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1 Supplementary Online Content Vashisht R, Jung K, Schuler A, et al. Association of hemoglobin A 1c 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. JAMA Netw Open. 2018;1(4):e doi: /jamanetworkopen eappendix. OMOP Common Data Model etable 1. Concept IDs Utilized for Outcome MI, KD, ED and KD etable 2. Concepts Used as Negative Controls for P Value Calibration etable 3. Number of Patients Before and After Matching for Each Drug Comparison and Outcome HbA 1c etable 4. Number of Patients Before and After Matching for Each Drug Comparison and Outcome Myocardial Infarction etable 5. Number of Patients Before and After Matching for Each Drug Comparison and Outcome Kidney Disorders etable 6. Number of Patients Before and After Matching for Each Drug Comparison and Outcome Eye Disorders etable 7. Information Before and After Matching for Each Drug Comparison Based on the Data From Truven MarketScan CCAE etable 8. Information Before and After Matching for Each Drug Comparison Based on the Data From Columbia University etable 9. Information Before and After Matching for Each Drug Comparison Based on the Data From IQVIA Disease Analyzer France etable 10. Information Before and After Matching for Each Drug Comparison Based on the Data From Truven MarketScan MDCR etable 11. Information Before and After Matching for Each Drug Comparison Based on the Data From Mount Sinai etable 12. Information Before and After Matching for Each Drug Comparison Based on the Data From Optum Clinformatics Data Mart etable 13. Information Before and After Matching for Each Drug Comparison Based on the Data From Ajou University, South Korea etable 14. Information Before and After Matching for Each Drug Comparison Based on the Data From Stanford University etable 15. Mean, Median and Standard Deviation of HbA 1c Values for the Comparison of Sulfonylureas vs DPP4 Inhibitors Across Eight Study Sites etable 16. Mean, Median and Standard Deviation of HbA 1c Values for the Comparison of Sulfonylureas vs Thiazolidinediones Across Eight Study Sites etable 17. Mean, Median and Standard Deviation of HbA 1c Values for the Comparison of DPP4 Inhibitors vs Thiazolidinediones Across Eight Study Sites
2 etable 18. Number of Patients, Hazard Ratio, Confidence Intervals (CI), P Values and Calibrated P Values for Each Drug Comparison and Each Outcome Based on Analysis Across All Eight Study Sites efigure 1. Cohort Construction efigure 2. Comparative Effectiveness of Sulfonylureas vs Thiazolidinediones efigure 3. Comparative Effectiveness of DPP-4 Inhibitors vs Thiazolidinediones This supplementary material has been provided by the authors to give readers additional information about their work.
3 eappendix 1. OMOP Common Data Model The OMOP Common Data Model (CDM) allows for the systematic analysis of disparate observational databases. The core idea is to transform data contained within different databases into a common format (data model) as well as a common representation (terminologies, vocabularies, coding schemes), and then perform systematic analyses using a library of standard analytic routines based on the common format. CDM is designed to store observational data to allow for research, under the following principles: Suitability for purpose: The CDM aims at providing data organized in a way optimal for analysis, rather than for the purpose of operational needs of health care providers or payers. Data protection: All data that might jeopardize the identity and protection of patients, such as names, precise birthdays etc. are limited. Exceptions are possible where the research expressly requires more detailed information, such as precise birth dates for the study of infants. Design of domains: The domains are modeled in a person-centric relational data model, where for each record the identity of the person and a date is captured as a minimum. Rationale for domains: Domains are identified and separately defined in an Entity-relationship model if they have an analysis use case and the domain has specific attributes that are not otherwise applicable. All other data can be preserved as an observation in an entity-attribute-value structure. Standardized Vocabularies: To standardize the content of those records, the CDM relies on the Standardized Vocabularies containing all necessary and appropriate corresponding standard healthcare concepts. Reuse of existing vocabularies: If possible, these concepts are leveraged from national or industry standardization or vocabulary definition organizations or initiatives, such as the National Library of Medicine, the Department of Veterans' Affairs, the Center of Disease Control and Prevention, etc. Maintaining source codes: Even though all codes are mapped to the Standardized Vocabularies, the model also stores the original source code to ensure no information is lost. Technology neutrality: The CDM does not require a specific technology. It can be realized in any relational database, such as Oracle, SQL Server etc., or as SAS analytical datasets. Scalability: The CDM is optimized for data processing and computational analysis to accommodate data sources that vary in size, including databases with up to hundreds of millions of persons and billions of clinical observations. Backwards compatibility: All changes from previous CDMs are clearly delineated. Older versions of the CDM can be easily created from this CDMv5, and no information is lost that was present previously.
