Randomised controlled trialindependent cross-checkabstract only checked★ key study I-INS-02 in-depth review
UKPDS legacy: 10 years after the trial
10-year follow-up of intensive glucose control in type 2 diabetes.
Overview
Holman RR et al.. N Engl J Med 2008 · PMID 18784090 · DOI 10.1056/NEJMoa0806470
People treated intensively early with sulfonylureas or insulin had 15% fewer heart attacks and 13% fewer deaths years later.
Does the study support the specific claim? No · Methodological quality: high
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Do UKPDS benefits persist and do macrovascular effects emerge?
- How was the study done?
Post-trial monitoring of an RCT (UKPDS 80)
- How many people, animals or samples were studied?
4,209 randomised; 3,277 monitored; Newly diagnosed type 2 diabetes from UKPDS
- What was actually found?
Legacy reductions in MI and death.
- How large was the observed effect?
Death -13% (SU/insulin), -27% (metformin)
- What do the results mean in everyday life?
Early good control pays off for decades.
- What are the study's limitations?
Post-trial therapy not controlled; Questionnaire follow-up
- What does it say about Elawady's specific claim?
Contradicts C-INS-03, C-INS-05 and C-DIAB-01: early insulin/SU therapy reduced MI and death long-term.
- Do the results apply to Germany and Europe?
UK; directly relevant.
- What can explicitly not be concluded from this study?
Effects of extreme targets in late disease.
Scientific in-depth review
1. Full reference
- Authors
- Holman RR et al.
- Journal
- N Engl J Med
- Year
- 2008
- Identifier
- PMID 18784090 DOI 10.1056/NEJMoa0806470
- Verification
- verified – PubMed efetch 2026-10-25 (this agent)
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
not stated in abstract
2. Research question
Do UKPDS benefits persist and do macrovascular effects emerge?
3. Study design and population
- Study design
- Randomised controlled trial – Post-trial monitoring of an RCT (UKPDS 80)
- Population
Newly diagnosed type 2 diabetes from UKPDS
- Country
UK
- Period
10 years post-trial (total up to about 20 years)
- Sample size
4,209 randomised; 3,277 monitored
- Inclusion and exclusion criteria
As described in the abstract; details not available in abstract.
4. Methods and endpoints
- Exposure / intervention
Original intensive therapy (SU/insulin; metformin in overweight)
- Comparator
Conventional (diet)
- Endpoints
Seven aggregate clinical outcomes
- Statistical methods
Intention to treat by original randomisation
5. Actual results
- Results
HbA1c differences lost after 1 year. SU-insulin: any diabetes endpoint -9% (P=0.04), microvascular -24% (P=0.001), MI -15% (P=0.01), death -13% (P=0.007). Metformin: any endpoint -21%, MI -33%, death -27% (P=0.002).
- Absolute risks
not reported
- Authors' conclusion
Continued microvascular risk reduction and emergent reductions in MI and death over 10 years post-trial ('legacy effect').
6. Strengths
- Very long follow-up of randomised groups
7. Weaknesses
- Post-trial therapy not controlled
- Questionnaire follow-up
8. Risk of bias
- Orienting tool
- RoB 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Post-trial phase observational within randomised groups.
9. Assessment of the statistical interpretation
Intention-to-treat comparisons preserve randomisation.
10. Relevance to the specific claim
Contradicts C-INS-03, C-INS-05 and C-DIAB-01: early insulin/SU therapy reduced MI and death long-term.
11. Independent contrary findings
12. Transferability to Germany and Europe
UK; directly relevant.
13. Overall methodological judgement
Key evidence of long-term benefit of early glucose control including insulin.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | high |
| Risk of bias | some concerns |
| Precision of results | moderate |
| Directness | direct |
| Reproducibility | not replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
None beyond those stated.
15. Linked fact checks
- Insulin (and injected insulin) is a principal driver of atherosclerosis. – Studies contradicting or limiting the claim
- Large trials in type 2 diabetes showed that intensive glucose lowering towards normal HbA1c can be harmful: ACCORD was stopped after intensive therapy raised all-cause mortality by 22%, and severe hypoglycaemia was associated with roughly doubled mortality. – Studies contradicting or limiting the claim
- Insulin therapy in type 2 diabetes roughly doubles all-cause mortality and raises cancer, renal and cardiovascular events, with a dose-response (each extra IU/kg/day +54% mortality), compared with metformin or sulfonylureas. – Studies contradicting or limiting the claim
- Metformin (Glucophage) disrupts normal metabolism and causes lactic acidosis (automatically, by blocking the Cori cycle). – Studies contradicting or limiting the claim
- Sulfonylureas cause more myocardial infarctions, strokes and deaths than metformin (21% higher in 253,690 veterans). – Studies contradicting or limiting the claim
- High blood sugar is not a disease but the body's protective response that 'rescues' you; there is no such thing as diabetes ('drink sugar'); sugar intake has no upper limit; HbA1c is a lie. – Studies contradicting or limiting the claim