Abstract 14434: Impact of Linagliptin on Cardiovascular (CV) Risk in Type 2 Diabetes (T2D): Insights From a Pre-defined CV Meta-Analysis
Incidence of CV events is increased in T2D but the potential for CV risk modulation with glucose-lowering agents is debated. Interestingly, several CV meta-analyses involving drugs from the class of DPP-4 inhibitors have indicated a potential benefit. This pre-specified meta-analysis of 19 double-blind RCTs (≥ 12 weeks) assessed the CV effects of linagliptin (LINA) treatment versus placebo or active controls (CTRL) in 9459 participants with T2D. CV events were prospectively adjudicated (blinded independent committee). The primary endpoint was a composite of CV death, non-fatal stroke, non-fatal MI and hospitalization for unstable angina, but other CV endpoints were also assessed. Results are given as hazard ratio (HR) for time to first occurrence of any components of the primary endpoint (Cox regression model). Comparative data for traditional CV risk factors across treatment groups are reported descriptively. 5847 received LINA (5 mg: 5687, 10 mg: 160) and 3612 CTRL (placebo: 2675, glimepiride: 775, voglibose: 162). Cumulative exposure (person years) was 4421.3 for LINA and 3254.7 for CTRL. At baseline, clinical characteristics were similar across treatment groups. Incidence rates (IR) of the primary endpoint (/1000 years at risk) were lower for LINA than CTRL (13.4 vs 18.9) and the HR for the primary endpoint was 0.78 (95% CI 0.55, 1.12). IRs for CV death were 2.4 for both and classical MACE were 9.3 and 14.0/1000 pt/yr for LINA and CTRL; respectively leading to corresponding HRs of 1.04 (0.42, 2.60) and 0.74 (0.49, 1.13). Changes from baseline for traditional CV risk factors were generally similar across groups (TABLE). In conclusion, this analysis of adjudicated CV events continues to support that LINA is not associated with an increased CV risk. Potential CV benefits with LINA will be tested prospectively in > 14000 patients in CAROLINA (vs. glimepiride) (NCT01243424) and CARMELINA (vs. standard of care).
- © 2013 by American Heart Association, Inc.