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CAROLINA Trial finds no difference in CV risk between linagliptin, glimepiride


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Julio Rosenstock, MD
Julio Rosenstock, MD

In a head-to-head comparison of linagliptin, a DPP-4 inhibitor, and glimepiride, a sulfonylurea, researchers found no difference in risk for cardiovascular (CV) mortality or overall mortality in patients with type 2 diabetes.

First results of the Cardiovascular Outcome Study of Linagliptin versus Glimepiride in Patients with Type 2 Diabetes (CAROLINA) trial were presented Monday, June 10, at the 79th Scientific Sessions. The researchers reported results based on a median follow-up of 6.3 years, the longest-ever follow-up period for a CV outcomes trial in diabetes.

While the researchers determined there were no significant differences between linagliptin and glimepiride on CV events, they found a significantly higher risk of hypoglycemia and modest weight gain in the glimepiride group

“Other than a cost consideration, which is valid, CAROLINA supports the use of a DPP-4 inhibitor (linagliptin) before a sulfonylurea (glimepiride),” said principal investigator Julio Rosenstock, MD, Director of the Dallas Diabetes Research Center at Medical City Dallas and Clinical Professor of Medicine at the University of Texas Southwestern Medical Center. “I will extend that and say cardiovascular safety should no longer be a consideration in the decision-making process for selecting between either of these two oral agents.”

Bernard Zinman, CM, MD
Bernard Zinman, CM, MD, FRCPC, FACP

Study investigator Bernard Zinman, CM, MD, FRCPC, FACP, Professor of Medicine at the University of Toronto, also noted that the CAROLINA results do not challenge current recommendations to base the initial choice of second-line therapy on CV/mortality benefit, and further inform the choice of additional therapies.

“Linagliptin was superior to glimepiride in the context of hypoglycemia,” Dr. Zinman said. “Over a third of glimepiride-treated patients had hypoglycemia, which was greatly reduced by linagliptin despite similar A1C reductions. Linagliptin was associated with a modestly greater mean weight loss relative to glimepiride.”

The CAROLINA trial was conducted from 2010 to 2018 at more than 600 sites in 43 countries. The study featured 6,033 adult participants between age 40 and 85 with type 2 diabetes. Participants had a median disease duration of 6.2 years and either an increased risk of cardiovascular disease (CVD) or established CVD. Participants were randomly assigned to receive a 5 mg daily dose of linagliptin or a daily dose of up to 4 mg of glimepiride in addition to their usual diabetes medications.