Observational studyJAMA network open2018
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.
Observational study in JAMA network open, 2018. The graph read 2 numbers from its abstract, feeding 2 cells of the map: it . It also reports an association that does not count as treatment evidence, such as HR 1.12 (1.02 to 1.24) for cardiovascular events. Cited by 35 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
This meta-analysis indicated that there was not a significant difference between sulfonylureas vs DPP-4 inhibitors in the reduction of HbA 1c levels to 7% of total hemoglobin or less (consensus HR, 0.99; 95% CI, 0.89-1.10) ( Table 2 and Figure 4 A).
Read, but not usablea number the graph found but could not read as for or against
For the secondary outcomes, the comparison of sulfonylureas with DPP-4 inhibitors, where study heterogeneity was low, showed a small increased hazard of myocardial infarction (consensus HR, 1.12; 95% CI, 1.02-1.24) and eye disorders (consensus HR, 1.15; 95% CI, 1.11-1.19) in the meta-analysis, although the recalibrated P values (eTable 18 in the Supplement ) indicated that individually, at any 1 site the association was not significant ( Table 2 and Figure 4 B and D).
clause the extractor read what became the number
Where it lands on the map
Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.
What it adds to each cell
For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.
Sulfonylureas & glinides×adverse events & safety
No readable resultOpen on the map →What to test next →7 readable studies in this cell: 0 favour the treatment, 6 find no difference, 1 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
Sulfonylureas & glinides×cardiovascular events
No readable resultOpen on the map →What to test next →3 readable studies in this cell: 2 favour the treatment, 1 find no difference, 0 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 4 syntheses or guidelines pooled it, 66 citations in OpenAlex.
- RETRACTED: Cardiovascular and mortality outcomes of DPP-4 inhibitors vs. sulfonylureas as metformin add-on therapy in patients with type 2 diabetes: A systematic review and meta-analysis.PloS one · 2025 · on this mapPooled it
- Proton pump inhibitors and chronic kidney disease risk: a comparative study with histamine-2 receptor antagonists.Scientific reports · 2023Pooled it
- Distributed Quasi-Poisson regression algorithm for modeling multi-site count outcomes in distributed data networks.Journal of biomedical informatics · 2022Pooled it
- Aspirin, metformin, and statin use on the risk of gastric cancer: A nationwide population-based cohort study in Korea with systematic review and meta-analysis.Cancer medicine · 2022Pooled it
- Article
- Glaucoma Risk with Metformin and Sulfonylurea Therapies in Type 2 Diabetes: A Retrospective Cohort Study.Clinical ophthalmology (Auckland, N.Z.) · 2026Article
- Comparative effectiveness of metformin and alogliptin combination therapy versus metformin monotherapy in patients with type 2 diabetes: an emulated target trial.BMC endocrine disorders · 2025Article
- Disparities in Time to Diagnosis of Radiographic Axial Spondyloarthritis.The Journal of rheumatology · 2025Observational
- OHDSI Standardized Vocabularies-a large-scale centralized reference ontology for international data harmonization.Journal of the American Medical Informatics Association : JAMIA · 2024Article
- Second-Line Pharmaceutical Treatments for Patients with Type 2 Diabetes.JAMA network open · 2023Article
- The Stanford Medicine data science ecosystem for clinical and translational research.JAMIA open · 2023Article
- The Role of Data Science in Closing the Implementation Gap.Critical care clinics · 2023Review
- Risk Assessment of Postoperative Pneumonia in Cancer Patients Using a Common Data Model.Cancers · 2022Article
- Causal deep learning reveals the comparative effectiveness of antihyperglycemic treatments in poorly controlled diabetes.Nature communications · 2022Article
- Adjusting for indirectly measured confounding using large-scale propensity score.Journal of biomedical informatics · 2022Article
- Distributed learning for heterogeneous clinical data with application to integrating COVID-19 data across 230 sites.NPJ digital medicine · 2022Article
- Article
- Incidence and Survival Outcomes of Colorectal Cancer in Long-Term Metformin Users with Diabetes: A Population-Based Cohort Study Using a Common Data Model.Journal of personalized medicine · 2022Article
- An efficient and accurate distributed learning algorithm for modeling multi-site zero-inflated count outcomes.Scientific reports · 2021Article
- Data Consult Service: Can we use observational data to address immediate clinical needs?Journal of the American Medical Informatics Association : JAMIA · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 9 institutions in 2 countries.
Funding
Abstract
The marked sentences are the ones the graph read a number from.
Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Exposures: Treatment with sulfonylureas, DPP-4 inhibitors, or thiazolidinediones starting at least 90 days after the initial prescription of metformin. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: The examined drug classes did not differ in lowering HbA1c and in hazards of kidney disorders in patients with T2D treated with metformin as a first-line therapy. Sulfonylureas had a small, higher observed hazard of myocardial infarction and eye disorders compared with DPP-4 inhibitors in the meta-analysis. The OHDSI collaborative network can be used to conduct a large international study examining the effectiveness of second-line treatment choices made in clinical management of T2D.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.