好得不像真的GLP-1 受体激动剂是新的二甲双胍吗？

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Journal of diabetes and its complications Pub Date : 2024-08-30 DOI:10.1016/j.jdiacomp.2024.108851

Bernd Kowall , Gregor Maier , Wolfgang Rathmann

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引用次数: 0

摘要

最近，一项医疗保健数据库研究显示，与服用胰岛素的患者相比，服用 GLP-1 受体激动剂（GLP-1 RA）的 2 型糖尿病患者罹患 13 种肥胖相关癌症中的 10 种的风险明显较低（Wang L 等，JAMA Netw Open. 2024 7: e2421305）。据报道，某些癌症的危险比为 0.5。这不禁让人想起 10 年前发表的研究>，这些研究显示，服用二甲双胍的 2 型糖尿病患者罹患多种癌症的风险低于未服用二甲双胍的患者。在一些研究中，风险还降低了50%。二甲双胍研究中观察到的强烈效应可以用与时间相关的偏差来解释，特别是不朽时间偏差。在目前的 GLP-1 RA 研究中，令人惊讶的是，GLP-1 RA 和胰岛素使用者的几种癌症累积发病率曲线在治疗开始后立即出现了分叉。这表明很可能存在与时间相关的偏差：与 GLP-1 RA 相比，胰岛素在 2 型糖尿病更晚的阶段才开始使用。与时间有关的偏差应始终被视为一种替代解释。

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Too good to be true: Are GLP-1 receptor agonists the new metformin?

Recently, a health-care database study showed that persons with type 2 diabetes taking GLP-1 receptor agonists (GLP-1 RA) had a significantly lower risk of 10 out of 13 obesity-related cancers than patients taking insulin (Wang L, et al. JAMA Netw Open. 2024 7: e2421305). For some cancers, hazard ratios <0.5 were reported. This is reminiscent of studies published >10 years ago showing that people with type 2 diabetes taking metformin had a lower risk of many types of cancer than those not taking metformin. In some studies, also risk reductions of >50 % were reported.

The strong effects observed in the metformin studies were explained by time-related biases, in particular, immortal time bias. In the current GLP-1 RA study, it was striking that the curves for the cumulative incidence of several cancers in GLP-1 RA and insulin users diverged immediately after therapy onset. This indicates that there is most likely a time-related bias: insulin is given at much later stages of type 2 diabetes than GLP-1 RA.

The current study suggests that one should be sceptical about database results when spectacular risk reductions are reported. Time-related bias should always be considered as an alternative explanation.

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来源期刊

Journal of diabetes and its complications 医学-内分泌学与代谢

CiteScore

5.90

自引率

3.30%

发文量

153

审稿时长

16 days

期刊介绍： Journal of Diabetes and Its Complications (JDC) is a journal for health care practitioners and researchers, that publishes original research about the pathogenesis, diagnosis and management of diabetes mellitus and its complications. JDC also publishes articles on physiological and molecular aspects of glucose homeostasis. The primary purpose of JDC is to act as a source of information usable by diabetes practitioners and researchers to increase their knowledge about mechanisms of diabetes and complications development, and promote better management of people with diabetes who are at risk for those complications. Manuscripts submitted to JDC can report any aspect of basic, translational or clinical research as well as epidemiology. Topics can range broadly from early prediabetes to late-stage complicated diabetes. Topics relevant to basic/translational reports include pancreatic islet dysfunction and insulin resistance, altered adipose tissue function in diabetes, altered neuronal control of glucose homeostasis and mechanisms of drug action. Topics relevant to diabetic complications include diabetic retinopathy, neuropathy and nephropathy; peripheral vascular disease and coronary heart disease; gastrointestinal disorders, renal failure and impotence; and hypertension and hyperlipidemia.