Cardiometabolic & kidneyCohort study

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 PharmacotherPublished

  • target-trial emulation
  • new-user design
  • propensity-score matching (1:1)
  • TriNetX US database
  • primary-prevention setting

Authors' 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

Main finding

As reported in the abstract

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

Outcomesemaglutidenon-GLP-1RAHR (95% CI)P value
Incident HF8.9%12.5%0.69 (0.53–0.91)P = 0.007
DMARD escalation16.6%21.6%0.75 (0.60–0.90)P = 0.003

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:10.1093/ehjcvp/pvag044

Summarised from the published abstract; every number is checked against it