Observational studyAnnals of internal medicine2015
Effects on Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus.
Observational study in Annals of internal medicine, 2015. The graph read 4 numbers from its abstract, feeding 2 cells of the map: it supports the treatment in 1. Cited by 53 papers, 5 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.
RESULTS: DPP-4 inhibitors were associated with lower risks for all-cause death (hazard ratio [HR], 0.63 [95% CI, 0.55 to 0.72]), MACEs (HR, 0.68 [CI, 0.55 to 0.83]), ischemic stroke (HR, 0.64 [CI, 0.51 to 0.81]), and hypoglycemia (HR, 0.43 [CI, 0.33 to 0.56]) compared with sulfonylureas as add-on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure.
RESULTS: DPP-4 inhibitors were associated with lower risks for all-cause death (hazard ratio [HR], 0.63 [95% CI, 0.55 to 0.72]), MACEs (HR, 0.68 [CI, 0.55 to 0.83]), ischemic stroke (HR, 0.64 [CI, 0.51 to 0.81]), and hypoglycemia (HR, 0.43 [CI, 0.33 to 0.56]) compared with sulfonylureas as add-on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure.
RESULTS: DPP-4 inhibitors were associated with lower risks for all-cause death (hazard ratio [HR], 0.63 [95% CI, 0.55 to 0.72]), MACEs (HR, 0.68 [CI, 0.55 to 0.83]), ischemic stroke (HR, 0.64 [CI, 0.51 to 0.81]), and hypoglycemia (HR, 0.43 [CI, 0.33 to 0.56]) compared with sulfonylureas as add-on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure.
RESULTS: DPP-4 inhibitors were associated with lower risks for all-cause death (hazard ratio [HR], 0.63 [95% CI, 0.55 to 0.72]), MACEs (HR, 0.68 [CI, 0.55 to 0.83]), ischemic stroke (HR, 0.64 [CI, 0.51 to 0.81]), and hypoglycemia (HR, 0.43 [CI, 0.33 to 0.56]) compared with sulfonylureas as add-on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure.
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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.
Metformin×all-cause mortality
No readable resultOpen on the map →What to test next →1 readable study in this cell: 0 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.
Sulfonylureas & glinides×all-cause mortality
SupportsOpen on the map →What to test next →No other readable study in this cell yet. This paper is the evidence.
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
53 citing papers in PubMed, 5 syntheses or guidelines pooled it, 101 citations in OpenAlex.
- Safety and efficacy of prusogliptin in type-2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.Irish journal of medical science · 2025Pooled it
- 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
- Global bibliometric analysis of traditional Chinese medicine regulating gut microbiota in the treatment of diabetes from 2004 to 2024.Frontiers in pharmacology · 2025Pooled it
- Pooled it
- Pooled it
- Effectiveness and Safety of Metformin, Teneligliptin, and Glimepiride Combination Therapy in Type 2 Diabetes: A Quasi Experimental Clinical Trial.Current diabetes reviews · 2025Trial
- A prospective cohort study on effects of gemigliptin on cardiovascular outcomes in patients with type 2 diabetes (OPTIMUS study).Scientific reports · 2020Trial
- Which is better, high-dose metformin monotherapy or low-dose metformin/linagliptin combination therapy, in improving glycemic variability in type 2 diabetes patients with insufficient glycemic control despite low-dose metformin monotherapy? A randomized, cross-over, continuous glucose monitoring-based pilot study.Journal of diabetes investigation · 2019Trial
- KASL clinical practice guidelines for liver cirrhosis: Ascites and related complications 2026.Clinical and molecular hepatology · 2026Article
- Comparative cardiovascular risk of sulfonylureas with low- and high-affinities for cardiac mitochondrial adenosine triphosphate-sensitive potassium channels versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: A cohort study.Diabetes, obesity & metabolism · 2025Article
- Association of DPP-4 inhibitors with respiratory and cardiovascular complications in patients with COPD: a nationwide cohort study.ERJ open research · 2025Article
- [Cardiovascular safety of sitagliptin added to metformin in real world patients with type 2 diabetes].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2024Article
- The State of Use and Utility of Negative Controls in Pharmacoepidemiologic Studies.American journal of epidemiology · 2024Review
- Causal relationship between novel antidiabetic drugs and ischemic stroke: a drug-targeted Mendelian randomization study.Frontiers in cardiovascular medicine · 2024Article
- Efficacy and Safety of DPP-4 Inhibitors and Metformin Combinations in Type 2 Diabetes: A Systematic Literature Review and Network Meta-Analysis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Article
- Effect of Dipeptidyl Peptidase-4 Inhibitors vs. Metformin on Major Cardiovascular Events Using Spontaneous Reporting System and Real-World Database Study.Journal of clinical medicine · 2022Article
- Safety of add-on sulfonylurea therapy in patients with type 2 diabetes using metformin: a population-based real-world study.BMJ open diabetes research & care · 2021Article
- Budget Impact of Oral Semaglutide Intensification versus Sitagliptin among US Patients with Type 2 Diabetes Mellitus Uncontrolled with Metformin.PharmacoEconomics · 2021Article
- Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry).BMJ open diabetes research & care · 2021Observational
- [Cardiovascular preventive recommendations. PAPPS 2020 update].Atencion primaria · 2020Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
backgroundRecent studies concluded that dipeptidyl peptidase-4 (DPP-4) inhibitors provide glycemic control but also raised concerns about the risk for heart failure in patients with type 2 diabetes mellitus (T2DM). However, large-scale studies of the effects on cardiovascular outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy remain scarce.
objectiveTo compare clinical outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy in patients with T2DM.
designNationwide study using Taiwan's National Health Insurance Research Database.
settingTaiwan. PATIENTS: All patients with T2DM aged 20 years or older between 2009 and 2012. A total of 10,089 propensity score-matched pairs of DPP-4 inhibitor users and sulfonylurea users were examined. MEASUREMENTS: Cox models with exposure to sulfonylureas and DPP-4 inhibitors included as time-varying covariates were used to compare outcomes. The following outcomes were considered: all-cause mortality, major adverse cardiovascular events (MACEs) (including ischemic stroke and myocardial infarction), hospitalization for heart failure, and hypoglycemia. Patients were followed until death or 31 December 2013.
resultsDPP-4 inhibitors were associated with lower risks for all-cause death (hazard ratio [HR], 0.63 [95% CI, 0.55 to 0.72]), MACEs (HR, 0.68 [CI, 0.55 to 0.83]), ischemic stroke (HR, 0.64 [CI, 0.51 to 0.81]), and hypoglycemia (HR, 0.43 [CI, 0.33 to 0.56]) compared with sulfonylureas as add-on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure. LIMITATION: Observational study design.
conclusionCompared with sulfonylureas, DPP-4 inhibitors were associated with lower risks for all-cause death, MACEs, ischemic stroke, and hypoglycemia when used as add-ons to metformin therapy. PRIMARY FUNDING SOURCE: None.
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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.