SynthesisPloS one2014
Conventional hypoglycaemic agents and the risk of lung cancer in patients with diabetes: a meta-analysis.
Synthesis in PloS one, 2014. The graph read 17 numbers from its abstract, feeding 7 cells of the map, but none could be read as for or against, so it casts no vote. It also reports 5 associations that do not count as treatment evidence, such as difference -0.87 (-0.94 to -0.81) for glycemic control. Cited by 17 papers, 1 of them a synthesis 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.
Read, but not usablea number the graph found but could not read as for or against
The summary OR of studies that adjusted for other glucose-lowering drugs was 0.87 (95% CI 0.81 to 0.94).
Moreover, sulfonylurea or TZDs use was not associated with increased or decreased lung cancer risk, respectively (OR 1.10, 95% CI 0.93 to 1.26), (OR 0.86, 95% CI 0.70 to 1.02).
Separate pooled post-hoc analysis of two RCTs revealed no significant association between metformin and lung cancer (OR 0.65, 95% CI 0.33 to 1.26; P = 0.22 for heterogeneity) [27].
Moreover, sulfonylurea or TZDs use was not associated with increased or decreased lung cancer risk, respectively (OR 1.10, 95% CI 0.93 to 1.26), (OR 0.86, 95% CI 0.70 to 1.02).
RESULTS: Analysis of 15 studies (11 cohort studies, 2 case-control studies, and 2 RCTs) showed that metformin use was associated with a 15% reduction in risk of lung cancer (OR 0.85, 95% CI 0.77 to 0.92), but this finding was not supported by sub-analysis of smoking-adjusted studies (OR 0.84, 95% CI 0.61 to 1.06).
RESULTS: Analysis of 15 studies (11 cohort studies, 2 case-control studies, and 2 RCTs) showed that metformin use was associated with a 15% reduction in risk of lung cancer (OR 0.85, 95% CI 0.77 to 0.92), but this finding was not supported by sub-analysis of smoking-adjusted studies (OR 0.84, 95% CI 0.61 to 1.06).
Sulfonylureas use was not associated with lung cancer risk in patients with diabetes (OR 1.10, 95% CI 0.93 to 1.26; P = 0.000 for heterogeneity) (Figure 2c) [9], [10], [15], [17], [35].
A subgroup analysis of Western populations pointed out that sulfonylurea use did not modify lung cancer risk (OR 1.09, 95% CI 0.92 to 1.25).
Higher lung cancer risk was related to insulin (OR 1.23, 95% CI 1.10 to 1.35).
Meta-analysis of all 8 observational studies reported that the metformin use was associated with a statistically significant 15% reduction in lung cancer incidence (OR 0.85, 95% CI 0.77 to 0.92 P = 0.003 for heterogeneity) (Figure 2a) [9], [10], [12], [13], [15], [17], [33], [35].
A subgroup analysis of seven Western populations showed that metformin exposure was linked to a 13% reduction in lung cancer risk (OR 0.87, 95% CI 0.81 to 0.94).
On replacing this study with similar population-based cohort studies from the same Taiwanese population, where Chang et al. [38] was replaced for sulfonylureas and insulin and where Hsieh et al. [39] was replaced for metformin, there was no significant change in overall association of lung cancer with sulfonylureas (OR 1.05, 95% CI 0.90 to 1.20), insulin (OR 1.36, 95% CI 1.18 to 1.53), or metformin (OR 0.86, 95% CI 0.79 to 0.92).
The conclusions of the main analysis did not change for metformin (OR 0.81, 95% CI 0.67 to 0.95), sulfonylureas (OR 1.09, 95% CI 0.96 to 1.23), TZDs (OR 0.84, 95% CI 0.6 to 1.09) or insulin (OR 1.25, 95% CI 1.06 to 1.44).
The result of studies that adjusted for smoking illustrated that insulin still increased lung cancer risk (OR 1.30, 95% CI 1.09 to 1.51).
Moreover, post-hoc analysis of two RCTs also showed no significant effect of sulfonylureas on lung cancer (OR 1.56, 95% CI 0.75 to 3.26; P = 0.57 for heterogeneity) [27].
Insulin use was associated with a statistically significant 22% increase in lung cancer risk in patients with diabetes on meta-analysis of eight observational studies (OR 1.23 95% CI 1.10 to 1.35 P = 0.096 for heterogeneity) (Figure 2d) [9], [10], [14], [16], [17], [33], [35], [37].
The summary OR of studies that adjusted for other glucose-lowering drugs was 1.22 (95% CI 1.17 to 1.27).
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.
Insulin×glycemic control
No readable resultOpen on the map →What to test next →40 readable studies in this cell: 14 favour the treatment, 14 find no difference, 13 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.
