Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review.
Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review.
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DOI：
10.1038/s43856-023-00359-w
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发表时间：
2023-10-05
期刊：
影响因子：
--
通讯作者：
Dennis, John M
中科院分区：
文献类型：
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作者：
Young, Katherine G;McInnes, Eram Haider;Massey, Robert J;Kahkoska, Anna R;Pilla, Scott J;Raghavan, Sridharan;Stanislawski, Maggie A;Tobias, Deirdre K;McGovern, Andrew P;Dawed, Adem Y;Jones, Angus G;Pearson, Ewan R;Dennis, John M
2型糖尿病的精确医学方法需要识别与特定抗高血糖治疗的临床结果差异可重复相关的临床和生物学特征。这种治疗效果异质性的有力证据可以支持更个性化的2型糖尿病最佳治疗临床决策。我们对荟萃分析研究、随机对照试验和观察性研究进行了一项预先注册的系统性综述，这些研究评价了与SGLT 2抑制剂和GLP 1受体激动剂治疗的异质性治疗效应相关的临床和生物学特征，考虑了血脂、心血管和肾脏结局。在筛选了5，686项研究后，我们在最终的系统性综述中纳入了101项SGLT 2抑制剂研究和75项GLP 1受体激动剂研究。在这里，我们表明，大多数纳入的论文有方法学上的局限性，排除了治疗效果异质性的可靠评估。对于SGLT 2抑制剂，多项观察性研究表明，肾功能降低可预测低血糖反应，而胰岛素分泌减少标志物可预测GLP 1受体激动剂的低血糖反应。对于这两种治疗，随机对照试验的多项事后分析（包括试验荟萃分析）确定了心血管和肾脏结局的最小临床相关治疗效果异质性。目前关于SGLT 2抑制剂和GLP 1受体激动剂治疗疗效异质性的证据有限，可能反映了已发表研究的方法学局限性。需要稳健和适当的研究来了解2型糖尿病治疗效果的异质性，并评估精准医学的潜力，为未来的临床护理提供信息。这项研究回顾了现有证据，表明患者特征（如年龄，性别和血液检查结果）与两种最近引入的2型糖尿病药物（SGLT 2抑制剂和GLP 1受体激动剂）的不同结局相关。了解哪些个体特征与不同的反应模式相关，可以帮助临床提供者和糖尿病患者做出更明智的决定，决定哪种2型糖尿病治疗最适合个人。我们专注于三个结果：血糖水平（血糖升高是糖尿病的主要症状，糖尿病治疗的主要目的是降低血糖水平）、心脏病和肾病。我们确定了一些降低对血糖水平影响的潜在因素，包括SGLT 2抑制剂的肾功能较差和GLP 1受体激动剂的降糖激素胰岛素产量较低。我们没有发现任何一种药物改变心脏和肾脏疾病结局的明确因素。大多数研究都有局限性，这意味着需要更多的研究来充分了解影响2型糖尿病治疗结果的因素。Young，McInnes，Massey et al.系统回顾了已发表的研究，这些研究评价了SGLT 2抑制剂和GLP 1受体激动剂治疗2型糖尿病患者的异质性治疗效应相关特征。他们发现目前关于治疗效果异质性的证据有限，包括血液、心血管和肾脏结局。
A precision medicine approach in type 2 diabetes requires the identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy. We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review. Here we show that the majority of included papers have methodological limitations precluding robust assessment of treatment effect heterogeneity. For SGLT2-inhibitors, multiple observational studies suggest lower renal function as a predictor of lesser glycaemic response, while markers of reduced insulin secretion predict lesser glycaemic response with GLP1-receptor agonists. For both therapies, multiple post-hoc analyses of randomized control trials (including trial meta-analysis) identify minimal clinically relevant treatment effect heterogeneity for cardiovascular and renal outcomes. Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care. This study reviews the available evidence on which patient features (such as age, sex, and blood test results) are associated with different outcomes for two recently introduced type 2 diabetes medications: SGLT2-inhibitors and GLP1-receptor agonists. Understanding what individual characteristics are associated with different response patterns may help clinical providers and people living with diabetes make more informed decisions about which type 2 diabetes treatments will work best for an individual. We focus on three outcomes: blood glucose levels (raised blood glucose is the primary symptom of diabetes and a primary aim of diabetes treatment is to lower this), heart disease, and kidney disease. We identified some potential factors that reduce effects on blood glucose levels, including poorer kidney function for SGLT2-inhibitors and lower production of the glucose-lowering hormone insulin for GLP1-receptor agonists. We did not identify clear factors that alter heart and kidney disease outcomes for either medication. Most of the studies had limitations, meaning more research is needed to fully understand the factors that influence treatment outcomes in type 2 diabetes. Young, McInnes, Massey et al. systematically review published studies evaluating features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies in people with type 2 diabetes. They find limited current evidence on treatment effect heterogeneity, for glycaemic, cardiovascular and renal outcomes.
影响因子：
5.8
作者：
Kaku, Kohei;Wanner, Christoph;Anker, Stefan D.;Pocock, Stuart;Yasui, Atsutaka;Mattheus, Michaela;Lund, Soren S.
通讯作者：
Lund, Soren S.
DOI：
10.1007/s13300-017-0324-x
发表时间：
2017-12
期刊：
Diabetes therapy : research, treatment and education of diabetes and related disorders
影响因子：
--
作者：
Berkovic MC;Bilic-Curcic I;Herman Mahecic D;Gradiser M;Grgurevic M;Bozek T
通讯作者：
Bozek T