4 Detailed discussion related to the above mentioned design principles of OMOP-CDM data model can be explored in detail at
5 etable 1. Concept IDs Utilized for Outcome MI, KD, ED and KD Drug Comparison: Sulfonylureas vs DPP4 inhibitors Outcome: Myocardial Infarction Concept Identifier Concept Name Number of Patients Sulfonylureas Acute myocardial infarction Acute myocardial infarction of inferior 1 wall DPP4 inhibitors Acute subendocardial infarction Acute myocardial infarction 1 Comparison: Sulfonylureas vs DPP4 inhibitors Outcome: Kidney Disorders Drug Concept Identifier Concept Name Sulfonylureas Renal disorder due to type 2 diabetes 14 mellitus Diabetic renal disease Acute renal failure syndrome Kidney stone Chronic renal failure Hypertensive renal disease with renal 3 failure Chronic kidney disease stage Pyelonephritis Hypertensive heart and renal disease with 2 (congestive) heart failure Chronic kidney disease stage Cystic disease of kidney Nephritis Renal agenesis and dysgenesis Acquired renal cystic disease Primary malignant neoplasm of kidney Hydronephrosis 1 DPP4 inhibitors Acute renal failure syndrome Diabetic renal disease Cystic disease of kidney Kidney stone Renal disorder due to type 2 diabetes 2 mellitus Acute tubular necrosis Renal failure syndrome Nephritis Acquired renal cystic disease 1 Number of Patients
6 Drug Chronic renal failure Hydronephrosis Hypertensive renal disease with renal 1 failure Chronic kidney disease stage 3 1 Comparison: Sulfonylureas vs DPP4 inhibitors Outcome: Eye Disorders Concept Concept Name Identifier Sulfonylureas Nuclear senile cataract Nonproliferative diabetic retinopathy Borderline glaucoma Cataract 1 Number of Patients Moderate nonproliferative diabetic retinopathy Mild non-proliferative diabetic retinopathy Angle-closure glaucoma - borderline Capsular fibrosis Glaucoma 1 DPP4 inhibitors Nuclear senile cataract related cataract Central serous chorioretinopathy Cataract Nonproliferative diabetic retinopathy Primary open angle glaucoma Borderline glaucoma 1 Comparison: Sulfonylureas vs Thiazolidinediones Outcome: Myocardial Infarction Drug Concept Identifier Concept Name Number of Patients Sulfonylureas Acute myocardial infarction of inferior wall 1 Thiazolidinediones Acute subendocardial infarction 2 Comparison: Sulfonylureas vs Thiazolidinediones Outcome: Kidney disorders Drug Concept Identifier Concept Name Sulfonylureas Renal disorder due to type 2 diabetes 9 mellitus Acute renal failure syndrome Diabetic renal disease Chronic kidney disease stage Hypertensive renal disease with renal 5 failure Chronic renal failure 3 Number of Patients
7 Nephritis Kidney stone Chronic kidney disease stage Nephrotic syndrome Pyelonephritis Hydronephrosis Acute tubular necrosis 1 Thiazolidinediones Diabetic renal disease Renal disorder due to type 2 diabetes 5 mellitus Acute renal failure syndrome Kidney stone Hypertensive renal disease with renal 2 failure Chronic kidney disease stage Chronic kidney disease stage Cystic disease of kidney End stage renal disease Chronic renal failure 1 Comparison: Sulfonylureas vs Thiazolidinediones Outcome: Eye disorder Drug Concept Identifier Concept Name Sulfonylureas Nuclear senile cataract Cataract Diabetic macular edema Primary open angle glaucoma Glaucoma Severe nonproliferative diabetic 1 retinopathy Nonproliferative diabetic retinopathy Hypertensive retinopathy Proliferative diabetic retinopathy Glaucoma associated with vascular 1 disorder Borderline glaucoma 1 Thiazolidinediones Nuclear senile cataract Cataract Mild non-proliferative diabetic retinopathy Glaucoma related cataract Primary open angle glaucoma Open angle with borderline intraocular 1 pressure Borderline glaucoma 1 Number of Patients
8 Comparison: DPP4 inhibitors vs Thiazolidinediones Outcome: Myocardial Infarction Drug Concept Identifier Concept Name Number of Patients DPP4 inhibitors Acute subendocardial infarction 1 Thiazolidinediones NA NA NA Comparison: DPP4 inhibitors vs Thiazolidinediones Outcome: Kidney disorders Drug Concept Identifier Concept Name DPP4 inhibitors Acute renal failure syndrome Renal disorder due to type 2 diabetes 4 mellitus Diabetic renal disease Acquired renal cystic disease Chronic kidney disease stage Acute tubular necrosis Renal failure syndrome Cystic disease of kidney Nephritis Chronic renal failure Kidney stone Hypertensive renal disease with renal 1 failure Thiazolidinediones Acute renal failure syndrome Diabetic renal disease Renal disorder due to type 2 diabetes 4 mellitus Chronic renal failure Chronic kidney disease stage Cystic disease of kidney Kidney stone 1 Drug Number of Patients Hypertensive renal disease with renal 1 failure Chronic kidney disease stage Anemia of chronic renal failure 1 Comparison: DPP4 inhibitors vs Thiazolidinediones Outcome: Eye disorders Concept Identifier Concept Name DPP4 inhibitors Nuclear senile cataract Nonproliferative diabetic retinopathy related cataract Glaucoma Borderline glaucoma 1 Number of Patients
