Type 2 & other diabetes

Cardioprotective glucose-lowering drugs, statins, and secondary major adverse cardiovascular events: a nationwide cohort study of individuals with type 2 diabetes and cardiovascular disease

Cardiovasc DiabetolPublished Nationwide cohort study

Authors' conclusion

In individuals with type 2 diabetes and established cardiovascular disease, treatment with a cardioprotective glucose-lowering drug and statin in combination was associated with lower risk of secondary major adverse cardiovascular events than using either drug alone. This is important given the persistently suboptimal uptake of both drug classes in real-world practice. Some biases can never be completely excluded in real-world pharmacotherapy use studies such as this one, including confounding by indication, time-related or immortal time biases, and shifting standards of care, rendering causal interpretation unattainable; however, our results seemed consistent across numerous sensitivity analyses and designs.

Study context

Population
Individuals with T2D and established CVD, December 2012 through 2021, Denmarkactive comparator cohort
Participants
15,404 individuals
Exposure
Cardioprotective glucose-lowering drug, statin, or both vs no cardioprotective drug
Outcome
New MACE:
  • MI
  • Stroke
  • Cardiovascular death
Follow-up
Mean 2.7 (active comparator) and 4.7 (time-varying) years
Methodological detailsactive comparator cohort, time-varying cohort, national Danish health registers
  • Active comparator cohort
  • Time-varying cohort
  • National Danish health registers

Main finding

As reported in the abstract

MACE, active comparator cohort · mean 2.7 years
Each group vs no cardioprotective drugMultivariable adjusted hazard ratio (95% CI)
Cardioprotective glucose-lowering drug
0.82(0.67–1.02)
Statin
0.85(0.74–0.97)
Cardioprotective glucose-lowering drug and statin
0.71(0.60–0.84)
MACE events, active comparator cohort
1,843
p for interaction between cardioprotective glucose-lowering drug and statin
> 0.05

Observational data: associations, not effects.

Further findings

OutcomeHR (CI)
MACE, time-varying cohort (n=76,853), multivariable adjusted · mean 4.7 years of follow-upCardioprotective glucose-lowering drugvs No cardioprotective drug0.77 (0.69–0.86)
MACE, time-varying cohort (n=76,853), multivariable adjusted · mean 4.7 years of follow-upStatinvs No cardioprotective drug0.73 (0.70–0.75)
MACE, time-varying cohort (n=76,853), multivariable adjusted · mean 4.7 years of follow-upCardioprotective glucose-lowering drug and statinvs No cardioprotective drug0.57 (0.54–0.60)

MACE, active comparator cohort restricted to individuals entering observation 2019–2021

Corresponding HRs estimated in the restricted cohort, with reduced statistical power

Interaction between cardioprotective glucose-lowering drug and statin

P for interaction, both cohorts
> 0.05

Patients with MACE · mean 2.7 and 4.7 years of follow-up

Active comparator cohort
1,843
Time-varying cohort
23,051

Original publication

Cardioprotective glucose-lowering drugs, statins, and secondary major adverse cardiovascular events: a nationwide cohort study of individuals with type 2 diabetes and cardiovascular disease. Cardiovasc Diabetol. Published 16 June 2026. doi:10.1186/s12933-026-03242-9

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