-1 RAs mimic the effects of native GLP-1, which increases insulin secretion, inhibits glucagon secretion, increases satiety and slows gastric emptying. This review evaluates the phase III trials for all approved GLP-1 RAs and reports that all GLP-1 RAs decrease HbA1c, fasting plasma glucose, and lead to a reduction in body weight in the majority of trials. The most common adverse events are nausea and other gastrointestinal discomfort, while hypoglycaemia is rarely reported when GLP-1 RAs not are combined with sulfonylurea or insulin. Treatment options in the near future will include co-formulations of basal insulin and a GLP-1 RA.     

利拉鲁肽治疗超重、肥胖2型糖尿病并肾脏疾病的临床观察

目的 观察利拉鲁肽治疗超重、肥胖2型糖尿病(type 2 dabetes mellitus,T2DM)并肾脏疾病的临床效果.方法 筛选超重、肥胖T2DM患者70例,糖化血红蛋白(glycated hemoglobin,HbA1c)符合(7％≤HbA1c≤11％),随机分成2组,胰岛素联合二甲双胍和(或)阿卡波糖组(胰岛...     

基于FAERS数据库利拉鲁肽不良反应信号挖掘与分析

目的： 通过对利拉鲁肽不良反应信号的挖掘分析,为临床合理安全用药提供依据。方法： 采用比例失衡法中的报告比值比法（ROR）和比例报告比值比法（PRR）对美国FDA不良事件报告系统（FAERS）利拉鲁肽2010年一季度至2019年一季度共37个季度的不良反应报告进行数据挖掘及分析。结果： 共收集到56 396条药品不良反应（Adverse Drug Reaction,ADR）报告,合并同义词后使用ROR与PRR法,经过二次筛选,得到ADR信号87个,主要集中于胃肠道系统损害、代谢和营养障碍、用药部位损害、内分泌紊乱等方面。结论： 对利拉鲁肽ADR信号进行挖掘和分析,为临床安全用药提供参考,采取相应的预防措施,或避免应用于高风险人群。     

Fixed-ratio combination therapy for type 2 diabetes: the top ten things you should know about insulin and glucagon-like peptide-1 receptor agonist combinations

Many individuals with type 2 diabetes (T2D) will eventually require insulin therapy to help achieve and maintain adequate glycemic control. However, the use of insulin can be associated with adverse effects such as hypoglycemia and weight gain, and in some patients the addition of insulin to treatment regimens is often still insufficient to achieve target glycemic control. Combining basal insulin with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of patients with T2D has been demonstrated to be effective and well tolerated, while mitigating many of the adverse events associated with giving either of these drug classes alone. Two titratable, fixed-ratio combination therapies, iGlarLixi and IDegLira, that combine basal insulin and a GLP-1 RA in a once-daily subcutaneous injection are currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with T2D. The fixed-ratio combination iGlarLixi combines insulin glargine 100 Units/mL with lixisenatide, while IDegLira combines insulin degludec 100 Units/mL with liraglutide. While these new fixed-ratio combinations contain antihyperglycemic medications that are familiar to most health care providers, there are many questions relating to their use when formulated as a fixed-ratio combination therapy. This article discusses the ‘top 10’ considerations that health care providers should know about these novel combination therapies as these agents begin to gain an increasing presence in clinical practice.