9 Thiazolidinediones Nuclear senile cataract Cataract Glaucoma Mild non-proliferative diabetic retinopathy related cataract Open angle with borderline intraocular 1 pressure Borderline glaucoma 1 SNOMED codes for secondary outcomes were obtained by searching for terms in the CDM s vocabulary tables. To build the set of SNOMED codes eye-related disorders and kidney related disorders, we started with a keyword based search of SNOMED labels, and included the matching concepts as well as their subclasses in the OHDSI Standard Vocaulary ( Vocabularies). This process generates a seemingly large list of concepts that correspond to the outcome of interest. In practice, not all the child codes are instantiated in the data. We show the frequency at which specific codes were actually seen in the cohorts analyzed at Stanford to illustrate which codes are actually instantiated in the data. Concepts utilized for identifying patients with myocardial Infarction, kidney disorders and eye disorders are shown in the table below. Each concept is ordered based on the total number of patients identified by the concept.
10 etable 2. Concepts Used As Negative Controls for P Value Calibration Concept Identifier Concept Name Acute conjunctivitis Alcohol abuse Allergic rhinitis Anxiety disorder Bipolar disorder Carpal tunnel syndrome Chronic obstructive lung disease Chronic sinusitis Conduct disorder Contact dermatitis Contusion of knee Corneal opacity Corns and callus Dental caries Diffuse spasm of esophagus Disease caused by parasite Disorder of ear Disorder of oral soft tissues Disorder of pharynx Disorder of sebaceous gland Herpes zoster without complication Human papilloma virus infection Hypothyroidism Impacted cerumen Ingrowing nail Insomnia Internal hemorrhoids without complication Lumbar sprain Lupus erythematosus Mood disorder Obsessive-compulsive disorder Otalgia Otitis media Plantar fasciitis Presbyopia Psychotic disorder Sarcoidosis
11 Schizoaffective schizophrenia Schizophrenia Sciatica Solitary sacroiliitis Tinea pedis Vitamin D deficiency
12 etable 3. Number of Patients Before and After Matching for Each Drug Comparison and Outcome HbA 1c Dataset Sulfonylureas (T) vs DPP4 inhibitors (C) Sulfonylureas (T) vs Thiazolidinediones (C) DPP4 inhibitors (T) vs Thiazolidinediones (C) T C T C T C T C T C T C Truven MarketScan CCAE Columbia University IQVIA Disease Analyser France Truven MarketScan MDCR Mt. Sinai Optum Clinformatics Data Mart Ajou University, South Korea Stanford University
13 etable 4. Number of Patients Before and After Matching for Each Drug Comparison and Outcome Myocardial Infarction Dataset Sulfonylureas (T) vs DPP4 inhibitors (C) Sulfonylureas (T) vs Thiazolidinediones (C) DPP4 inhibitors (T) vs Thiazolidinediones (C) T C T C T C T C T C T C Truven MarketScan CCAE Columbia University IQVIA Disease Analyser France Truven MarketScan MDCR Mt. Sinai Optum Clinformatics Data Mart Ajou University, South Korea Stanford University
14 etable 5. Number of Patients Before and After Matching for Each Drug Comparison and Outcome Kidney Disorders Dataset Sulfonylureas (T) vs DPP4 inhibitors (C) Sulfonylureas (T) vs Thiazolidinediones (C) DPP4 inhibitors (T) vs Thiazolidinediones (C) T C T C T C T C T C T C Truven MarketScan CCAE Columbia University IQVIA Disease Analyser France Truven MarketScan MDCR Mt. Sinai Optum Clinformatics Data Mart Ajou University, South Korea Stanford University
15 etable 6. Number of Patients Before and After Matching for Each Drug Comparison and Outcome Eye Disorders Dataset Sulfonylureas (T) vs DPP4 inhibitors (C) Sulfonylureas (T) vs Thiazolidinediones (C) DPP4 inhibitors (T) vs Thiazolidinediones (C) T C T C T C T C T C T C Truven MarketScan CCAE Columbia University IQVIA Disease Analyser France Truven MarketScan MDCR Mt. Sinai Optum Clinformatics Data Mart Ajou University, South Korea Stanford University
16 etable 7. Information Before and After Matching for Each Drug Comparison Based on the Data From Truven MarketScan CCAE Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: HbA1c group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Myocardial Infarction group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Kidney Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA
17 Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Eye Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: HbA1c group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Myocardial Infarction group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA
18 Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Kidney Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Eye Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: HbA1c group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors
19 Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Myocardial Infarction group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Kidney Disorders group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Eye Disorders group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors
20
21 etable 8. Information Before and After Matching for Each Drug Comparison Based on the Data From Columbia University Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: HbA1c group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA 1 Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Myocardial Infarction group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA 1 Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Kidney Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA
22 NA 1 Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Eye Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA 1 Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: HbA1c group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA NA 3 NA
23 NA 1 NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Myocardial Infarction group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA 3 NA NA NA NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Kidney Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA 4 NA NA NA NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Eye Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones
24 NA NA NA NA NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: HbA1c group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors NA 2 NA NA NA NA 1 NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Myocardial Infarction group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors NA 2 NA
25 NA 1 NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Kidney Disorders group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors NA 2 NA NA 1 NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Eye Disorders group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors NA 2 NA NA
26 NA 1 NA
27 etable 9. Information Before and After Matching for Each Drug Comparison Based on the Data From IQVIA Disease Analyzer France Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: HbA1c group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Myocardial Infarction group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Kidney Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA
28 Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Eye Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: HbA1c group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA 1 NA NA NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Myocardial Infarction
29 group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA 1 NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Kidney Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA 1 NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Eye Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA 1 NA
30 Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: HbA1c group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors NA 1 NA NA NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Myocardial Infarction group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors NA 1 NA NA
31 Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Kidney Disorders group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors NA 1 NA NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Eye Disorders group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors NA 1 NA NA
32 etable 10. Information Before and After Matching for Each Drug Comparison Based on the Data From Truven MarketScan MDCR Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: HbA1c group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Myocardial Infarction group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Kidney Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA NA Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Eye Disorders
33 group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: HbA1c group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA 1 NA NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Myocardial Infarction group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA 1 NA NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Kidney Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA 1 NA 1
34 NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Eye Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA 1 NA NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: HbA1c DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones group inhibitors NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Myocardial Infarction DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones group inhibitors NA
35 Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Kidney Disorders DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones group inhibitors NA NA 5 Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Eye Disorders DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones group inhibitors NA NA
