二肽基肽酶 4 抑制剂早期治疗可降低 2 型糖尿病患者的血糖变异性并延迟胰岛素起始治疗：一项倾向评分匹配队列研究。
Early treatment with dipeptidyl-peptidase 4 inhibitors reduces glycaemic variability and delays insulin initiation in type 2 diabetes: A propensity score-matched cohort study.
机构信息
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
出版信息
Diabetes Metab Res Rev. 2024 Jan;40(1):e3711. doi: 10.1002/dmrr.3711. Epub 2023 Aug 26.
AIMS
To examine whether early treatment intensification using dipeptidyl-peptidase 4 inhibitors (DPP4i) delays insulin initiation in Chinese patients diagnosed with type 2 diabetes for less than 5 years.
MATERIALS AND METHODS
In a territory-wide prospective cohort study, patients with type 2 diabetes initiating DPP4i at diabetes duration <2 years (early intensification) and 3-5 years (late intensification) were matched using 1:1 propensity-score matching (n = 908 in each arm). We used Cox regression to compare the risk of insulin initiation between the two groups. We explored the interactive and mediation effects of glycated haemoglobin (HbA1c) variability score (HVS), defined as the percentage of HbA1c varying by ≥0.5% compared with preceding values.
RESULTS
Of 1816 patients (60.7% men, mean age 54.4 ± 11.9 years), 92.4% and 71.9% were treated with metformin and sulphonylureas respectively at DPP4i initiation. Early DPP4i intensification [hazard ratio (HR) 0.71, (95% CI 0.58-0.68)] and low HVS (<50%) (HR = 0.40, 0.33-0.50) were associated with delayed insulin initiation during a median 4.08 years of follow-up. Early intensification with low HVS had the lowest risk versus late intensification with high HVS (HR = 0.30, 0.22-0.40) (p = 0.013). HVS mediated 19.5% of the total effect of early DPP4i intensification on delaying insulin initiation. The late and early intensification groups had similar HbA1c at month 0 (8.4 ± 1.3% vs. 8.4 ± 1.5%) and month 3 (7.6 ± 1.2% vs. 7.6 ± 1.3%) after DPP4i initiation. By month 12, HbA1c in the late intensification group deteriorated (7.9 ± 1.4%) but remained stable in the early intensification group (7.6 ± 1.4%, p = 0.001) with persistent between-group difference over 72 months (8.2 ± 1.7% vs. 7.7 ± 1.6%, p = 0.001).
CONCLUSIONS
In type 2 diabetes, early DPP4i intensification delayed insulin initiation, partially explained by reduced glycaemic variability.
目的
探讨在糖尿病病程不足 5 年的中国 2 型糖尿病患者中，早期使用二肽基肽酶-4 抑制剂（DPP4i）强化治疗是否会延迟胰岛素的起始使用。
材料和方法
在一项全港范围内的前瞻性队列研究中，将糖尿病病程<2 年（早期强化）和 3-5 年（晚期强化）时起始 DPP4i 治疗的患者采用 1:1 倾向评分匹配（每组 908 例）。采用 Cox 回归比较两组胰岛素起始的风险。我们还探讨了糖化血红蛋白（HbA1c）变异性评分（HVS）的交互和中介作用，该评分定义为与前一次相比 HbA1c 变化≥0.5%的百分比。
结果
在 1816 例患者（60.7%为男性，平均年龄 54.4±11.9 岁）中，起始 DPP4i 治疗时分别有 92.4%和 71.9%的患者使用二甲双胍和磺脲类药物。早期 DPP4i 强化治疗（风险比[HR]0.71，95%置信区间 0.58-0.68）和低 HVS（<50%）（HR=0.40，0.33-0.50）与中位随访 4.08 年期间胰岛素起始的延迟相关。早期强化治疗且 HVS 较低与晚期强化治疗且 HVS 较高相比，胰岛素起始的风险最低（HR=0.30，0.22-0.40）（p=0.013）。HVS 解释了早期 DPP4i 强化治疗对延迟胰岛素起始的总效应的 19.5%。在起始 DPP4i 后第 0 个月（8.4±1.3%比 8.4±1.5%）和第 3 个月（7.6±1.2%比 7.6±1.3%），晚期和早期强化治疗组的 HbA1c 水平相似。在第 12 个月时，晚期强化组的 HbA1c 恶化（7.9±1.4%），而早期强化组则保持稳定（7.6±1.4%，p=0.001），72 个月时两组间仍存在持续性差异（8.2±1.7%比 7.7±1.6%，p=0.001）。
结论
在 2 型糖尿病患者中，早期 DPP4i 强化治疗延迟了胰岛素的起始使用，部分原因是降低了血糖变异性。
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