Randomised controlled trialindependent cross-checkabstract only checked★ key study I-ODD-02 in-depth review
Empagliflozin heart trial
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.
Overview
Zinman B et al.. N Engl J Med 2015 · PMID 26378978 · DOI 10.1056/NEJMoa1504720
Deaths fell from 8.3% to 5.7% over about 3 years.
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?
CV outcomes of empagliflozin in type 2 diabetes at high CV risk
- How was the study done?
Double-blind placebo-controlled RCT (EMPA-REG OUTCOME)
- How many people, animals or samples were studied?
7,020; Type 2 diabetes with high CV risk
- What was actually found?
Primary 10.
- How large was the observed effect?
HR 0.86; death -32%
- What do the results mean in everyday life?
This drug class protects heart and/or kidneys in the studied patients.
- What are the study's limitations?
Industry funded; Selected high-risk population
- What does it say about Elawady's specific claim?
- Do the results apply to Germany and Europe?
Multinational trial including European sites or directly applicable to EU practice.
- What can explicitly not be concluded from this study?
Benefit in low-risk people; absence of side effects.
Scientific in-depth review
1. Full reference
- Authors
- Zinman B et al.
- Journal
- N Engl J Med
- Year
- 2015
- Identifier
- PMID 26378978 DOI 10.1056/NEJMoa1504720
- Verification
- verified – PubMed efetch 2026-10-25 (this agent)
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
Funded by Boehringer Ingelheim and Eli Lilly.
2. Research question
CV outcomes of empagliflozin in type 2 diabetes at high CV risk
3. Study design and population
- Study design
- Randomised controlled trial – Double-blind placebo-controlled RCT (EMPA-REG OUTCOME)
- Population
Type 2 diabetes with high CV risk
- Country
International
- Period
Median 3.1 years
- Sample size
7,020
- Inclusion and exclusion criteria
As described in the abstract; details not available in abstract.
4. Methods and endpoints
- Exposure / intervention
Empagliflozin 10/25 mg
- Comparator
Placebo on top of standard care
- Endpoints
CV death, MI, stroke
- Statistical methods
Cox proportional hazards, intention to treat
5. Actual results
- Results
Primary 10.5% vs 12.1% (HR 0.86, 0.74-0.99). CV death 3.7% vs 5.9% (-38%); HF hospitalisation 2.7% vs 4.1% (-35%); all-cause death 5.7% vs 8.3% (-32%). More genital infections.
- Absolute risks
All-cause death -2.6 percentage points.
- Authors' conclusion
Lower primary composite and all-cause death.
6. Strengths
- Large blinded RCT
- Adjudicated hard endpoints
7. Weaknesses
- Industry funded
- Selected high-risk population
8. Risk of bias
- Orienting tool
- RoB 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- low
- Rationale
Blinded, adjudicated outcomes.
9. Assessment of the statistical interpretation
Clinically relevant reductions with adequate precision.
10. Relevance to the specific claim
Contradicts C-ODD-06; context for C-ODD-02, C-ODD-08.
11. Independent contrary findings
Adverse effects listed in archive studies.
12. Transferability to Germany and Europe
Multinational trial including European sites or directly applicable to EU practice.
13. Overall methodological judgement
High-quality evidence of benefit.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | high |
| Risk of bias | low |
| Precision of results | high |
| Directness | direct |
| Reproducibility | 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
- SGLT2 inhibitors such as dapagliflozin (Forxiga) can cause ketoacidosis, sometimes with normal or low blood glucose. – Studies contradicting or limiting the claim
- Every major class of glucose-lowering drug (metformin, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 agonists) carries a documented signal of serious harm in the peer-reviewed literature. – Studies contradicting or limiting the claim
- Glucose-lowering drugs are net harmful and belong among the 'forbidden' items; dapagliflozin (Forxiga) is among the 'dirtiest' drugs and kills the brain; leg amputations happen only to people taking diabetes drugs and insulin. – Studies contradicting or limiting the claim