Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London and Imperial College Healthcare NHS Trust, London, UK.
Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London and Imperial College Healthcare NHS Trust, London, UK; Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin, Ireland.
Lancet Diabetes Endocrinol. 2019 Jul;7(7):549-559. doi: 10.1016/S2213-8587(19)30157-3. Epub 2019 Jun 4.
Many patients with type 2 diabetes do not achieve sustained diabetes remission after metabolic (bariatric) surgery for the treatment of obesity. Liraglutide, a glucagon-like peptide-1 analogue, improves glycaemic control and reduces bodyweight in patients with type 2 diabetes. Our aim was to assess the safety and efficacy of liraglutide 1·8 mg in patients with persistent or recurrent type 2 diabetes after metabolic surgery.
In the GRAVITAS randomised double-blind, placebo-controlled trial, we enrolled adults who had undergone Roux-en-Y gastric bypass or vertical sleeve gastrectomy and had persistent or recurrent type 2 diabetes with HbA levels higher than 48 mmol/mol (6·5%) at least 1 year after surgery from five hospitals in London, UK. Participants were randomly assigned (2:1) via a computer-generated sequence to either subcutaneous liraglutide 1·8 mg once daily or placebo, both given together with a reduced-calorie diet, aiming for a 500 kcal per day deficit from baseline energy intake, and increased physical activity. The primary outcome was the change in HbA from baseline to the end of the study period at 26 weeks, assessed in patients who completed the trial. Safety was assessed in the safety analysis population, consisting of all participants who received either liraglutide or placebo. This trial is registered with EudraCT, number 2014-003923-23, and the ISRCTN registry, number ISRCTN13643081.
Between Jan 29, 2016, and May 2, 2018, we assigned 80 patients to receive either liraglutide (n=53) or placebo (n=27). 71 (89%) participants completed the study and were included in the principal complete-cases analysis. In a multivariable linear regression analysis, with baseline HbA levels and surgery type as covariates, liraglutide treatment was associated with a difference of -13·3 mmol/mol (-1·22%, 95% CI -19·7 to -7·0; p=0·0001) in HbA change from baseline to 26 weeks, compared with placebo. Type of surgery had no significant effect on the outcome. 24 (45%) of 53 patients assigned to liraglutide and 11 (41%) of 27 assigned to placebo reported adverse effects: these were mainly gastrointestinal and in line with previous experience with liraglutide. There was one death during the study in a patient assigned to the placebo group, which was considered unrelated to study treatment.
These findings support the use of adjunctive liraglutide treatment in patients with persistent or recurrent type 2 diabetes after metabolic surgery.
JP Moulton Foundation.
许多 2 型糖尿病患者在接受代谢（减重）手术后治疗肥胖症，无法持续缓解糖尿病。利拉鲁肽是一种胰高血糖素样肽-1 类似物，可改善 2 型糖尿病患者的血糖控制并减轻体重。我们旨在评估利拉鲁肽 1.8mg 对代谢手术后持续或复发 2 型糖尿病患者的安全性和有效性。
在 GRAVITAS 随机双盲、安慰剂对照试验中，我们招募了在英国伦敦的五家医院接受过 Roux-en-Y 胃旁路术或垂直袖状胃切除术的成年人，这些患者在手术后至少 1 年患有持续或复发的 2 型糖尿病，HbA 水平高于 48mmol/mol（6.5%）。参与者通过计算机生成的序列以 2:1 的比例随机分配至皮下利拉鲁肽 1.8mg 每日一次或安慰剂，两者均与低热量饮食一起使用，目标是从基线能量摄入中每天减少 500 卡路里，增加身体活动。主要结局是在 26 周的研究期末从基线到 HbA 的变化，在完成试验的患者中进行评估。安全性在安全性分析人群中进行评估，该人群由接受利拉鲁肽或安慰剂的所有参与者组成。该试验在 EudraCT 注册，编号为 2014-003923-23，在 ISRCTN 注册，编号为 ISRCTN13643081。
2016 年 1 月 29 日至 2018 年 5 月 2 日，我们将 80 名患者分配至接受利拉鲁肽（n=53）或安慰剂（n=27）。71 名（89%）参与者完成了研究并被纳入主要完整病例分析。在多变量线性回归分析中，以基线 HbA 水平和手术类型为协变量，与安慰剂相比，利拉鲁肽治疗与 HbA 从基线到 26 周的变化差异为 -13.3mmol/mol（-1.22%，95%CI -19.7 至 -7.0；p=0.0001）相关。手术类型对结果没有显著影响。53 名接受利拉鲁肽治疗的患者中有 24 名（45%）和 27 名接受安慰剂治疗的患者中有 11 名（41%）报告了不良反应：这些不良反应主要是胃肠道的，与利拉鲁肽以往的经验一致。在接受安慰剂治疗的患者中有 1 人在研究期间死亡，被认为与研究治疗无关。
这些发现支持在代谢手术后持续或复发 2 型糖尿病患者中使用辅助利拉鲁肽治疗。
JP Moulton 基金会。
