GLP-1 receptor agonists and the risk for cancer: A meta-analysis of randomized controlled trials.

IF 5.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Giovanni Antonio Silverii, Christian Marinelli, Costanza Bettarini, Gloria Giovanna Del Vescovo, Matteo Monami, Edoardo Mannucci
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Abstract

Aims: To assess if there is a difference in the oncogenic risk between GLP-1 RA and comparators in randomized controlled trials.

Materials and methods: A meta-analysis of randomized controlled trials comparing GLP-1RA to any comparators for diabetes and/or obesity, lasting at least 52 weeks. The endpoints included the incidence of overall cancers and single malignancies.

Results: Fifty trials were included. GLP-1RA treatment was not associated with a significant difference in risk for overall cancer (MH-OR 1.05, 95% confidence interval [CI] [0.98, 1.13]). Uterine cancer was significantly reduced in the GLP-1RA arm in trials performed in subjects with obesity (MH-OR 0.24, 95% CI [0.06, 0.94]), but not in those aimed at diabetes treatment (MH-OR 0.92, [0.58, 1.47]). We detected an increase in the risk for thyroid cancer (MH-OR 1.55, [1.05, 2.27]), more evident in longer-term trials, and in the risk for colorectal cancer (MH-OR 1.27 [1.03, 1.57]), which, conversely, was significant only in shorter-term trials. No significant difference in the risk was detected for any other cancer.

Conclusions: GLP-1 RA do not appear to produce an effect on most malignancies in clinical trials. A reduction of very close obesity-associated cancers seems possible, whereas a risk signal for thyroid cancer was observed, prompting the need for further specific studies. On the other hand, the small increase observed in colorectal cancer in shorter-term trials may be the effect of a disproportionate increase in diagnostic procedures in the GLP-1 RA arm, because of the suspicion raised by common side effects of GLP-1 RA.

GLP-1受体激动剂与癌症风险:随机对照试验的荟萃分析。
目的:在随机对照试验中评估GLP-1 RA和比较物之间的致癌风险是否存在差异。材料和方法:一项随机对照试验的荟萃分析,将GLP-1RA与糖尿病和/或肥胖的任何比较物进行比较,持续至少52周。终点包括总体癌症和单一恶性肿瘤的发病率。结果:纳入50项试验。GLP-1RA治疗与总体癌症风险的显著差异无关(MH-OR为1.05,95%可信区间[CI][0.98, 1.13])。在肥胖受试者中进行的试验中,GLP-1RA组子宫癌显著降低(MH-OR 0.24, 95% CI[0.06, 0.94]),但在糖尿病治疗组中没有(MH-OR 0.92,[0.58, 1.47])。我们发现甲状腺癌的风险增加(MH-OR为1.55,[1.05,2.27]),在长期试验中更为明显,而结直肠癌的风险增加(MH-OR为1.27[1.03,1.57]),相反,仅在短期试验中显著。没有发现其他癌症的风险有显著差异。结论:在临床试验中,GLP-1 RA似乎对大多数恶性肿瘤没有作用。减少与肥胖密切相关的癌症似乎是可能的,而甲状腺癌的风险信号被观察到,这促使需要进一步的具体研究。另一方面,在短期试验中观察到的结直肠癌的小幅增加可能是GLP-1 RA组中诊断程序不成比例增加的结果,因为GLP-1 RA的常见副作用引起了怀疑。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Diabetes, Obesity & Metabolism
Diabetes, Obesity & Metabolism 医学-内分泌学与代谢
CiteScore
10.90
自引率
6.90%
发文量
319
审稿时长
3-8 weeks
期刊介绍: Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.
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