Incidence of cardiovascular (CV) events is increased in type 2 diabetes (T2D) but the potential for CV risk modulation with glucose lowering is debated. Linagliptin, a DPP-4 inhibitor, provides a meaningful reduction in hyperglycaemia and also may have potential CV benefits. To further explore potential mechanisms behind this, we report additional relevant data from a large CV meta-analysis of linagliptin trial data.

In this pre-specified meta-analysis from 8 Phase III randomised, controlled trials, CV events were prospectively adjudicated by a blinded independent expert committee. A composite primary endpoint of CV death, MI, stroke, and hospitalisation for unstable angina pectoris (UAP) was used. Results are given as hazard ratio (HR) for time to first occurrence of any components of the primary endpoint using a Cox regression model for linagliptin vs total comparators with factors of study (grouped by design), treatment (linagliptin vs combined comparators), gender (female vs male), race (Asian vs White), and time since T2D diagnosis (>5 vs ≤5 yr). Comparative data for conventional CV risk factors across treatment groups are reported descriptively.

3319 patients received linagliptin once daily (5mg: 3159, 10mg: 160) and 1920 comparator (placebo: 977, glimepiride: 781, voglibose: 162). The overall study cohort (N=5239) seemed representative of a general T2D population among which overall HR was higher in patients with longer duration of T2D (1.51 [95% CI: 0.75–3.04]) and reduced in females (0.36 [95% CI: 0.16–0.84]) and Asians [0.28 [95% CI: 0.10–0.82]). A significantly reduced risk for the primary endpoint after treatment with linagliptin was indicated by the HR (0.36 [95% CI: 0.17–0.74]). Between-group changes in cholesterol and systolic and diastolic blood pressure were similar for linagliptin- and comparator-treated patients. Linagliptin treatment was associated with a greater reduction in HbA1c (−0.6±0.9%), fasting triglycerides (−11±136mg/dL), and no weight gain (0.01±3.09kg) in contrast to the total comparators (respectively −0.3±1.0%, −6±156mg/dL, and 0.6±3.42kg).

Additional Cox regression analyses support the CV safety profile of linagliptin in a large phase III CV meta-analysis. The low CV HR observed with linagliptin cannot be fully explained by classical CV risk factors such as blood pressure and lipids. Further clinical outcome and mechanistic studies are underway to provide additional insights.