Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Johns Hopkins School of Nursing, Baltimore, MD, USA.
Nat Med. 2023 Nov;29(11):2909-2918. doi: 10.1038/s41591-023-02597-w. Epub 2023 Oct 15.
The effects of tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, on weight reduction after successful intensive lifestyle intervention are unknown. This double-blind, placebo-controlled trial randomized (1:1) adults with body mass index ≥30 or ≥27 kg/m and at least one obesity-related complication (excluding diabetes), who achieved ≥5.0% weight reduction after a 12-week intensive lifestyle intervention, to tirzepatide maximum tolerated dose (10 or 15 mg) or placebo once weekly for 72 weeks (n = 579). The treatment regimen estimand assessed effects regardless of treatment adherence in the intention-to-treat population. The coprimary endpoint of additional mean per cent weight change from randomization to week 72 was met with changes of -18.4% (standard error (s.e.) 0.7) with tirzepatide and 2.5% (s.e. 1.0) with placebo (estimated treatment difference -20.8 percentage points (95% confidence interval (CI) -23.2%, -18.5%; P < 0.001). The coprimary endpoint of the percentage of participants achieving additional weight reduction ≥5% was met with 87.5% (s.e. 2.2) with tirzepatide and 16.5% (s.e. 3.0) with placebo achieving this threshold (odds ratio 34.6%; 95% CI 19.2%, 62.6%; P < 0.001). The most common adverse events with tirzepatide were gastrointestinal, with most being mild to moderate in severity. Tirzepatide provided substantial additional reduction in body weight in participants who had achieved ≥5.0% weight reduction with intensive lifestyle intervention. ClinicalTrials.gov registration: NCT04657016 .
替西帕肽是一种葡萄糖依赖性胰岛素促分泌多肽和胰高血糖素样肽-1 受体激动剂，其在成功进行强化生活方式干预后对体重减轻的影响尚不清楚。这项双盲、安慰剂对照试验将（1:1）随机分组，纳入体质指数（BMI）≥30 或≥27kg/m2 且至少有一种肥胖相关并发症（不包括糖尿病）的成年人，这些患者在经过 12 周强化生活方式干预后体重减轻≥5.0%，接受替西帕肽最大耐受剂量（10 或 15mg）或安慰剂每周一次，共 72 周（n=579）。意向治疗人群中，无论治疗依从性如何，治疗估计值都评估了疗效。从随机分组到第 72 周的体重额外平均百分比变化的主要复合终点达到了-18.4%（标准误差（s.e.）0.7），替西帕肽组和安慰剂组分别为-20.8%（95%置信区间（CI）-23.2%，-18.5%；P<0.001）。体重减轻≥5%的参与者比例达到主要复合终点，替西帕肽组为 87.5%（s.e. 2.2），安慰剂组为 16.5%（s.e. 3.0）（比值比 34.6%；95%CI 19.2%，62.6%；P<0.001）。替西帕肽最常见的不良事件是胃肠道事件，大多数为轻度至中度。替西帕肽为那些通过强化生活方式干预已达到体重减轻≥5.0%的参与者提供了显著的额外体重减轻。临床试验.gov 注册：NCT04657016。
