Semaglutide for primary prevention of major adverse cardiac and cerebrovascular events in patients with type 2 diabetes and comorbid rheumatoid arthritis: a target-trial emulation
Main finding · Incident MACCE (composite of all-cause mortality, MI, HF, or stroke)Result — go to the resultHazard ratio 0.75 95% CI 0.60–0.94Authors' conclusion
Among obese adults with T2DM and comorbid RA, initiation of semaglutide was associated with a reduced risk of incident MACCE, driven predominantly by a reduction in incident HF, in a primary-prevention setting. Prospective studies are needed to confirm these observations and establish causality.
Study context
- Population
- Obese adults (aged ≥18 years; Body mass index (BMI) ≥30 kg/m²) with T2DM and comorbid rheumatoid arthritis (RA) and no prior history of stroke, heart failure (HF), acute coronary syndrome, or coronary revascularization1,200 semaglutide and 2972 non-GLP-1RA initiators identified, after PS matching, 1017 vs 1017 · semaglutide initiators identified 1,200 · non-GLP-1RA initiators identified 2,972
- Participants
- 1,017 vs 1,017
- Exposure
- patients initiating semaglutide with those initiating non-GLP-1 receptor agonist (GLP-1RA) second-line glucose-lowering therapies
- semaglutiden = 1,017
- non-GLP-1RAn = 1,017reference
- Outcome
- Incident major adverse cardiovascular and cerebrovascular events (MACCE):
- Composite of all-cause mortality
- MI
- HF
- Stroke
- Follow-up
- Up to 2 years
Methodological detailsnew-user design, propensity-score matching (1:1), TriNetX US database, primary-prevention setting
- New-user design
- Propensity-score matching (1:1)
- TriNetX US database
- Primary-prevention setting
Main finding
As reported in the abstract
Incident MACCE:
- Composite of all-cause mortality
- MI
- HF
- Stroke
Hazard ratio
0.75
95% CI 0.60–0.94
P = 0.01
By group
Semaglutide vs non-GLP-1RA
HR 0.75 (95% CI 0.60–0.94); P = 0.01
Observational data: associations, not effects.
Secondary outcomes
| Outcome | Semaglutide | non-GLP-1RA | HR (95% CI) | P value | |
|---|---|---|---|---|---|
| Incident HF | 8.9% | 12.5% | 0.69 (0.53–0.91) | P = 0.007 | |
| DMARD escalation | 16.6% | 21.6% | 0.75 (0.60–0.90) | P = 0.003 | |
| 0.512Hazard ratio (log scale) |
All-cause mortality, myocardial infarction (MI), stroke
- No significant differences were observed in all-cause mortality, MI, or stroke
Original publication
Semaglutide for primary prevention of major adverse cardiac and cerebrovascular events in patients with type 2 diabetes and comorbid rheumatoid arthritis: a target-trial emulation. Eur Heart J Cardiovasc Pharmacother. Published 23 June 2026. doi:10.
Summarised from the published abstract; every number is checked against it