Metformin×adverse events & safety
No readable resultOpen on the map →What to test next →22 readable studies in this cell: 8 favour the treatment, 8 find no difference, 6 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.
Metformin×pharmacokinetics & dosing
No readable resultOpen on the map →What to test next →2 readable studies in this cell: 0 favour the treatment, 2 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.
Metformin×glycemic control
No readable resultOpen on the map →What to test next →40 readable studies in this cell: 40 favour the treatment, 13 find no difference, 8 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.
Other glucose-lowering×glycemic control
No readable resultOpen on the map →What to test next →8 readable studies in this cell: 4 favour the treatment, 0 find no difference, 4 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×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×glycemic control
No readable resultOpen on the map →What to test next →31 readable studies in this cell: 7 favour the treatment, 13 find no difference, 11 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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Metformin Use and Lung Cancer Risk in Diabetic Patients: A Systematic Review and Meta-Analysis.Disease markers · 2019 · on this mapPooled it
- The therapeutic value of antidiabetic drugs in lung cancer treatment: from clinical evidence to possible mechanisms.Frontiers in immunology · 2026Review
- Pioglitazone-Based Combination Approaches for Non-Small-Cell Lung Cancer.Pharmaceutics · 2025Review
- Association between antidiabetic drugs and cancer risk in patients with type 2 diabetes mellitus: A systematic review and network meta-analysis.World journal of diabetes · 2025Article
- Analysis of factors influencing lung cancer in patients with type 2 diabetes mellitus.Medicine · 2025Observational
- Effects of Hypoglycemic Agents on Pulmonary Diseases: A Comprehensive Narrative Review.Journal of inflammation research · 2025Review
- Article
- Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes.Drug design, development and therapy · 2023Review
- The Effects of 6 Common Antidiabetic Drugs on Anti-PD1 Immune Checkpoint Inhibitor in Tumor Treatment.Journal of immunology research · 2022Article
- Does metformin improve the efficacy of standard epidermal growth factor receptor-tyrosine kinase inhibitor treatment for patients with advanced non-small-cell lung cancer?Interactive cardiovascular and thoracic surgery · 2021Article
- Expanding the Structural Diversity of DNA Methyltransferase Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Effect of type 2 diabetes and antihyperglycemic drug therapy on signs of tumor invasion in papillary thyroid cancer.Endocrine · 2020Article
- Cancer Biology and Prevention in Diabetes.Cells · 2020Review
- Diabetes and Lung Disease: A Neglected Relationship.The review of diabetic studies : RDS · 2019Review
- Human Insulin Therapy Is Associated With an Increased Risk of Lung Cancer: A Population-Based Retrospective Cohort Study.Frontiers in endocrinology · 2019Article
- Alpha-glucosidase inhibitors and risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis.Oncotarget · 2017Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 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.
backgroundAccumulating evidence suggests that hypoglycaemic agents influence lung cancer risk in patients with diabetes. It remains to be fully elucidated whether conventional hypoglycaemic agents (metformin, sulfonylureas, thiazolidinediones [TZDs] or insulin) affect lung cancer incidence in patients with diabetes.
methodsWe performed a meta-analysis using EMBASE, MEDLINE and Web of Science to search randomised controlled trials (RCTs), cohort studies, and case-control studies published up to October 2013 that assessed the effects of metformin, sulfonylurea, TZDs or insulin on lung cancer risk in subjects with diabetes. Fixed and random effects meta-analysis models were used, and the effect size was expressed as a summary odds ratio (OR) with 95% confidence intervals (CI). The Grades of Research, Assessment, Development and Evaluation (GRADE) approach was applied to define the quality of the evidence.
resultsAnalysis of 15 studies (11 cohort studies, 2 case-control studies, and 2 RCTs) showed that metformin use was associated with a 15% reduction in risk of lung cancer (OR 0.85, 95% CI 0.77 to 0.92), but this finding was not supported by sub-analysis of smoking-adjusted studies (OR 0.84, 95% CI 0.61 to 1.06). Moreover, sulfonylurea or TZDs use was not associated with increased or decreased lung cancer risk, respectively (OR 1.10, 95% CI 0.93 to 1.26), (OR 0.86, 95% CI 0.70 to 1.02). Higher lung cancer risk was related to insulin (OR 1.23, 95% CI 1.10 to 1.35). However, all data from RCTs failed to demonstrate a statistically significant effect.
conclusionsThis analysis demonstrated that metformin use may reduce lung cancer risk in patients with diabetes but not in a smoking-adjusted subgroup and that insulin use may be associated with an increased lung cancer risk in subjects with diabetes.
Indexed as
Identifiers
What OpenQuestion holds
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.