Evidence map›Insulin × adverse events & safety›PMID 29860664›Full record

Observational studyOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2018

Real-world antidiabetic drug use and fracture risk in 12,277 patients with type 2 diabetes mellitus: a nested case-control study.

E Losada, B Soldevila, M S Ali, D Martínez-Laguna, X Nogués, M Puig-Domingo, A Díez-Pérez, D Mauricio, D Prieto-Alhambra

Abstract readObservational Study
PubMed Publisher
In one paragraph

Observational study in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2018. The graph read 1 number from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. Cited by 25 papers, 2 of them syntheses that pooled it.

1number the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 2 pooled it
6.9field-weighted citation impact, top 2% of its field
1 · What the graph read from 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

Adverse events & safetydirection of benefit for this outcome is not defined · head-to-head · t2dfeeds 2 cells of the map
OR 1.631.30 to 2.04
Insulin use was associated with increased fracture risk (adjusted OR 1.63 (95% CI 1.30-2.04)), as was the combination of MTF and sulfonylurea (SU) (adjusted OR 1.29 (1.07-1.56)), compared with MTF monotherapy.
FeedsMetformin×adverse events & safetyInsulin×adverse events & safety

clause the extractor read what became the number

2 · Its place on the map

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.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

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×adverse events & safety

No readable resultOpen on the map →What to test next →

16 readable studies in this cell: 7 favour the treatment, 5 find no difference, 4 favour the comparator.

Belief with this paper
0.09contested · 1 family supports, 8 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT036893742,274 enrolled · 2018
Δ -0.29-0.38 to -0.20
NCT013360231,663 enrolled · 2011
Treatment contrast -0.64-0.75 to -0.53
NCT032680051,264 enrolled · 2017
Δ -0.04-0.11 to 0.03
NCT009606611,036 enrolled · 2009
Δ -0.04-0.18 to 0.11
NCT01117350978 enrolled · 2010
Δ 2.54-3.88 to 8.93
NCT02607306819 enrolled · 2015
Treatment contrast -0.48-0.60 to -0.37
NCT01075282810 enrolled · 2010
Δ -0.45-0.60 to -0.29
NCT01648582774 enrolled · 2012
Δ -0.57-0.74 to -0.40
NCT05259033683 enrolled · 2022
Δ -0.44-0.56 to -0.33
NCT01123980521 enrolled · 2010
Δ -0.12-0.25 to 0.02
NCT02787551514 enrolled · 2016
Δ -0.64-0.77 to -0.51
NCT01676116438 enrolled · 2012
Treatment contrast -0.94-1.11 to -0.78

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: 9 favour the treatment, 8 find no difference, 5 favour the comparator.

Belief with this paper
0.27contested · 4 families support, 11 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017190031,413 enrolled · 2012
Adjusted mean -0.72-0.95 to -0.48
NCT018093271,186 enrolled · 2013
Δ -0.40-0.59 to -0.21
NCT022730501,136 enrolled · 2014
Δ -8.90-13.3 to -4.50
NCT01126580807 enrolled · 2010
Δ -0.22-0.36 to -0.08
NCT01023581784 enrolled · 2009
Δ -0.67-0.96 to -0.37
NCT00386100688 enrolled · 2006
Δ 1.47-14.8 to 20.8
NCT01217073685 enrolled · 2010
Δ 1.00-9.80 to 13.1
NCT01890122647 enrolled · 2013
Δ -0.68-0.89 to -0.47
NCT00727857600 enrolled · 2007
Δ 0.860.51 to 1.22
NCT01958671461 enrolled · 2013
Δ -2.60-13.1 to 8.10
NCT00328172302 enrolled · 2006
Δ -0.85-1.10 to -0.59
NCT01485614200 enrolled · 2012
Δ 2.40-10.0 to 14.9

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · The registry

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.

5 · Its place in the literature

Who cites it

25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.

