Cohort studyindependent cross-checkabstract checked★ key study I-INS-124 in-depth review
Long-term glargine use and breast cancer in UK women
Long-Term Use of Long-Acting Insulin Analogs and Breast Cancer Incidence in Women With Type 2 Diabetes.
Overview
Wu JW et al.. J Clin Oncol 2017 · PMID 28953430 · DOI 10.1200/JCO.2017.73.4491
After more than 5 years, glargine users had about twice the breast-cancer rate of NPH users, mainly among women who had used other insulin before.
Does the study support the specific claim? Partly · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Study long-term glargine and breast cancer.
- How was the study done?
UK database cohort.
- How many people, animals or samples were studied?
22,395 women.
- What was actually found?
HR 1.44 overall; 2.23 after >5 years.
- How large was the observed effect?
About 1.5-4 extra cases per 1000 person-years if causal (illustrative).
- What do the results mean in everyday life?
A possible long-term signal that needs confirmation.
- What are the study's limitations?
Observational; not replicated.
- What does it say about Elawady's specific claim?
Partly supports the breast-cancer part.
- Do the results apply to Germany and Europe?
UK data.
- What can explicitly not be concluded from this study?
Cannot prove glargine causes breast cancer.
Scientific in-depth review
1. Full reference
- Authors
- Wu JW et al.
- Journal
- J Clin Oncol
- Year
- 2017
- Identifier
- PMID 28953430 DOI 10.1200/JCO.2017.73.4491
- Verification
- verified – PubMed efetch 2026-10-26; Crossref 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
not stated in abstract
2. Research question
Is long-term use of long-acting insulin analogues associated with breast cancer?
3. Study design and population
- Study design
- Cohort study – Population-based cohort (UK CPRD), long-acting analogues vs NPH
- Population
Women >=40 with T2D treated with glargine, detemir or NPH
- Country
United Kingdom
- Period
2002-2012, follow-up to 2015
- Sample size
22,395 women; 321 breast cancers
- Inclusion and exclusion criteria
Insulin users in CPRD
4. Methods and endpoints
- Exposure / intervention
Glargine or detemir
- Comparator
NPH insulin
- Endpoints
Incident breast cancer
- Statistical methods
Cox models by duration and cumulative dose
5. Actual results
- Results
Glargine vs NPH HR 1.44 (1.11-1.85); after >5 years HR 2.23 (1.32-3.77); >30 prescriptions HR 2.29 (1.26-4.16); elevated in prior insulin users (HR 1.53, 1.10-2.12) but not significant in new users; detemir HR 1.17 (0.77-1.77). Incidence 3.3 per 1000 person-years.
- Absolute risks
Incidence 3.3/1000 PY overall; absolute excess not reported
- Authors' conclusion
Long-term use of insulin glargine is associated with an increased risk of breast cancer in women with T2D.
6. Strengths
- Long follow-up (up to 12 years)
- Duration and dose analyses
- Active comparator (NPH)
7. Weaknesses
- Observational
- Signal mainly in prevalent (prior) insulin users
- Same database and research group as earlier CPRD signal (A-INS-06), so not independent
8. Risk of bias
- Orienting tool
- ROBINS-E
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Prevalent-user and channelling bias possible.
9. Assessment of the statistical interpretation
CIs symmetric; rough absolute excess about 1.5-4 per 1000 PY if causal (stats/C-INS-06_wu2017.py).
10. Relevance to the specific claim
Best support for the long-term breast-cancer part of the claim; conflicts with larger new-user cohorts (I-INS-125, I-INS-127) and does not support a dose-dependent increase of all cancers.
11. Independent contrary findings
Bradley 2020 (I-INS-125), Peeters 2016 (I-INS-127), ORIGIN (A-INS-07, I-INS-05).
12. Transferability to Germany and Europe
Directly applicable; same biology and clinical standards in Europe.
13. Overall methodological judgement
A real but unconfirmed signal.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | moderate |
| Directness | direct |
| Reproducibility | not replicated |
| Consistency with the overall evidence | inconsistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
15. Linked fact checks
- Insulin glargine increases cancer risk in a dose-dependent way (and long-term use increases breast cancer). – Studies supporting the claim