36 etable 11. Information Before and After Matching for Each Drug Comparison Based on the Data From Mount Sinai Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: HbA1c group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Myocardial Infarction group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Kidney Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA
37 Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Eye Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: HbA1c group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA
38 NA 2 NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Myocardial Infarction group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA 1 NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Kidney Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA NA 2 NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Eye Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones
39 NA 2 NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: HbA1c DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones group inhibitors NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Myocardial Infarction DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones group inhibitors
40 Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Kidney Disorders DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones group inhibitors Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Eye Disorders DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones group inhibitors
41 etable 12. Information Before and After Matching for Each Drug Comparison Based on the Data From Optum Clinformatics Data Mart Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: HbA1c group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors 5-9 NA 1 NA NA Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Myocardial Infarction group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors 5-9 NA 1 NA Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Kidney Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors
42 5-9 NA 1 NA Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Eye Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors 5-9 NA 1 NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: HbA1c group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones 5-9 NA 1 NA NA
43 Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Myocardial Infarction group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones 5-9 NA 1 NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Kidney Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones 5-9 NA 1 NA
44 Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Eye Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones 5-9 NA 1 NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: HbA1c DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones group inhibitors NA NA NA
45 Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Myocardial Infarction DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones group inhibitors NA NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Kidney Disorders DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones group inhibitors NA NA
46 Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Eye Disorders DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones group inhibitors NA NA
47 etable 13. Information Before and After Matching for Each Drug Comparison Based on the Data From Ajou University, South Korea Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: HbA1c group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Myocardial Infarction group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Kidney Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors
48 Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Eye Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: HbA1c group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA NA NA
49 NA 2 NA NA NA NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Myocardial Infarction group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA NA NA NA 2 NA NA NA NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Kidney Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA NA NA 2 NA NA 1 NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Eye Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA 1
50 NA NA 2 NA NA NA NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: HbA1c group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors NA 1 NA NA NA NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Myocardial Infarction group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors
51 NA 1 NA NA 1 NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Kidney Disorders group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors NA 1 NA NA 1 NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Eye Disorders group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors
