Endocrine and Metabolic Consultants, Rockville, Maryland.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
J Clin Endocrinol Metab. 2018 Jun 1;103(6):2291-2301. doi: 10.1210/jc.2018-00070.
Combination therapy with insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is important for treating type 2 diabetes (T2D). This trial assesses the efficacy and safety of semaglutide, a GLP-1RA, as an add-on to basal insulin.
To demonstrate the superiority of semaglutide vs placebo on glycemic control as an add-on to basal insulin in patients with T2D.
Phase 3a, double-blind, placebo-controlled, 30-week trial.
This study included 90 sites in five countries.
We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin.
Subcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo.
Primary endpoint was change in glycated Hb (HbA1c) from baseline to week 30. Confirmatory secondary endpoint was change in body weight from baseline to week 30.
At week 30, mean HbA1c reductions [mean baseline value, 8.4% (67.9 mmol/mol)] with semaglutide 0.5 and 1.0 mg were 1.4% (15.8 mmol/mol) and 1.8% (20.2 mmol/mol) vs 0.1% (1.0 mmol/mol) with placebo [estimated treatment difference (ETD) vs placebo, -1.35 (14.8 mmol/mol); 95% CI, -1.61 to -1.10 and ETD, -1.75% (19.2 mmol/mol); 95% CI, -2.01 to -1.50; both P < 0.0001]. Severe or blood glucose-confirmed hypoglycemic episodes were reported in 11 patients (17 events) and 14 patients (25 events) with semaglutide 0.5 and 1.0 mg, respectively, vs seven patients (13 events) with placebo (estimated rate ratio vs placebo, 2.08; 95% CI, 0.67 to 6.51 and estimated rate ratio vs placebo, 2.41; 95% CI, 0.84 to 6.96 for 0.5 and 1.0 mg; both P = nonsignificant). Mean body weight decreased with semaglutide 0.5 and 1.0 mg vs placebo from baseline to end of treatment: 3.7, 6.4, and 1.4 kg (ETD, -2.31; 95% CI, -3.33 to -1.29 and ETD, -5.06; 95% CI, -6.08 to -4.04 kg; both P < 0.0001). Premature treatment discontinuation due to adverse events was higher for semaglutide 0.5 and 1.0 mg vs placebo (4.5%, 6.1%, and 0.8%), mainly due to gastrointestinal disorders.
Semaglutide, added to basal insulin, significantly reduced HbA1c and body weight in patients with uncontrolled T2D vs placebo.
胰岛素和胰高血糖素样肽-1 受体激动剂（GLP-1RA）联合治疗对于 2 型糖尿病（T2D）的治疗非常重要。本试验评估了作为基础胰岛素附加疗法的司美格鲁肽（一种 GLP-1RA）的疗效和安全性。
证明与安慰剂相比，在 T2D 患者中，作为基础胰岛素附加疗法，司美格鲁肽在血糖控制方面具有优越性。
第 3a 阶段，双盲，安慰剂对照，30 周试验。
本研究在五个国家的 90 个地点进行。
我们研究了 397 名接受基础胰岛素联合或不联合二甲双胍稳定治疗但血糖控制不佳的 T2D 患者。
每周皮下注射司美格鲁肽 0.5 或 1.0mg 或体积匹配的安慰剂。
主要终点为从基线到第 30 周时糖化血红蛋白（HbA1c）的变化。确认性次要终点为从基线到第 30 周时体重的变化。
在第 30 周时，司美格鲁肽 0.5 和 1.0mg 的平均 HbA1c 降低（平均基线值，8.4%（67.9mmol/mol））分别为 1.4%（15.8mmol/mol）和 1.8%（20.2mmol/mol），而安慰剂为 0.1%（1.0mmol/mol）[估计治疗差异（ETD）与安慰剂相比，-1.35（14.8mmol/mol）；95%CI，-1.61 至-1.10 和 ETD，-1.75%（19.2mmol/mol）；95%CI，-2.01 至-1.50；均 P<0.0001]。与安慰剂相比，司美格鲁肽 0.5 和 1.0mg 组分别有 11 名（17 次）和 14 名（25 次）患者报告严重或血糖确认的低血糖事件，而安慰剂组有 7 名（13 次）患者（估计与安慰剂的发生率比，2.08；95%CI，0.67 至 6.51 和估计与安慰剂的发生率比，2.41；95%CI，0.84 至 6.96；均 P=无显著性差异）。与安慰剂相比，司美格鲁肽 0.5 和 1.0mg 从基线到治疗结束时体重平均下降：3.7、6.4 和 1.4kg（ETD，-2.31；95%CI，-3.33 至-1.29 和 ETD，-5.06；95%CI，-6.08 至-4.04kg；均 P<0.0001）。由于不良事件，司美格鲁肽 0.5 和 1.0mg 组提前停药的比例高于安慰剂组（4.5%、6.1%和 0.8%），主要是由于胃肠道疾病。
与安慰剂相比，在未控制的 T2D 患者中，作为基础胰岛素的附加疗法，司美格鲁肽可显著降低 HbA1c 和体重。
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