Association of Hemoglobin A1c Levels With Use of Sulfonylureas, Dipeptidyl Peptidase 4 Inhibitors, and Thiazolidinediones in Patients With Type 2 Diabetes Treated With Metformin: Analysis From the Observational Health Data Sciences and Informatics Initiative

• Published in: JAMA network open 2018-08, Vol.1 (4), p.e181755
• Main Authors: Vashisht, Rohit, Jung, Kenneth, Schuler, Alejandro, Banda, Juan M, Park, Rae Woong, Jin, Sanghyung, Li, Li, Dudley, Joel T, Johnson, Kipp W, Shervey, Mark M, Xu, Hua, Wu, Yonghui, Natrajan, Karthik, Hripcsak, George, Jin, Peng, Van Zandt, Mui, Reckard, Anthony, Reich, Christian G, Weaver, James, Schuemie, Martijn J, Ryan, Patrick B, Callahan, Alison, Shah, Nigam H
• Format: Article
• Language: English
• Subjects: Antidiabetics; Cohort Studies; Data science; Diabetes; Diabetes and Endocrinology; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Dipeptidyl-Peptidase IV Inhibitors - adverse effects; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Female; Glycated Hemoglobin A - analysis; Heart attacks; Hemoglobin; Humans; Hypoglycemic Agents - therapeutic use; Informatics; Male; Metformin - therapeutic use; Online Only; Original Investigation; Sulfonylurea Compounds - adverse effects; Sulfonylurea Compounds - therapeutic use; Thiazolidinediones - adverse effects; Thiazolidinediones - therapeutic use
• ISSN: 2574-3805
• DOI: 10.1001/jamanetworkopen.2018.1755

Consensus around an efficient second-line treatment option for type 2 diabetes (T2D) remains ambiguous. The availability of electronic medical records and insurance claims data, which capture routine medical practice, accessed via the Observational Health Data Sciences and Informatics network presents an opportunity to generate evidence for the effectiveness of second-line treatments. To identify which drug classes among sulfonylureas, dipeptidyl peptidase 4 (DPP-4) inhibitors, and thiazolidinediones are associated with reduced hemoglobin A1c (HbA1c) levels and lower risk of myocardial infarction, kidney disorders, and eye disorders in patients with T2D treated with metformin as a first-line therapy. Three retrospective, propensity-matched, new-user cohort studies with replication across 8 sites were performed from 1975 to 2017. Medical data of 246 558 805 patients from multiple countries from the Observational Health Data Sciences and Informatics (OHDSI) initiative were included and medical data sets were transformed into a unified common data model, with analysis done using open-source analytical tools. Participants included patients with T2D receiving metformin with at least 1 prior HbA1c laboratory test who were then prescribed either sulfonylureas, DPP-4 inhibitors, or thiazolidinediones. Data analysis was conducted from 2015 to 2018. Treatment with sulfonylureas, DPP-4 inhibitors, or thiazolidinediones starting at least 90 days after the initial prescription of metformin. The primary outcome is the first observation of the reduction of HbA1c level to 7% of total hemoglobin or less after prescription of a second-line drug. Secondary outcomes are myocardial infarction, kidney disorder, and eye disorder after prescription of a second-line drug. A total of 246 558 805 patients (126 977 785 women [51.5%]) were analyzed. Effectiveness of sulfonylureas, DPP-4 inhibitors, and thiazolidinediones prescribed after metformin to lower HbA1c level to 7% or less of total hemoglobin remained indistinguishable in patients with T2D. Patients treated with sulfonylureas compared with DPP-4 inhibitors had a small increased consensus hazard ratio of myocardial infarction (1.12; 95% CI, 1.02-1.24) and eye disorders (1.15; 95% CI, 1.11-1.19) in the meta-analysis. Hazard of observing kidney disorders after treatment with sulfonylureas, DPP-4 inhibitors, or thiazolidinediones was equally likely. The examined drug classes did not differ in lowering HbA1c and in hazards of kidn