52 NA NA NA NA NA NA
53 etable 14. Information Before and After Matching for Each Drug Comparison Based on the Data From Stanford University Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: HbA1c group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA NA NA Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Myocardial Infarction group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA NA NA 1 Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Kidney Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA
54 NA NA 1 Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Eye Disorders group Sulfonylureas DPP4 inhibitors Sulfonylureas DPP4 inhibitors NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: HbA1c group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA NA NA NA NA NA NA 2 NA
55 NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Myocardial Infarction group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA NA NA NA 1 NA NA NA 3 NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Kidney Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA 1 NA NA NA NA NA NA 1 NA NA 1
56 Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Eye Disorders group Sulfonylureas Thiazolidinediones Sulfonylureas Thiazolidinediones NA NA NA NA NA NA NA NA 3 NA NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: HbA1c group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors NA NA NA NA 1 NA NA NA 4 NA NA NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Myocardial Infarction group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors NA 1 NA NA 1 NA
57 NA 4 NA NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Kidney Disorders group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors NA 1 NA NA 1 NA NA 5 NA NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Eye Disorders group DPP4 inhibitors Thiazolidinediones DPP4 Thiazolidinediones inhibitors NA 1 NA NA 1 NA NA 4 NA
58 NA NA NA
59 etable 15. Mean, Median and Standard Deviation of HbA 1c Values for the Comparison of Sulfonylureas vs DPP4 Inhibitors Across Eight Study Sites Truven MarketScan CCAE Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas 9.00 (1.85) 9.01 (1.73) 7.89 (1.87) 7.70 (1.92) DPP4 inhibitors 8.67 (1.70) 8.92 (1.68) 7.58 (1.99) 7.61 (1.98) Columbia University Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas (2.33) (2.38) 8.50 (1.95) 8.02 (1.85) DPP4 inhibitors 8.52 (1.27) 8.57 (1.39) 7.70 (1.77) 7.70 (1.79) IQVIA Disease Analyser France Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas (39.2) 8.44 (1.41) 7.51 (1.86) 7.87 (5.4) DPP4 inhibitors 8.52 (2.3) 8.53 (1.28) 7.81 (5.08) 7.50 (1.68) Truven MarketScan MDCR Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas 8.46 (1.48) 8.40 (1.43) 7.42 (1.47) 7.29 (1.81) DPP4 inhibitors 8.31 (1.29) 8.45 (1.37) 7.48 (4.43) 7.48 (4.44) Mt. Sinai Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas 9.20 (1.76) 9.03 (1.61) 7.89 (1.90) 7.71 (1.78) DPP4 inhibitors 8.66 (1.45) 8.67 (1.35) 7.45 (1.48) 7.45 (1.48) Optum Clinformatics Data Mart Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas 8.77 (4.88) 8.94 (3.82) 7.89 (5.51) 7.87 (6.18) DPP4 inhibitors 8.48 (3.25) 8.85 (3.26) 7.93 (5.9) 7.93 (5.84) Ajou University, South Korea Drug Before Index date After Index date
60 AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas 7.63 (1.28) 8.25 (1.55) 7.68 (1.47) 7.56 (1.37) DPP4 inhibitors 7.89 (1.57) 7.99 (1.37) 7.47 (1.19) 7.45 (1.18) Stanford University Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas 9.22 (1.71) 8.74 (1.59) 7.95 (1.67) 7.89 (1.52) DPP4 inhibitors 8.85 (1.52) 8.69 (1.76) 7.50 (1.34) 7.50 (1.33)
61 etable 16. Mean, Median and Standard Deviation of HbA 1c Values for the Comparison of Sulfonylureas vs Thiazolidinediones Across Eight Study Sites Truven MarketScan CCAE Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas 8.96 (1.84) 9.09 (1.73) 7.85 (1.91) 7.82 (1.86) Thiazolidinediones 8.97 (1.74) 9.13 (1.73) 7.76 (1.82) 7.76 (1.83) Columbia University Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas (2.3) (2.51) 8.45 (1.92) 8.50 (1.96) Thiazolidinediones 9.94 (2.37) 9.23 (1.62) 8.36 (2.05) 8.36 (2.05) IQVIA Disease Analyser France Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas 8.82 (3.14) 8.65 (1.44) 7.71 (11.49) 7.62 (2.33) Thiazolidinediones (38.97) 8.77 (1.28) 7.52 (2.6) 7.77 (13.31) Truven MarketScan MDCR Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas 8.48 (1.47) 8.61 (1.66) 7.40 (1.48) 7.33 (1.32) Thiazolidinediones 8.54 (1.29) 8.55 (1.3) 7.53 (3.81) 7.54 (3.84) Mt. Sinai Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas 9.10 (1.69) 9.09 (1.68) 7.80 (1.81) 7.80 (1.69) Thiazolidinediones 8.97 (1.64) 8.90 (1.58) 7.63 (1.82) 7.63 (1.83) Optum Clinformatics Data Mart Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas 8.83 (17.63) 9.12 (3.22) 7.90 (5.58) 7.84 (4.21) Thiazolidinediones 8.83 (3.34) 9.09 (4.00) 7.72 (4.00) 7.73 (4.03) Ajou University, South Korea Drug Before Index date After Index date
