Noordwest Ziekenhuisgroep, Alkmaar, the Netherlands.
University of Chicago Medicine, Chicago, IL.
Diabetes Care. 2016 Dec;39(12):2304-2310. doi: 10.2337/dc16-1415. Epub 2016 Oct 14.
OBJECTIVE: To evaluate chronic kidney disease (CKD) and cardiovascular outcomes in TECOS (Clinical trial reg. no. NCT00790205, clinicaltrials.gov) participants with type 2 diabetes and cardiovascular disease treated with sitagliptin, a dipeptidyl peptidase 4 inhibitor, according to baseline estimated glomerular filtration rate (eGFR). RESEARCH DESIGN AND METHODS: We used data from 14,671 TECOS participants assigned in a double-blind design to receive sitagliptin or placebo added to existing therapy, while aiming for glycemic equipoise between groups. Cardiovascular and CKD outcomes were evaluated over a median period of 3 years, with participants categorized at baseline into eGFR stages 1, 2, 3a, and 3b (≥90, 60-89, 45-59, or 30-44 mL/min/1.73 m, respectively). RESULTS: Participants with eGFR stage 3b were older, were more often female, and had a longer duration of diabetes. Four-point major adverse cardiovascular event rates increased with lower baseline eGFR (3.52, 3.55, 5.74, and 7.34 events/100 patient-years for stages 1-3b, respectively). Corresponding adjusted hazard ratios for stages 2, 3a, and 3b versus stage 1 were 0.93 (95% CI 0.82-1.06), 1.28 (1.10-1.49), and 1.39 (1.13-1.72), respectively. Sitagliptin therapy was not associated with cardiovascular outcomes for any eGFR stage (interaction P values were all >0.44). Kidney function declined at the same rate in both treatment groups, with a marginally lower but constant eGFR difference (-1.3 mL/min/1.73 m) in those participants who were assigned to sitagliptin. Treatment differences in these eGFR values remained after adjustment for region, baseline eGFR, baseline HbA, time of assessment, and within-study HbA levels. CONCLUSIONS: Impaired kidney function is associated with worse cardiovascular outcomes. Sitagliptin has no clinically significant impact on cardiovascular or CKD outcomes, irrespective of baseline eGFR.
目的:根据基线估算肾小球滤过率(eGFR)评估患有 2 型糖尿病和心血管疾病的 TECOS(临床试验注册号 NCT00790205,clinicaltrials.gov)参与者使用二肽基肽酶 4 抑制剂西他列汀的慢性肾脏病(CKD)和心血管结局。
研究设计和方法:我们使用了 14671 名 TECOS 参与者的数据,这些参与者以双盲设计分配,接受西他列汀或安慰剂加用现有治疗,同时使两组之间的血糖达到平衡。在中位 3 年期间评估了心血管和 CKD 结局,参与者根据基线分为 eGFR 阶段 1、2、3a 和 3b(分别为≥90、60-89、45-59 和 30-44mL/min/1.73m)。
结果:eGFR 阶段 3b 的参与者年龄较大,女性更多,糖尿病病程更长。4 点主要不良心血管事件发生率随基线 eGFR 降低而升高(阶段 1-3b 的发生率分别为 3.52、3.55、5.74 和 7.34/100 患者年)。阶段 2、3a 和 3b 与阶段 1 相比的相应调整后的危害比分别为 0.93(95%CI 0.82-1.06)、1.28(1.10-1.49)和 1.39(1.13-1.72)。任何 eGFR 阶段的西他列汀治疗均与心血管结局无关(交互 P 值均>0.44)。两组的肾功能下降速度相同,接受西他列汀治疗的参与者的 eGFR 差异(-1.3mL/min/1.73m)略低但保持不变。在考虑了区域、基线 eGFR、基线 HbA、评估时间和研究内 HbA 水平后,这些 eGFR 值的治疗差异仍然存在。
结论:肾功能受损与心血管结局恶化相关。无论基线 eGFR 如何,西他列汀对心血管或 CKD 结局均无临床意义上的影响。
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