Drug Information Services, Kaiser Permanente California Regions, Oakland, CA.
Pharmacy Program, Cedars-Sinai Medical Network, Los Angeles, CA.
Perm J. 2020 Nov;24:1-8. doi: 10.7812/TPP/19.224.
Guidelines do not make clear recommendations for third add-on agents to metformin plus a sulfonylurea. This study compared the effectiveness and safety of dipeptidyl peptidase-4 inhibitors (DPP4is) to thiazolidinedione (TZD) or insulin as a third add-on agent to metformin plus a sulfonylurea in an integrated health care setting.
This retrospective database cohort study included adults with type 2 diabetes not at goal hemoglobin A (HbA) who initiated DPP4i, TZD, or insulin as a third add-on agent to metformin plus a sulfonylurea from January 2006 to June 2016. Primary outcomes were the proportion of patients who achieved goal HbA after starting the third add-on agent and change in HbA. Subgroup analysis was performed for patients with baseline HbA greater than 9%.
In this study, 2080 patients started on a DPP4i were matched to 8320 patients started on TZD and to 8320 patients taking insulin. A significantly higher percentage of patients taking TZD reached goal HbA (31.0% versus 23.6%; p < 0.05) and had a significantly larger HbA reduction (-0.94% ± 1.34% versus -0.79% ± 1.23%; p < 0.01) compared to patients taking a DPP4i. No difference in the percentage of patients meeting goal HbA nor in change in HbA was demonstrated between insulin versus DPP4i regimens. For patients with baseline HbA greater than 9%, insulin or TZD resulted in a significantly higher proportion of patients achieving goal HbA compared to DPP4i (17.3% and 19.0% versus 12.4%, respectively; p < 0.01).
TZD was more effective than DPP4i but DPP4i was as effective as insulin as a third add-on agent in the overall study population. Insulin was more effective than DPP4i only in the subgroup analysis of patients with baseline HbA greater than 9%.
指南并未明确推荐将二甲双胍与磺酰脲类药物联合应用的第三种附加药物。本研究在综合性医疗保健环境中，比较了二肽基肽酶-4 抑制剂（DPP4i）与噻唑烷二酮（TZD）或胰岛素作为二甲双胍与磺酰脲类药物联合应用的第三种附加药物在疗效和安全性方面的差异。
本回顾性数据库队列研究纳入了自 2006 年 1 月至 2016 年 6 月期间起始使用 DPP4i、TZD 或胰岛素作为二甲双胍与磺酰脲类药物联合应用的第三种附加药物的 2 型糖尿病患者，这些患者的糖化血红蛋白（HbA）未达标。主要结局为起始第三种附加药物后达到目标 HbA 的患者比例以及 HbA 的变化。对基线 HbA 大于 9%的患者进行了亚组分析。
本研究中，2080 例起始 DPP4i 的患者与 8320 例起始 TZD 的患者和 8320 例起始胰岛素的患者相匹配。起始 TZD 的患者达到目标 HbA 的比例明显更高（31.0% vs. 23.6%；p < 0.05），且 HbA 降低幅度更大（-0.94% ± 1.34% vs. -0.79% ± 1.23%；p < 0.01），与起始 DPP4i 的患者相比。起始胰岛素或 DPP4i 的患者在达到目标 HbA 的患者比例和 HbA 变化方面无差异。对于基线 HbA 大于 9%的患者，与 DPP4i 相比，胰岛素或 TZD 使更多患者达到目标 HbA（分别为 17.3%和 19.0% vs. 12.4%；p < 0.01）。
在总体研究人群中，TZD 比 DPP4i 更有效，但 DPP4i 与胰岛素作为第三种附加药物的疗效相同。在基线 HbA 大于 9%的亚组分析中，胰岛素比 DPP4i 更有效。