62 AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas 7.95 (1.63) 8.27 (1.65) 7.71 (1.47) 7.69 (1.41) Thiazolidinediones 7.97 (1.46) 8.10 (1.27) 7.87 (1.49) 7.79 (1.45) Stanford University Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) Sulfonylureas 9.07 (1.67) 9.73 (2.27) 7.96 (1.63) 8.00 (1.49) Thiazolidinediones 9.03 (2.08) 9.25 (2.29) 7.66 (1.72) 7.66 (1.72)
63 etable 17. Mean, Median and Standard Deviation of HbA 1c Values for the Comparison of DPP4 Inhibitors vs Thiazolidinediones Across Eight Study Sites Truven MarketScan CCAE Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) DPP4 inhibitors 8.71 (1.7) 9.03 (1.69) 7.64 (2.05) 7.72 (2.01) Thiazolidinediones 9.04 (1.75) 9.18 (1.76) 7.86 (1.83) 7.73 (1.91) Columbia University Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) DPP4 inhibitors 8.60 (1.36) 8.42 (1.35) 8.02 (1.77) 8.00 (1.77) Thiazolidinediones 9.94 (2.35) 9.08 (1.65) 8.61 (2.07) 8.55 (2.13) IQVIA Disease Analyser France Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) DPP4 inhibitors 8.51 (2.24) 8.61 (1.60) 7.81 (5.24) 7.85 (5.18) Thiazolidinediones 8.78 (2.9) 8.69 (1.39) 7.77 (11.7) 8.00 (16.00) Truven MarketScan MDCR Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) DPP4 inhibitors 8.36 (1.32) 8.57 (1.35) 7.45 (1.53) 7.48 (1.45) Thiazolidinediones 8.44 (1.25) 8.60 (1.40) 7.51 (1.36) 7.39 (1.37) Mt. Sinai Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) DPP4 inhibitors 8.59 (1.33) 8.93 (1.63) 7.60 (1.60) 7.61 (1.69) Thiazolidinediones 9.22 (1.70) 9.10 (1.66) 8.02 (2.01) 7.82 (1.87) Optum Clinformatics Data Mart Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) DPP4 inhibitors 8.65 (19.34) 9.06 (3.45) 7.96 (5.59) 7.98 (4.76) Thiazolidinediones 8.91 (3.56) 9.16 (4.88) 7.77 (3.65) 7.81 (4.40) Ajou University, South Korea Drug Before Index date After Index date
64 AVG (SD) AVG (SD) AVG (SD) AVG (SD) DPP4 inhibitors 7.69 (1.33) 7.93 (1.33) 7.56 (1.30) 7.59 (1.27) Thiazolidinediones 8.07 (1.57) 8.24 (1.47) 7.86 (1.49) 7.83 (1.46) Stanford University Drug Before Index date After Index date AVG (SD) AVG (SD) AVG (SD) AVG (SD) DPP4 inhibitors 8.69 (1.40) 8.98 (1.80) 7.75 (1.31) 7.73 (1.29) Thiazolidinediones 8.91 (1.67) 9.05 (1.74) 7.85 (1.73) 7.90 (1.73)
65 etable 18. Number of Patients, Hazard Ratio, Confidence Intervals (CI), P Values and Calibrated P Values for Each Drug Comparison and Each Outcome Based on Analysis Across All Eight Study Sites. Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: HbA1c Study Site N Hazard Ratio 95% CI Lower bound 95% CI Upper bound P-Value Calibrated P- Value Truven Marketscan CCAE Columbia University IQVIA Disease Analyser France Truven Marketscan MDCR Mt Sinai Optum Clinformatics Data Mart Ajou University Stanford University Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Myocardial Infarction Study Site N Hazard Ratio 95% CI Lower bound 95% CI Upper bound P-Value Calibrated P- Value Truven Marketscan CCAE Columbia University IQVIA Disease Analyser France Truven Marketscan MDCR Mt Sinai Optum Clinformatics Data Mart Ajou University Stanford University Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Kidney Disorders
66 Study Site N Hazard Ratio 95% CI Lower bound 95% CI Upper bound P-Value Calibrated P- Value Truven Marketscan CCAE Columbia University IQVIA Disease Analyser France Truven Marketscan MDCR Mt Sinai Optum Clinformatics Data Mart Ajou University Stanford University Comparison: Sulfonylureas vs DPP4 inhibitors - Outcome: Eye Disorders Study Site N Hazard Ratio 95% CI Lower bound 95% CI Upper bound P-Value Calibrated P- Value Truven Marketscan CCAE Columbia University IQVIA Disease Analyser France Truven Marketscan MDCR Mt Sinai Optum Clinformatics Data Mart Ajou University Stanford University Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: HbA1c Study Site N Hazard Ratio 95% CI Lower bound 95% CI Upper bound P-Value Calibrated P- Value
67 Truven Marketscan CCAE Columbia University IQVIA Disease Analyser France Truven Marketscan MDCR Mt Sinai Optum Clinformatics Data Mart Ajou University NA Stanford University Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Myocardial Infarction Study Site N Hazard Ratio 95% CI Lower bound 95% CI Upper bound P-Value Calibrated P- Value Truven Marketscan CCAE Columbia University IQVIA Disease Analyser France Truven Marketscan MDCR Mt Sinai Optum Clinformatics Data Mart Ajou University 181 NA NA NA NA NA Stanford University NA 1.61 NA NA Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Kidney Disorders Study Site N Hazard Ratio 95% CI Lower bound 95% CI Upper bound P-Value Calibrated P- Value Truven Marketscan CCAE Columbia University IQVIA Disease Analyser France Truven Marketscan MDCR
