CAROLINA Trial: Linagliptin vs. Glimepiride in T2DM

Year: 2019 Title: CAROLINA TRIAL Subtitle: Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes Type of Trial: An International, Randomised, Parallel Group, Double Blind Trial

Objective: To assess cardiovascular outcomes of linagliptin vs glimepiride (sulfonylurea) in patients with relatively early type 2 diabetes and risk factors for or established atherosclerotic cardiovascular disease.

Participants: 6033

Inclusion Criteria:

  • Age 40-85 years
  • BMI ≤45kg/m^2
  • Type 2 diabetes
  • Elevated glycosylated haemoglobin (HbA1c)
  • Pre-existing cardiovascular disease OR specified diabetes end-organ damage
  • Stable anti-diabetic background for at least 8 weeks before study start


  • Linagliptin (5 mg once daily) (n=3023)
  • Glimepiride (1-4 mg once daily) (n=3010)

Primary Outcome:

  • Occurrence of cardiovascular death, nonfatal MI, or nonfatal stroke in participants (3P-MACE) %
  • Linagliptin Group: 11.8%
  • Glimepiride Group: 12.0%
  • HR, 0.98 (P<0.001 for noninferiority)

Secondary Outcomes:

  1. Occurrence of cardiovascular death, nonfatal MI, or nonfatal stroke & hospitalization in participants (4P-MACE) %
    • Linagliptin Group: 13.2%
    • Glimepiride Group: 13.3%
  2. Participants having change in laboratory parameters related to diabetes from baseline to final visit %
    • Linagliptin Group: 16.0%
    • Glimepiride Group: 10.2%
    • HR, 0.35; 95% CI 0.20-0.61; p < 0.001

Conclusion: Among adults with relatively early type 2 diabetes and elevated cardiovascular risk, the use of linagliptin compared with glimepiride over a median 6.3 years resulted in a noninferior risk of a composite cardiovascular outcome.

Reference: Julio Rosenstock et al. JAMA. 2019;322(12):1155-1166

Comments are closed.