T2DM patients on stable metformin (≥1500mg/d) for ≥10 weeks were randomized to linagliptin 5mg/d (N=764) or glimepiride 1−4mg/d (N=755) over 2 years. Efficacy analyses were based on HbA1c change from baseline in the full analysis set (FAS) and per-protocol (PP) population. Safety evaluations included pre-specified, prospective, and adjudicated capture of cardiovascular (CV) events (CV death, non-fatal myocardial infarction or stroke, unstable angina with hospitalization).
Baseline characteristics were well balanced in the 2 groups (HbA1c 7.7% for both). In the PP population, adjusted mean (±SE) HbA1c changes from baseline were −0.4% (±0.04%) for linagliptin 5mg/d vs. −0.5% (±0.04%) for glimepiride (mean dose 3mg/d). Mean between-group difference was 0.17% (95% CI, 0.08-0.27%; p=0.0001 for noninferiority). Similar results were observed in the FAS population. Far fewer patients experienced investigator-defined, drug-related hypoglycemia with linagliptin than glimepiride (7.5% vs. 36.1%; p<0.0001). Body weight was decreased with linagliptin and increased with glimepiride (−1.4 kg vs. +1.3 kg; adjusted mean difference, −2.7kg; p<0.0001). CV events occurred in 13 (1.7%) linagliptin patients vs. 26 (3.4%) glimepiride patients revealing a significant 50% reduction in relative risk for the combined CV endpoint (RR, 0.50; 95% CI, 0.26–0.96; p=0.04).
In conclusion, when added to metformin monotherapy, linagliptin provides similar HbA1c reductions to glimepiride but with less hypoglycemia, relative weight loss, and significantly fewer adjudicated CV events. A long-term outcomes study (CAROLINA; NCT01243424) is ongoing to confirm the promising CV safety data seen with linagliptin to date. [ClinicalTrials.gov, NCT00622284]
Author(s): BAPTIST GALLWITZ, BARBARA UHLIG-LASKE, SUDIPTA BHATTACHARAYA, SANJAY PATEL, HANS-JUERGEN WOERLE: ADA Scientific Sessions Late Breaking Abstract Sunday, June 26, 2011 Abstract -39-LB