68 Mt Sinai Optum Clinformatics Data Mart Ajou University NA Stanford University Comparison: Sulfonylureas vs Thiazolidinediones - Outcome: Eye Disorders Study Site N Hazard Ratio 95% CI Lower bound 95% CI Upper bound P-Value Calibrated P- Value Truven Marketscan CCAE Columbia University IQVIA Disease Analyser France Truven Marketscan MDCR Mt Sinai Optum Clinformatics Data Mart Ajou University NA Stanford University Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: HbA1c Study Site N Hazard Ratio 95% CI Lower bound 95% CI Upper bound P-Value Calibrated P- Value Truven Marketscan CCAE Columbia University IQVIA Disease Analyser France Truven Marketscan MDCR Mt Sinai Optum Clinformatics Data Mart Ajou University NA Stanford University
69 Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Myocardial Infarction 95% CI 95% CI Lower Upper bound bound Study Site N Hazard Ratio P-Value Calibrated P- Value Truven Marketscan CCAE Columbia University IQVIA Disease Analyser France Truven Marketscan MDCR Mt Sinai Optum Clinformatics Data Mart Ajou University 211 NA NA NA NA NA Stanford University 175 NA NA NA NA NA Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Kidney Disorders Study Site N Hazard Ratio 95% CI Lower bound 95% CI Upper bound P-Value Calibrated P- Value Truven Marketscan CCAE Columbia University IQVIA Disease Analyser France Truven Marketscan MDCR Mt Sinai Optum Clinformatics Data Mart Ajou University NA Stanford University Comparison: DPP4 inhibitors vs Thiazolidinediones - Outcome: Eye Disorders Study Site N Hazard Ratio 95% CI Lower bound 95% CI Upper bound P-Value Calibrated P- Value
70 Truven Marketscan CCAE Columbia University IQVIA Disease Analyser France Truven Marketscan MDCR Mt Sinai Optum Clinformatics Data Mart Ajou University NA Stanford University
71 efigure 1. Cohort Construction Steps involved in cohort construction and censoring for the time-to-event analysis, using the Sulfonylureas cohort as an example. A patient is selected based on following conditions. Prescription of Second-line drug (Sulfonylureas, DPP4 Inhibitors, or Thiazolidinediones). The date of prescription is considered as the index date relative to which patient is filtered. Patient should have a prescription of Metformin at least 90 days prior to index date. Patient should have a mention of T2D related codes before index date and no mention of type 1 diabetes codes before the index date. The ICD9-CM or ICD10- CM codes were mapped to their corresponding SNOMED codes to identify patients in the OMOP-CDM schema. No prescription of any other T2D related drug among alpha-glucose inhibitors, DPP4 inhibitors, thiazolidinediones, SGLT2 inhibitors, glucagones and meglitinide before the index date including Insulin. Reported HbA 1c value after the prescription of sulfonylurea. Can have reported incidence of myocardial infarction, kidney disorders and eye disorders. Patient is right censored depending on the outcome of interest under investigation. The patient is right censored if prescription of any drug among alpha-glucose inhibitors, DPP4 inhibitors, thiazolidinediones, SGLT2 inhibitors, glucagon-like peptide receptor agonists, or meglitinide is observed after the prescription of sulfonylurea. In case of absence of event the complete length of patient's medical record is used as the observational window. efigure 1 represents the steps involved in the cohort construction for Sulfonylureas cohort, as an example.
72 efigure 2. Comparative Effectiveness of Sulfonylureas vs Thiazolidinediones A) Flowchart of matched cohort construction based on the data from Optum, B) covariate balance as standardized mean difference before and after matching based on the data from Optum C) Kaplan-Meier curves for the reduction of HbA 1c <= 7% based on the data from Optum D) Empirical calibration plots based on the data from Optum where estimates below the dashed line in gray area have p < 0.05 using traditional p-value calculation. Estimates in the orange area have p < 0.05 using calibrated p-value calculation. Yellow dots represents outcome and blue dots represent negative controls E) Hazard ratio (HR) of observing a reduction in HbA 1c <= 7% after treatment with either sulfonylurea or thiazolidinediones across multiple healthcare systems and consensus effect based on meta-analysis. An HR > 1 mean sulfonylureas are associated with higher hazaed of reducing HbA 1c compared to thiazolidinediones. Hazard ratio of observing an event related to F) myocardial infarction G) kidney disorder and H) eye disorder across multiple healthcare systems along with meta-analysis. An HR < 1 means sulfonylureas are associated with a lower hazard of the outcome related to myocardial infarction, kidney and eye disorders. I 2 values for each meta-analysis in E-H are shown in the bottom left of each outcome box.
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