Linetzky Bruno, Sattar Naveed, Verma Subodh, Krumholz Harlan M, Xie Cathy Chang, Hoffmann Hunter T, Zimner-Rapuch Sarah, Torcello-Gómez Amelia, Stefanski Adam
Eli Lilly and Company, Indianapolis, Indiana (B.L., C.C.X., H.T.H., A.S.).
School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (N.S.).
Ann Intern Med. 2025 Aug;178(8):1095-1105. doi: 10.7326/ANNALS-24-02623. Epub 2025 Jun 24.
Tirzepatide reduced weight and improved cardiometabolic risk factors for participants in the SURMOUNT-1 trial. The changes in cardiometabolic risk factors by degree of tirzepatide-induced weight reduction across a wide spectrum of weight loss have not been reported.
To determine changes in cardiometabolic risk factors by weight reduction.
Post hoc analysis of the phase 3, randomized, double-blind, SURMOUNT-1 trial (ClinicalTrials.gov: NCT04184622).
119 sites in 9 countries.
Adults ( = 1605) with obesity, or overweight with weight-related complications (excluding diabetes), randomly assigned to tirzepatide treatment groups.
Once-weekly tirzepatide, 5, 10, or 15 mg.
Changes from baseline to week 72 in cardiometabolic risk factors by weight reduction.
Participants had a mean age of 45.4 years (SD, 12.2) and mean body mass index of 37.9 kg/m (SD, 6.7), and 68% were female. The greater weight reduction categories had higher percentages of female and White participants. Participants who lost at least 35% of their body weight from baseline to week 72 had mean changes of up to -14.2 mm Hg (95% CI, -16.1 to -12.3 mm Hg) for systolic blood pressure, -9.2 mm Hg (CI, -10.6 to -7.8 mm Hg) for diastolic blood pressure, -32.4 cm (CI, -33.5 to -31.3 cm) for waist circumference, -59.7% (CI, -63.6% to -55.3%) for the homeostatic model assessment of insulin resistance (HOMA-IR), and -0.65 percentage point (CI, -0.70 to -0.61 percentage point) for hemoglobin A. The relationship between percentage weight reduction and changes in cardiometabolic risk factors seemed mostly linear for waist circumference and blood pressure, with a steeper slope for systolic than diastolic blood pressure. Decreases in HOMA-IR and hemoglobin A were observed even with modest weight reduction, with the steepest effect occurring between less than 5% and less than 20% weight reduction. Improvements in levels of triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and non-HDL cholesterol were primarily observed only after weight reductions greater than 10%. Results were consistent after adjustment for baseline differences.
The analysis was post hoc and should be regarded as hypothesis-generating. Duration and sample size precluded evaluation of cardiovascular outcomes.
In SURMOUNT-1, tirzepatide-associated improvements in cardiometabolic risk factors positively related to the degree of weight reduction, but the pattern varied depending on outcome measure.
Eli Lilly and Company.
替尔泊肽可减轻SURMOUNT-1试验参与者的体重，并改善其心血管代谢风险因素。目前尚未报道在广泛的体重减轻范围内，替尔泊肽诱导的体重减轻程度与心血管代谢风险因素变化之间的关系。
确定体重减轻对心血管代谢风险因素的影响。
对3期随机双盲SURMOUNT-1试验（ClinicalTrials.gov：NCT04184622）进行事后分析。
9个国家的119个研究点。
患有肥胖症或超重且伴有体重相关并发症（不包括糖尿病）的成年人（n = 1605），随机分配至替尔泊肽治疗组。
每周一次注射5、10或15mg替尔泊肽。
体重减轻导致的心血管代谢风险因素从基线到第72周的变化。
参与者的平均年龄为45.4岁（标准差12.2），平均体重指数为37.9kg/m²（标准差6.7），68%为女性。体重减轻幅度越大的类别中，女性和白人参与者的比例越高。从基线到第72周体重减轻至少35%的参与者，收缩压平均变化高达-14.2mmHg（95%置信区间，-16.1至-12.3mmHg），舒张压平均变化-9.2mmHg（置信区间，-10.6至-7.8mmHg），腰围平均变化-32.4cm（置信区间，-33.5至-31.3cm），胰岛素抵抗稳态模型评估（HOMA-IR）平均变化-59.7%（置信区间，-63.6%至-55.3%），糖化血红蛋白平均变化-0.65个百分点（置信区间，-0.70至-0.61个百分点）。体重减轻百分比与心血管代谢风险因素变化之间的关系在腰围和血压方面似乎大多呈线性，收缩压的斜率比舒张压更陡。即使体重适度减轻，HOMA-IR和糖化血红蛋白也会降低，在体重减轻不足5%至不足20%之间降幅最大。甘油三酯、高密度脂蛋白（HDL）胆固醇、低密度脂蛋白胆固醇和非HDL胆固醇水平的改善主要在体重减轻超过10%后才观察到。调整基线差异后结果一致。
该分析为事后分析，应视为产生假设。研究持续时间和样本量妨碍了对心血管结局的评估。
在SURMOUNT-1试验中，替尔泊肽相关的心血管代谢风险因素改善与体重减轻程度呈正相关，但模式因结局指标而异。
礼来公司。
