de Wit Helena M, Vervoort Gerald M M, Jansen Henry J, de Grauw Wim J C, de Galan Bastiaan E, Tack Cees J
Department of Internal Medicine 463, Section Diabetes, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, the Netherlands,
Diabetologia. 2014 Sep;57(9):1812-9. doi: 10.1007/s00125-014-3302-0. Epub 2014 Jun 20.
AIMS/HYPOTHESIS: The best treatment strategy for a patient with type 2 diabetes who shows pronounced weight gain after the introduction of insulin treatment is unclear. We determined whether addition of a glucagon-like peptide-1 (GLP-1) analogue could reverse pronounced insulin-associated weight gain while maintaining glycaemic control, and compared this with the most practised strategy, continuation and intensification of standard insulin therapy.
In a 26-week, randomised controlled trial (ELEGANT), conducted in the outpatient departments of one academic and one large non-academic teaching hospital in the Netherlands, adult patients with type 2 diabetes with ≥ 4% weight gain during short-term (≤ 16 months) insulin therapy received either open-label addition of liraglutide 1.8 mg/day (n = 26) or continued standard therapy (n = 24). A computer-generated random number list was used to allocate treatments. Participants were evaluated every 4-6 weeks for weight, glycaemic control and adverse events. The primary endpoint was between-group weight difference after 26 weeks of treatment (intention to treat).
Of 50 randomised patients (mean age 58 years, BMI 33 kg/m(2), HbA1c 7.4% [57 mmol/mol]), 47 (94%) completed the study; all patients were analysed. Body weight decreased by 4.5 kg with liraglutide and increased by 0.9 kg with standard therapy (mean difference -5.2 kg [95% CI -6.7, -3.6 kg]; p < 0.001). The respective changes in HbA1c were -0.77% (-8.4 mmol/mol) and +0.01% (+0.1 mmol/mol) (difference -0.74% [-8.1 mmol/mol]) ([95% CI -1.08%, -0.41%] [-11.8, -4.5 mmol/mol]; p < 0.001); respective changes in insulin dose were -29 U/day and +5 U/day (difference -33 U/day [95% CI -41, -25 U/day]; p < 0.001). In five patients (19%), insulin could be completely discontinued. Liraglutide was well tolerated; no severe adverse events or severe hypoglycaemia occurred.
CONCLUSIONS/INTERPRETATION: In patients with pronounced insulin-associated weight gain, addition of liraglutide to their treatment regimen reverses weight, decreases insulin dose and improves glycaemic control, and hence seems a valuable therapeutic option compared with continuation of standard insulin treatment. Trial registration ClinicalTrials.gov NCT01392898. Funding The study was funded by Novo Nordisk.
目的/假设：对于2型糖尿病患者，在开始胰岛素治疗后体重显著增加，目前尚不清楚最佳治疗策略。我们确定添加胰高血糖素样肽-1（GLP-1）类似物是否能在维持血糖控制的同时逆转与胰岛素相关的显著体重增加，并将其与最常用的策略（继续并强化标准胰岛素治疗）进行比较。
在荷兰一家学术医院和一家大型非学术教学医院的门诊进行了一项为期26周的随机对照试验（ELEGANT），短期（≤16个月）胰岛素治疗期间体重增加≥4%的2型糖尿病成年患者，接受开放标签的每日1.8 mg利拉鲁肽添加治疗（n = 26）或继续标准治疗（n = 24）。使用计算机生成的随机数字列表进行治疗分配。每4 - 6周对参与者进行体重、血糖控制和不良事件评估。主要终点是治疗26周后的组间体重差异（意向性分析）。
50名随机分组患者（平均年龄58岁，BMI 33 kg/m²，HbA1c 7.4% [57 mmol/mol]）中，47名（94%）完成研究；所有患者均纳入分析。利拉鲁肽治疗组体重下降4.5 kg，标准治疗组体重增加0.9 kg（平均差异 -5.2 kg [95% CI -6.7, -3.6 kg]；p < 0.001）。HbA1c的相应变化分别为 -0.77%（-8.4 mmol/mol）和 +0.01%（+0.1 mmol/mol）（差异 -0.74% [-8.1 mmol/mol]）（[95% CI -1.08%, -0.41%] [-11.8, -4.5 mmol/mol]；p < 0.001）；胰岛素剂量的相应变化分别为 -29 U/天和 +5 U/天（差异 -33 U/天 [95% CI -41, -25 U/天]；p < 0.001）。5名患者（19%）可完全停用胰岛素。利拉鲁肽耐受性良好；未发生严重不良事件或严重低血糖。
结论/解读：对于胰岛素相关体重显著增加的患者，在治疗方案中添加利拉鲁肽可逆转体重、降低胰岛素剂量并改善血糖控制，因此与继续标准胰岛素治疗相比似乎是一种有价值的治疗选择。试验注册ClinicalTrials.gov NCT01392898。资助本研究由诺和诺德公司资助。
