OBJECTIVE This objective of this study was to estimate and explain the gap between clinical efficacy and real-world (RW) effectiveness of type 2 diabetes medications.

RESEARCH DESIGN AND METHODS This mixed-methods quasi-experimental study used retrospective claims (Optum/Humedica) to compare the change in HbA_1c of RW patients with type 2 diabetes 12 months after starting a glucagon-like peptide-1 receptor agonist (GLP-1RA) or dipeptidyl peptidase-4 inhibitor (DPP4) with published findings from randomized controlled trials (RCTs) evaluating these drugs. Selected RW patients were similar to RCT patients, and regression analysis was used in the RW data to adjust for differences between poorly adherent and adherent patients to explain why RCT and RW findings may differ.

RESULTS RW patients initiating a GLP-1RA (n = 221) or a DPP4 (n = 652) experienced smaller reductions in HbA_1c (GLP-1RA: −0.52% [−6 mmol/mol], DPP4: −0.51% [−6 mmol/mol])than reported in RCTs (−1.30% [−14 mmol/mol] from seven GLP-1RA RCTs, n = 2,600; −0.68% [−8 mmol/mol] from four DPP4 RCTs, n = 1,889). Baseline HbA_1c, additional medications, and adherence were significant explanatory factors in the RW HbA_1c change. Modeled estimates of RCT efficacy (−1.04% GLP-1RA [−12 mmol/mol], −0.69% DPP4 [−8 mmol/mol]) were within the RCTs’ reported range (GLP-1RA: −0.84% to −1.60% [−9 to −18 mmol/mol]; DPP4: −0.47% to −0.90% [−5 to −10 mmol/mol]). Poor medication adherence accounted for approximately three-fourths of the gap between RW and expected RCT results (gap = 0.51% [6 mmol/mol] GLP1-RA; 0.18% [3 mmol/mol] DPP4).

CONCLUSIONS Poor medication adherence is primarily why RW effectiveness is significantly less than RCT efficacy, suggesting an urgent need to effectively address adherence among patients with type 2 diabetes.

目的本研究的目的是评估和解释2型糖尿病药物的临床疗效与实际疗效之间的差距。

研究设计和方法将这种混合的方法准实验研究中使用回顾性要求（Optum / Humedica）比较在HBA上的变化_1C起始胰高血糖素样肽-1受体激动剂（GLP-12个月后RW患者的2型糖尿病1RA）或二肽基肽酶4抑制剂（DPP4），其中已公开评估这些药物的随机对照试验（RCT）的发现。选择的RW患者与RCT患者相似，并且在RW数据中使用回归分析来调整依从性差和依从性患者之间的差异，以解释为什么RCT和RW结果可能有所不同。

结果发起GLP-1RA（n = 221）或DPP4（n = 652）的RW患者的HbA _1c降低幅度较小（GLP-1RA：-0.52％[−6 mmol / mol]，DPP4：-0.51％[- 6毫摩尔/摩尔]）超过了RCT中的报告（七个GLP-1RA RCT，-1.30％[−14 mmol / mol]，n = 2,600；四个DPP4 RCT，-0.68％[−8 mmol / mol]，n = 1,889 ）。基线HbA _1c，其他药物和依从性是RW HbA _1c的重要解释因素改变。RCT功效的模型估计值（−1.04％GLP-1RA [−12 mmol / mol]，− 0.69％DPP4 [−8 mmol / mol]）在RCT报告的范围内（GLP-1RA：−0.84％至-1.60 ％[-9至-18 mmol / mol]； DPP4：-0.47％至-0.90％[-5至-10 mmol / mol]）。药物依从性差约占RW和预期RCT结果之间的差距的四分之三（差距= 0.51％[6 mmol / mol] GLP1-RA； 0.18％[3 mmol / mol] DPP4）。

结论药物依从性差的主要原因是RW疗效显着低于RCT疗效的原因，这表明迫切需要有效解决2型糖尿病患者的依从性。