Linagliptin and glimepiride have comparable CV safety effects in type 2 diabetes (T2DM) at high CV risk, show data of the CAROLINA trial, presented at the Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain.

The CAROLINA trial evaluated and compared the effects of linagliptin, a DPP-4 inhibitor, and glimepiride, an SU medication, on CV morbidity and mortality in patients with T2D associated with CV disease and/or CV risk factors. CAROLINA is the only CV safety study that has so far included an active-comparator and in a double-blinded manner compared two commonly used diabetes medications that both lower glucose levels by stimulating the body’s insulin production, however by different mechanisms.

The CAROLINA trial was an international study conducted from 2010 to 2018 in 6,033 adults with T2D from more than 600 sites across 43 countries. The participants had a median disease duration of 6.3 years and were randomly assigned to receive either 5 mg, once daily, of linagliptin, or a daily dose of up to 4 mg of glimepiride. The participants took the study medication in addition to their usual diabetes medications and investigators were advised to attempt to improve glucose control according to local guidelines avoiding the use of incretin-related therapies.

Over 6.3 years median of follow-up, there were no significant differences between linagliptin and glimepiride in the occurrence of CV events. However, with glimepiride, there was a significant and clinically relevant higher risk of hypoglycemia classified as mild, moderate, severe or requiring hospitalization. Further, modest weight gain was observed in participants in the glimepiride group.

Specifically, the primary outcome, a composite of CV death, non-fatal myocardial infarction and non-fatal stroke, when comparing the 3023 participants receiving linagliptin and 3010 receiving glimepiride, showed HR: 0.98 (95%CI: 0.84-1.13), while the corresponding HRs for CV mortality and non-CV mortality were 1.00 (95%CI: 0.81-1.24) and 0.82 (95%CI: 0.66-1.03). There was no overall difference between the treatment groups in HbA1c, while an average between-group difference in weight -1.5 kg (95%CI: –1.8 to –1.3) was seen favoring linagliptin.

Incidence of hypoglycemia was significantly less frequent with linagliptin (10.6%) vs glimepiride (37.7%). Participants having 1 or more investigator-reported episodes of hypoglycemia, yielded a lower HR for first occurrence of hypoglycemia of 0.23 (95%CI: 0.21-0.26) for linagliptin vs glimepiride. This translated to a number needed to treat (NNT) of 3 over 6 years, to prevent 1 episode of hypoglycemia. The same magnitude of relative reduction in risk for hypoglycemia was observed across all severity categories of hypoglycemia, e.g., severe hypoglycemia that affected 0.3% vs 2.2% of participants, providing an HR of 0.15 (95%CI: 0.08-0.29), and corresponding NNT 45.

Source: press release EASD September 19, 2019