Ochsner Diabetes Clinical Research Unit, Frank Riddick Diabetes Institute, Department of Endocrinology, Ochsner Medical Center, New Orleans, Louisiana, USA.
Novo Nordisk A/S, Søborg, Denmark.
Diabetes Obes Metab. 2021 Oct;23(10):2234-2241. doi: 10.1111/dom.14464. Epub 2021 Jul 8.
The LIRA-ADD2SGLT2i trial demonstrated that liraglutide + sodium-glucose cotransporter-2 inhibitors (SGLT2is) ± metformin significantly improved glycaemic control (not body weight) versus placebo in adults with type 2 diabetes (T2D). This post-hoc analysis assessed whether baseline characteristics influenced these findings.
LIRA-ADD2SGLT2i (NCT02964247) was a placebo-controlled, double-blind, multinational trial, wherein participants received liraglutide (≤1.8 mg/day) or placebo (randomized 2:1). Changes from baseline to week 26 in haemoglobin A1c (HbA1c), body weight and waist circumference stratified by HbA1c, body mass index (BMI), diabetes duration, duration of pre-trial SGLT2i use and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were analysed. These five baseline characteristics were divided into tertiles, and the treatment effect was evaluated using the trial product estimand.
Data from all 303 participants were analysed. There was a significant interaction between baseline HbA1c tertiles (7.0%-<7.6%; 7.6%-8.1%; ≥8.2%-9.5%) and glycaemic control at week 26 (p = .011), with the lowest HbA1c estimated treatment difference (95% confidence interval) observed in patients with lowest baseline HbA1c [-0.20% (-0.59, 0.19); -0.68% (-1.03, -0.33); -0.98% (-1.33, -0.64), respectively]. There were no significant interactions in glycaemic control across baseline BMI, diabetes duration, insulin resistance determined by HOMA-IR or SGLT2i use duration (p > .05, all). Across the five characteristics assessed, no significant interactions were found for body weight or waist circumference changes from baseline (p > .05, all).
For individuals with T2D and inadequate glycaemic control despite therapy with SGLT2is ± metformin, liraglutide 1.8 mg would provide an effective treatment intensification option, irrespective of HbA1c, BMI, diabetes duration, insulin resistance determined by HOMA-IR and SGLT2i use duration.
LIRA-ADD2SGLT2i 试验表明，利拉鲁肽联合钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）±二甲双胍可显著改善 2 型糖尿病（T2D）成人的血糖控制（而非体重），优于安慰剂。本事后分析评估了基线特征是否影响了这些发现。
LIRA-ADD2SGLT2i（NCT02964247）是一项安慰剂对照、双盲、多国试验，参与者接受利拉鲁肽（≤1.8mg/天）或安慰剂（随机 2:1）治疗。根据基线时的糖化血红蛋白（HbA1c）、体重和腰围，分析了 26 周时血红蛋白 A1c（HbA1c）、体重和腰围的变化，这些基线特征包括 HbA1c、体重指数（BMI）、糖尿病病程、试验前 SGLT2i 使用时间和稳态模型评估的胰岛素抵抗（HOMA-IR）。将这五个基线特征分为三分位，并使用试验产品估计值评估治疗效果。
对所有 303 名参与者的数据进行了分析。HbA1c 三分位（7.0%-<7.6%；7.6%-8.1%；≥8.2%-9.5%）与 26 周时的血糖控制之间存在显著交互作用（p=0.011），HbA1c 最低的估计治疗差异（95%置信区间）见于基线 HbA1c 最低的患者[-0.20%（-0.59，0.19）；-0.68%（-1.03，-0.33）；-0.98%（-1.33，-0.64）]。在 BMI、糖尿病病程、HOMA-IR 确定的胰岛素抵抗或 SGLT2i 使用时间等基线特征中，血糖控制均无显著交互作用（p>0.05，均）。在评估的五个特征中，体重或腰围从基线的变化均无显著交互作用（p>0.05，均）。
对于接受 SGLT2i±二甲双胍治疗但血糖控制仍不理想的 T2D 患者，利拉鲁肽 1.8mg 可能是一种有效的治疗强化选择，与 HbA1c、BMI、糖尿病病程、HOMA-IR 确定的胰岛素抵抗和 SGLT2i 使用时间无关。