  1. Pooled it
  2. Risk of fracture with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in real-world use: systematic review and meta-analysis of observational studies.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2019
    Pooled it
  3. Glycemic Control and Insulin Treatment Alter Fracture Risk in Older Men With Type 2 Diabetes Mellitus.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019 · on this map
    Trial
  4. Article
  5. Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025
    Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Fracture risk assessment in diabetes mellitus.Frontiers in endocrinology · 2022
    Review
  12. Review
  13. Diabetes and Bone Fragility.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2021
    Review
  14. Article
  15. Review
  16. Review
  17. TiOInternational journal of nanomedicine · 2020
    Article
  18. Bone health in diabetes and prediabetes.World journal of diabetes · 2019
    Review
  19. Article
  20. Diabetes and bone.Osteoporosis and sarcopenia · 2019
    Review
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

9 authors at 6 institutions in 2 countries.

E LosadaDepartment of Endocrinology and Nutrition, Hospital Can Misses, Eivissa, Spain.
B SoldevilaDepartment of Endocrinology and Nutrition, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s/n. 08916, Badalona, Barcelona, Spain.
M S AliMusculoskeletal Pharmaco- and Device Epidemiology, Centre for Statistics in Medicine, NDORMS, University of Oxford, Oxford, UK.
D Martínez-LagunaGREMPAL Research Group, IDIAP Jordi Gol, Universitat Autònoma de Barcelona, Barcelona, Spain.
X NoguésCIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain.
M Puig-DomingoDepartment of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
A Díez-PérezCIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain.
D MauricioDepartment of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. didacmauricio@gmail.com.
D Prieto-AlhambraMusculoskeletal Pharmaco- and Device Epidemiology, Centre for Statistics in Medicine, NDORMS, University of Oxford, Oxford, UK.
Universitat Autònoma de Barcelona · ESCentro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable · ESCentro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas · ESHospital Can Misses · ESInstitut Universitari d'Investigació en Atenció Primària Jordi Gol · ESUniversity of Oxford · GB

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

We conducted a nested case-control study to study the association between antidiabetic treatments (alone or in combination) use and fracture risk among incident type 2 Diabetes mellitus patients. We found an increased risk of bone fracture with insulin therapy compared to metformin monotherapy.

introductionPatients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures, to which antidiabetic therapies may contribute. We aimed to characterize the risk of fracture associated with different antidiabetic treatments as usually prescribed to T2DM patients in actual practice conditions.

methodsA case-control study was nested within a cohort of incident T2DM patients registered in 2006-2012 in the Information System for Research Development in Primary Care (Catalan acronym, SIDIAP), a database which includes records for > 5.5 million patients in Catalonia (Spain). Each case (incident major osteoporotic fracture) was risk-set matched with up to five same-sex controls by calendar year of T2DM diagnosis and year of birth (± 10 years). Study exposure included previous use of all antidiabetic medications (alone or in combination), as dispensed in the 6 months before the index date, with metformin (MTF) monotherapy, the most commonly used drug, as a reference group (active comparator).

resultsData on 12,277 T2DM patients (2049 cases and 10,228 controls) were analyzed. Insulin use was associated with increased fracture risk (adjusted OR 1.63 (95% CI 1.30-2.04)), as was the combination of MTF and sulfonylurea (SU) (adjusted OR 1.29 (1.07-1.56)), compared with MTF monotherapy. Sensitivity analyses suggest possible causality for insulin therapy but not for the MTF + SU combination association. No significant association was found with any other antidiabetic medications.

conclusionsInsulin monotherapy was associated with an increased fracture risk compared to MTF monotherapy in T2DM patients. Fracture risk should be taken into account when starting a glucose-lowering drug as part of T2DM treatment.

Indexed as

AgedAged, 80 and overCase-Control StudiesDiabetes Mellitus, Type 2Drug UtilizationFemaleHumansHypoglycemic AgentsInsulinMaleMetforminMiddle AgedOsteoporotic FracturesRisk AssessmentSpainHypoglycemic AgentsInsulinMetforminEpidemiologyFracture riskGeneral populationType 2 diabetes mellitus

Identifiers

PMID29860664
OpenAlexW2806021934

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

None linked

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 Socratic graph.