Patient stratification for determining optimal second-line and third-line therapy for type 2 diabetes: the TriMaster study.
Patient stratification for determining optimal second-line and third-line therapy for type 2 diabetes: the TriMaster study.
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DOI：
10.1038/s41591-022-02120-7
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发表时间：
2023-03
期刊：
影响因子：
82.9
通讯作者：
TriMaster Study group
中科院分区：
文献类型：
--
作者：
Shields BM;Dennis JM;Angwin CD;Warren F;Henley WE;Farmer AJ;Sattar N;Holman RR;Jones AG;Pearson ER;Hattersley AT;TriMaster Study group
精准医学的目标是根据个人的临床特征进行治疗。一种不同的药物反应，对于使用这些特征进行治疗选择至关重要，从未在2型糖尿病中被直接检查过。我们检验了两个假设：1)体重指数为30 kg/m2的个体，与体重指数为30 kg/m2的≤相比，噻唑烷二酮类药物的降糖作用大于DPP4抑制剂；2)EGFR60-90mls/min/1.73m2的个体与EGFR&Gt；90mls/min/1.73m2相比，DPP4抑制剂的降糖作用大于SGLT2抑制剂。这两个假设的主要终点是两种药物在不同阶层之间实现的HbA1c差异。525名2型糖尿病患者参加了一项设在英国的随机、双盲、三方交叉试验，为期16周，每天服用西格列汀100毫克、卡那格列津100毫克和吡格列酮30毫克，单独服用二甲双胍或二甲双胍加磺脲。总体而言，三种药物吡格列酮59.6 mm o l/m o l、西格列汀60.0 m o l/m o l、卡那格列酮60.6 m o l/m ol获得的HbA1c相似(p=0.2)。体重指数为30 kg/m2的受试者，与体重指数为30 kg/m2的受试者相比，吡格列酮的糖化血红蛋白降低2.88≤(95%可信区间0.98，4.79)(n=356，P=0.003)。EGFR60~90mls/min/1.73m2的受试者，与EGFR90mls/min/1.73m2的受试者相比，西格列汀的HbA1c降低2.90 mmoL/m ol(95%CI 1.19，4.61)(n=342，P=0.001)。报告了2201个不良事件，其中447/525(85%)随机参与者在至少一种研究药物上经历了不良事件。在这项针对2型糖尿病的精确医学试验中，我们的发现支持使用简单的常规临床措施来确定最有可能为给定患者提供最大降糖效果的药物类别。ClinicalTrials.gov注册：NCT02653209；ISRCTN注册：12039221.
Precision medicine aims to treat an individual based on their clinical characteristics. A differential drug response, critical to using these features for therapy selection, has never been examined directly in type 2 diabetes. We tested two hypotheses: 1) individuals with BMI>30kg/m2, compared with BMI ≤30kg/m2, have greater glucose lowering with thiazolidinediones than DPP4-inhibitors, and 2) individuals with eGFR 60-90mls/min/1.73m2 compared with eGFR >90mls/min/1.73m2 have greater glucose lowering with DPP4-inhibitors than SGLT2-inhibitors. The primary endpoint for both hypotheses was the achieved HbA1c difference between strata for the two drugs. 525 people with type 2 diabetes participated in a UK based randomised, double-blind, three-way crossover trial of 16 weeks treatment with each of sitagliptin 100mg/day, canagliflozin 100mg/day and pioglitazone 30mg/day added to metformin alone or metformin plus sulfonylurea. Overall, the achieved HbA1c was similar for the three drugs pioglitazone 59.6 mmol/mol, sitagliptin 60.0 mmol/mol, canagliflozin 60.6 mmol/mol (p=0.2). Participants with BMI>30kg/m2, compared with BMI≤30kg/m2, had a 2.88 mmol/mol (95% CI 0.98,4.79) lower HbA1c on pioglitazone than on sitagliptin (n=356, P=0.003). Participants with eGFR 60-90mls/min/1.73m2, compared with eGFR >90mls/min/1.73m2, had a 2.90 mmol/mol (95% CI 1.19,4.61) lower HbA1c on sitagliptin than on canagliflozin (n=342, P=0.001). There were 2201 adverse events reported, and 447/525 (85%) randomised participants experienced an adverse event on at least one of the study drugs. In this precision medicine trial in type 2 diabetes, our findings support the use of simple routinely available clinical measures to identify the drug class most likely to deliver the greatest glycaemic reduction for a given patient. ClinicalTrials.gov registration: NCT02653209; ISRCTN registration12039221..
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影响因子：
3.2
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通讯作者：
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通讯作者：
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