Efficacy and safety of lixisenatide as add‐on therapy to basal insulin in older adults with type 2 diabetes in the GetGoal‐O Study. Issue 12 (26th June 2019)

• Record Type: Journal Article
• Authors: Dailey, George E.; Dex, Terry A.; Roberts, Michelle; Liu, Minzhi; Meneilly, Graydon S.
• Is Part Of: Journal of diabetes. Volume 11:Issue 12(2019)
• Page Start: 971
• Page End: 981
• Publication Date: 2019-06-26
• Subjects: lixisenatide -- older adults -- type 2 diabetes; 利西那肽 -- 老年人 -- 2型糖尿病。; Diabetes -- Periodicals; 618.3646005
• DOI: 10.1111/1753-0407.12952
• Languages: English
• ISSNs: 1753-0393

Abstract

Abstract: Background: This study compared the efficacy and safety of lixisenatide with placebo as add‐on therapy to basal insulin (BI) in adults aged ≥70 years with type 2 diabetes (T2D), with or without moderate renal insufficiency. Methods: This post hoc analysis evaluated data from non‐frail patients with T2D inadequately controlled on BI with or without oral antidiabetic drugs (n = 108), randomized to once‐daily lixisenatide 20 μg or placebo for 24 weeks (GetGoal‐O Study). The primary endpoint was the change in HbA1c from baseline to Week 24. Secondary endpoints included changes from baseline in fasting plasma glucose, 2‐hour postprandial plasma glucose (PPG), average seven‐point self‐monitored plasma glucose (SMPG), area under the curve for SMPG, daily BI dose, body weight, proportion of patients achieving HbA1c > 0.5%, and composite endpoints. Safety outcomes included the incidence of documented symptomatic hypoglycemia (plasma glucose <60 mg/dL) and gastrointestinal treatment‐emergent adverse events (TEAEs). Outcomes were also analyzed by the occurrence of moderate renal insufficiency. Results: Compared with placebo, lixisenatide‐treated patients had significantly greater reductions in HbA1c, 2‐hour PPG, average seven‐point SMPG, and body weight. Documented symptomatic hypoglycemia was approximately two‐fold higher in patients treated with placebo than lixisenatide (12.7% vs 5.7%). GI TEAEs occurred more frequently in the lixisenatide‐ than placebo‐treated group (34% vs 9.1%). Moderate renal insufficiency (estimated glomerular filtration rate between ≥30 and <60 mL/min/1.73 m 2 ) did not negatively affect lixisenatide efficacy or safety. A greater proportion of patients treated with lixisenatide than placebo achieved composite endpoints. Conclusions: Add‐on therapy with lixisenatide in non‐frail patients aged ≥70 years with T2D uncontrolled with BI is effective, safe, and well tolerated and should be considered in this population. Abstract : Highlights This post hoc analysis of the GetGoal‐O trial suggests that add‐on therapy with lixisenatide in non‐frail patients aged ≥70 years with type 2 diabetes uncontrolled on basal insulin is safe and well tolerated and should be considered in this patient population as an alternative to rapid‐acting insulin. A fixed‐ratio combination of lixisenatide and insulin glargine U100 (iGlarLixi) is available. The results suggest similar efficacy for lixisenatide in patients with moderate renal insufficiency without dose adjustment, with monitoring always advisable in this population 摘要: 背景: 这项研究在伴有或不伴中度肾功能不全的≥70岁2型糖尿病(type 2 diabetes, T2D)成人患者中, 比较了利西那肽与安慰剂作为基础胰岛素(basal insulin, BI)添加治疗的疗效及安全性。 方法: 这项事后分析所评估的数据来自经BI联合或者不联合口服降糖药治疗后血糖仍控制不佳的非脆性T2D患者(n=108), 将其随机分配至每日一次20 μg利西那肽治疗组或安慰剂组, 治疗24周(GetGoal‐O研究)。主要终点为从基线至第24周的HbA1c变化。次要终点包括空腹血糖、餐后2小时血糖、平均7点自我监测血糖(self‐monitored plasma glucose, SMPG)、SMPG曲线下面积、每日BI剂量、体重、HbA1c降幅>0.5%的患者比例以及复合终点相对于基线的变化。安全性结局包括记录的症状性低血糖(血糖<60 mg/dl)及治疗期间胃肠道不良事件(treatment‐emergent adverse events, TEAEs)的发生率。还通过中度肾功能不全的发生对结果进行了分析。 结果: 与安慰剂组相比, 利西那肽治疗组的HbA1c、餐后2小时血糖、平均7点SMPG以及体重下降均更显著。安慰剂组中记录的症状性低血糖发生率大约是利西那肽治疗组患者的2倍(分别为12.7%与5.7%)。利西那肽治疗组的胃肠道TEAEs发生率高于安慰剂组(分别为34%与9.1%)。中度肾功能不全(估算的肾小球滤过率≥30至<60 ml/min/1.73 m 2 )不会对利西那肽的疗效或安全性产生不良影响。利西那肽治疗组达到复合终点的患者比例高于安慰剂组。 结论: 在≥70岁、既往使用BI治疗后血糖仍控制不佳的非脆性T2D患者中, 加用利西那肽治疗安全有效, 而且耐受性良好, 今后在这类人群中可考虑应用这种治疗方法。