在无糖尿病的超重或肥胖成年人中，使用胰高血糖素样肽-1受体激动剂（GLP-1 RAs）或双重葡萄糖依赖性促胰岛素多肽/胰高血糖素样肽-1受体激动剂替尔泊肽治疗时发生主要不良心血管事件和全因死亡的风险：一项系统评价和荟萃分析
Risk of major adverse cardiovascular events and all-cause mortality under treatment with GLP-1 RAs or the dual GIP/GLP-1 receptor agonist tirzepatide in overweight or obese adults without diabetes: a systematic review and meta-analysis.
作者信息
Stefanou Maria-Ioanna, Palaiodimou Lina, Theodorou Aikaterini, Safouris Apostolos, Fischer Urs, Kelly Peter J, Dawson Jesse, Katan Mira, Katsanos Aristeidis H, Lambadiari Vaia, Giannopoulos Sotirios, Alexandrov Andrei V, Siasos Gerasimos, Tsivgoulis Georgios
机构信息
Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Stroke Unit, Metropolitan Hospital, Piraeus, Greece.
出版信息
Ther Adv Neurol Disord. 2024 Sep 25;17:17562864241281903. doi: 10.1177/17562864241281903. eCollection 2024.
BACKGROUND
Among the currently approved antiobesity medications, the glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) liraglutide and semaglutide, and the dual glucose-dependent-insulinotropic-polypeptide (GIP)/GLP-1 RA tirzepatide have been suggested to reduce cardiovascular-risk in overweight or obesity without diabetes.
OBJECTIVES
The objective of this study was to evaluate the cardio- and neuroprotective potential of these novel agents in the nondiabetic overweight/obese adult population.
DATA SOURCES AND METHODS
A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate the risk of major adverse cardiovascular events (MACE), all-cause and cardiovascular mortality in overweight or obese adults without diabetes treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). Secondary outcomes included the risk of myocardial infarction (MI) and stroke.
RESULTS
Sixteen RCTs (13 and 3 on GLP-1 RAs and tirzepatide, respectively) comprising 28,168 participants were included. GLP-1 or GIP/GLP-1 RAs reduced MACE (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.71-0.89; < 0.01; = 0) and all-cause mortality (OR: 0.80; 95% CI: 0.70-0.92; < 0.01; = 0), while there was a trend toward lower cardiovascular-mortality (OR: 0.84; 95% CI: 0.71-1.01; = 0.06; = 0%) compared to placebo. Additionally, GLP-1 or GIP/GLP-1 RAs reduced the odds of MI (OR: 0.72; 95% CI: 0.61-0.86; < 0.01; = 0%) and nonfatal-MI (OR: 0.72; 95% CI: 0.61-0.85; < 0.01; = 0%); while no associations between antiobesity treatment and fatal-MI, stroke, nonfatal, or fatal stroke were uncovered.
CONCLUSION
GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and all-cause mortality in overweight or obese adults without diabetes. Additionally, GLP-1 RAs and GIP/GLP-1 RAs attenuate the risk of MI. Since data on stroke are still limited, future RCTs are warranted to evaluate the neuroprotective potential of these novel antiobesity agents.
TRIAL REGISTRATION
PROSPERO CRD42024515966.
背景
在目前已获批的抗肥胖药物中，胰高血糖素样肽-1受体激动剂（GLP-1 RAs）利拉鲁肽和司美格鲁肽，以及双重葡萄糖依赖性促胰岛素多肽（GIP）/GLP-1 RA替尔泊肽，已被证实可降低超重或肥胖但无糖尿病患者的心血管疾病风险。
目的
本研究旨在评估这些新型药物在非糖尿病超重/肥胖成年人群中的心脏保护和神经保护潜力。
数据来源与方法
对随机对照临床试验（RCT）进行系统评价和荟萃分析，以评估接受GLP-1或GIP/GLP-1 RA治疗（对比安慰剂）的超重或肥胖但无糖尿病的成年人发生主要不良心血管事件（MACE）、全因死亡率和心血管死亡率的风险。次要结局包括心肌梗死（MI）和中风的风险。
结果
纳入了16项RCT（分别有13项关于GLP-1 RAs和3项关于替尔泊肽），共28168名参与者。GLP-1或GIP/GLP-1 RA降低了MACE（比值比（OR）：0.79；95%置信区间（CI）：0.71 - 0.89；P < 0.01；I² = 0）和全因死亡率（OR：0.80；95% CI：0.70 - 0.92；P < 0.01；I² = 0），与安慰剂相比，心血管死亡率有降低趋势（OR：0.84；95% CI：0.71 - 1.01；P = 0.06；I² = 0%）。此外，GLP-1或GIP/GLP-1 RA降低了MI的发生率（OR：0.72；95% CI：0.61 - 0.86；P < 0.01；I² = 0%）和非致命性MI的发生率（OR：0.72；95% CI：0.61 - 0.85；P < 0.01；I² = 0%）；未发现抗肥胖治疗与致命性MI、中风、非致命性或致命性中风之间存在关联。
结论
GLP-1和GIP/GLP-1 RA可降低超重或肥胖但无糖尿病成年人的心血管疾病风险和全因死亡率。此外，GLP-1 RA和GIP/GLP-1 RA可降低MI风险。由于关于中风的数据仍然有限，未来有必要进行RCT以评估这些新型抗肥胖药物的神经保护潜力。
试验注册
PROSPERO CRD42024515966
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