Randomised controlled trialindependent cross-checkabstract checked★ key study I-ODD-105 in-depth review
Forxiga in 17,160 people: fewer heart-failure admissions, rare ketoacidosis
Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes.
Overview
Wiviott SD et al.. N Engl J Med 2019 · PMID 30415602 · DOI 10.1056/NEJMoa1812389
HF hospitalisation HR 0.73; renal events HR 0.76; DKA 0.3% vs 0.1%.
Does the study support the specific claim? Partly · Methodological quality: high
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Test cardiovascular safety and benefit of dapagliflozin.
- How was the study done?
Blinded RCT vs placebo.
- How many people, animals or samples were studied?
17,160 adults with type 2 diabetes.
- What was actually found?
No change in heart attacks/strokes; fewer heart-failure hospitalisations and kidney events; slightly more DKA and genital infections.
- How large was the observed effect?
HHF HR 0.73 (0.61-0.88); DKA +0.2 percentage points.
- What do the results mean in everyday life?
The drug helps the heart and kidneys; a rare ketoacidosis risk requires precautions.
- What are the study's limitations?
Industry-funded; few DKA events.
- What does it say about Elawady's specific claim?
Supports the DKA part (C-ODD-02); contradicts 'dirtiest drug' and net harm (C-ODD-06).
- Do the results apply to Germany and Europe?
High.
- What can explicitly not be concluded from this study?
Risk during prolonged fasting.
Scientific in-depth review
1. Full reference
- Authors
- Wiviott SD et al.
- Journal
- N Engl J Med
- Year
- 2019
- Identifier
- PMID 30415602 DOI 10.1056/NEJMoa1812389
- Verification
- verified – PubMed efetch 2026-10-26; Crossref works API 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
Funded by AstraZeneca (manufacturer).
2. Research question
What are the cardiovascular effects and safety of dapagliflozin in type 2 diabetes with or at risk of atherosclerotic cardiovascular disease?
3. Study design and population
- Study design
- Randomised controlled trial – Double-blind placebo-controlled randomised trial (DECLARE-TIMI 58)
- Population
Adults with type 2 diabetes and established ASCVD or multiple risk factors (10,186 without ASCVD)
- Country
Multinational
- Period
Median follow-up 4.2 years
- Sample size
17,160
- Inclusion and exclusion criteria
Type 2 diabetes with or at risk of ASCVD
4. Methods and endpoints
- Exposure / intervention
Dapagliflozin
- Comparator
Placebo
- Endpoints
MACE (safety); MACE and CV death/HF hospitalisation (efficacy); renal composite; all-cause death; adverse events incl. DKA
- Statistical methods
Cox models; non-inferiority then superiority testing
5. Actual results
- Results
MACE 8.8% vs 9.4% (HR 0.93, 95% CI 0.84-1.03; non-inferior). CV death or HF hospitalisation 4.9% vs 5.8% (HR 0.83, 0.73-0.95), driven by HF hospitalisation (HR 0.73, 0.61-0.88); CV death HR 0.98 (0.82-1.17). Renal composite 4.3% vs 5.6% (HR 0.76, 0.67-0.87). All-cause death 6.2% vs 6.6% (HR 0.93, 0.82-1.04). DKA 0.3% vs 0.1% (P=0.02); genital infections leading to discontinuation or serious 0.9% vs 0.1%.
- Absolute risks
DKA +0.2 percentage points over about 4.2 years (NNH about 500, rounded); HF hospitalisation/CV death -0.9 percentage points.
- Authors' conclusion
Dapagliflozin did not change MACE but lowered CV death or HF hospitalisation, reflecting fewer HF hospitalisations.
6. Strengths
- Large blinded RCT, long follow-up
- Mostly primary-prevention population (relevant to typical patients)
7. Weaknesses
- Industry-funded
- DKA was a secondary safety outcome with few events
- Abstract only reviewed
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 placebo-controlled design; adjudicated endpoints.
9. Assessment of the statistical interpretation
HR CIs log-symmetric (stats/C-ODD-06.py). DKA tripled in relative terms but the absolute difference is about 2 per 1,000 patients over 4 years; HF/renal benefits are larger in absolute terms.
10. Relevance to the specific claim
Directly concerns dapagliflozin (Forxiga), the drug named by Elawady: confirms rare DKA and refutes net harm.
11. Independent contrary findings
DAPA-HF and DAPA-CKD (I-ODD-04, I-ODD-03) show mortality reductions in heart failure and CKD.
12. Transferability to Germany and Europe
High; multinational trial.
13. Overall methodological judgement
High-quality evidence of a small DKA excess and clear heart-failure and kidney benefit with dapagliflozin.
| 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
Effect in people who fast for long periods.
15. Linked fact checks
- SGLT2 inhibitors such as dapagliflozin (Forxiga) can cause ketoacidosis, sometimes with normal or low blood glucose. – Studies supporting 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