Ostrominski John W, Aroda Vanita R, Braae Uffe C, Kruse Christian, Mandavya Kabirdev, Buse John B
Department of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA, 02115, USA.
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA, 02115, USA.
Diabetes Ther. 2025 May 22. doi: 10.1007/s13300-025-01751-6.
Treatment intensification is often required to attain glycemic targets in people living with type 2 diabetes (T2D) but can introduce regimen complexity and increase medication burden. Whether rates of treatment intensification differ by glucose-lowering medication class is unclear. This study investigated comparative treatment durability of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus standard T2D treatments, with implications for longitudinal risk mitigation and the need for treatment intensification.
This retrospective cohort study used US ambulatory electronic medical record data from January 2006 to November 2021 (covering market availability of first-generation GLP-1RAs) to assess time-to-treatment intensification following initiation of treatment with GLP-1RAs versus sodium-glucose cotransporter-2 inhibitors (SGLT2is), dipeptidyl peptidase-4 inhibitors (DPP-4is), and sulfonylureas (SUs) in 1:1 propensity score-matched adults living with T2D treated with metformin. The primary outcome was the time to treatment intensification (i.e., initiation of a third glucose-lowering medication). Secondary outcomes included change in glycated hemoglobin (HbA) level and body mass index (BMI) at 12 months after treatment initiation.
Overall, 59,958 participants were included in this study (GLP-1RA [n = 11,933], SGLT2i [n = 13,726], DPP-4i [n = 14,415], SU [n = 19,884]). Initiation of treatment with GLP-1RAs was associated with a significantly lower rate of initiation of a subsequent glucose-lowering medication compared with SGLT2is (hazard ratio [HR]: 0.93 [95% confidence interval, CI, 0.88, 0.97]; p = 0.001), DPP-4is (HR: 0.77 [95% CI 0.74, 0.81]; p < 0.001), and SUs (HR: 0.84 [95% CI 0.80, 0.88]; p < 0.001). After 12 months, GLP-1RA treatment led to a significantly greater reduction in HbA compared with SGLT2i (p = 0.005), DPP-4i (p < 0.001), and SU (p < 0.001) treatment. GLP-1RA treatment was also associated with significantly greater reductions in BMI after 12 months compared with DPP-4i and SU treatment (both p < 0.001) but not compared with SGLT2i treatment.
These data suggest that among people living with T2D treated with metformin who require a second glucose-lowering therapy, GLP-1RAs may reduce or delay the need for further treatment intensification versus other standard glucose-lowering therapies.
2型糖尿病（T2D）患者通常需要强化治疗以实现血糖目标，但这可能会增加治疗方案的复杂性并加重药物负担。目前尚不清楚降糖药物类别不同，治疗强化率是否存在差异。本研究调查了胰高血糖素样肽-1受体激动剂（GLP-1RAs）与标准T2D治疗的相对治疗持久性，这对纵向风险降低和治疗强化需求具有重要意义。
这项回顾性队列研究使用了2006年1月至2021年11月的美国门诊电子病历数据（涵盖第一代GLP-1RAs的市场供应情况），以评估在接受二甲双胍治疗的1:1倾向评分匹配的T2D成年患者中，起始使用GLP-1RAs与钠-葡萄糖协同转运蛋白-2抑制剂（SGLT2is）、二肽基肽酶-4抑制剂（DPP-4is）和磺脲类药物（SUs）治疗后至治疗强化的时间。主要结局是治疗强化时间（即开始使用第三种降糖药物）。次要结局包括治疗开始后12个月糖化血红蛋白（HbA）水平和体重指数（BMI）的变化。
本研究共纳入59,958名参与者（GLP-1RA组[n = 11,933]，SGLT2i组[n = 13,726]，DPP-4i组[n = 14,415]，SU组[n = 19,884]）。与SGLT2is相比，起始使用GLP-1RAs后开始使用后续降糖药物的发生率显著更低（风险比[HR]：0.93[95%置信区间，CI，0.88，0.97]；p = 0.001），与DPP-4is相比（HR：0.77[95%CI 0.74，0.81]；p < 0.001），与SUs相比（HR：0.84[95%CI 0.80，0.88]；p < 0.001）。治疗12个月后，与SGLT2i治疗相比（p = 0.005）、DPP-4i治疗相比（p < 0.001）和SU治疗相比（p < 0.001），GLP-1RA治疗导致HbA水平显著降低更多。与DPP-4i和SU治疗相比（均p < 0.001），GLP-1RA治疗在12个月后也与BMI显著降低更多相关，但与SGLT2i治疗相比无差异。
这些数据表明，在接受二甲双胍治疗且需要第二种降糖治疗的T2D患者中，与其他标准降糖治疗相比，GLP-1RAs可能减少或延迟进一步治疗强化的需求。
