ADA 2019—After 50 years of waiting: linagliptin and glimepiride do not differ in CVD outcomes

  • Emily Willingham, PhD
  • Conference Reports
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  • Much-anticipated results of the CAROLINA study show that linagliptin is noninferior to glimepiride for a composite of cardiovascular disease (CVD) outcomes in people with type 2 diabetes (T2D).

Why this matters

  • Glimepiride can be less expensive, so results mean patents do not have to balance economics against CVD risk concerns that had initially been raised about sulfonylureas.
  • Findings “provide a clear answer to vindicate sulfonylureas…from the old cardiovascular stigma,” said principal investigator Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City and clinical professor of medicine at the University of Texas Southwestern Medical Center in Dallas, Texas, in a statement .

Key results

  • The primary endpoint, noninferiority for composite of cardiovascular death/nonfatal myocardial infarction/stroke (major adverse cardiac event, MACE), was met: 11.8% with linagliptin vs 12.0% with glimepiride (HR, 0.98; 95% CI, 0.84-1.14).
  • Outcomes were also similar with unstable angina added in (13.2% linagliptin vs 13.3% glimepiride).
  • Authors also note a safety advantage with linagliptin (a dipeptidyl peptidase-4 inhibitor): higher glycemia risk with glimepiride (38% vs 11% with linagliptin), as is common with sulfonylureas.
  • Treatment sustainability was higher with linagliptin: 16.0% vs 10.2% (secondary composite endpoint).

Study design

  • Randomized, double-blind, active-controlled, multicenter trial, 2010-2018, with 6033 adults with T2D (ages 40-85 years), median 6.3 years of observation while taking 5 mg linagliptin once a day or up to 4 mg glimepiride daily.
  • Outcome: MACE.
  • Funding: Boehringer Ingelheim; Eli Lilly and Company.


  • Unknown if outcomes apply to other sulfonylureas.