OBJECTIVE The 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-1 RA) or dipeptidyl peptidase 4 (DPP-4) inhibitor 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-1 RA (n = 221) or a DPP-4 (n = 652) experienced smaller reductions in HbA_1c (GLP-1 RA: −0.52% [−6 mmol/mol], DPP-4: −0.51% [−6 mmol/mol])than reported in RCTs (−1.30% [−14 mmol/mol] from seven GLP-1 RA RCTs, n = 2,600; −0.68% [−8 mmol/mol] from four DPP-4 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-1 RA [−12 mmol/mol], −0.69% DPP-4 [−8 mmol/mol]) were within the RCTs’ reported range (GLP-1 RA: −0.84% to −1.60% [−9 to −18 mmol/mol], DPP-4: −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] GLP-1 RA; 0.18% [3 mmol/mol] DPP-4).

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。

研究设计和方法这项混合方法的准实验研究使用回顾性声明（Optum / Humedica）比较了开始使用胰高血糖素样肽1受体激动剂（GLP-1）12个月后的RW型2型糖尿病患者HbA _1c的变化。RA）或二肽基肽酶4（DPP-4）抑制剂，已发表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-1 RA（n = 221）或DPP-4（n = 652）的RW患者的HbA _1c降低幅度较小（GLP-1 RA：−0.52％[−6 mmol / mol]，DPP-4 ：-0.51％[−6 mmol / mol]），比RCTs报告的结果（来自七个GLP-1 RA RCT的-1.30％[−14 mmol / mol]，n = 2,600； -0.68％[−8 mmol / mol]来自7个GLP-1 RA RCTs ）四个DPP-4 RCT，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-1 RA [−12 mmol / mol]，− 0.69％DPP-4 [−8 mmol / mol]）在RCT报告的范围内（GLP-1 RA：−0.84 ％至-1.60％[-9至-18mmol / mol]，DPP-4：-0.47％至-0.90％[-5至-10mmol / mol]。药物依从性差约占RW与预期RCT结果之间的差距的四分之三（差距= 0.51％[6 mmol / mol] GLP-1 RA； 0.18％[3 mmol / mol] DPP-4）。

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。