Abstract 978: Cardiovascular Safety of Saxagliptin as Mono- or Add-on Therapy in Patients With Type 2 Diabetes
The long-term cardiovascular (CV) safety of antidiabetic agents has recently come under scrutiny from regulatory agencies and the public. Saxagliptin (SAXA) is a potent and selective DPP-4 inhibitor in development for mono- or combination treatment of Type 2 diabetes (T2D). In preclinical studies, there was no effect on ECG, hERG, or Purkinje assessment, no cardiotoxicity, and SAXA was not associated with clinically significant QTc interval prolongation at doses of 40 mg/day or 400 mg/day. Data from 8 randomized, controlled studies were pooled to assess CV safety. Preferred terms from MedDRA were used to identify events related to acute cardiovascular events (ACE), including cardiac revascularization procedures and major adverse cardiovascular events (MACE) - CV death, non-fatal myocardial infarction, and non-fatal stroke. This meta-analysis included 4,607 patients (5,051 patient years of exposure); 3,356 were treated with SAXA in doses of 2.5–100 mg/day, and 1,251 were treated with a comparator -placebo, metformin, or up-titrated glyburide. The mean age was 54 years for both the SAXA and comparator treatment groups. Within the SAXA treatment group, 81% of patients had at least one CV risk factor in addition to T2D; 52% had hypertension, 44% dyslipidemia, 39% history of smoking, and 12% prior CV disease. The mean duration of follow up with SAXA was 1.12 years and with comparator was 1.03 years. There were 10 (0.3%) deaths in the SAXA group and 12 (1.0%) in the comparator group. The incidence of CV death was low, 0.2% SAXA and 0.8% in the comparator group. A total of 23 (0.7%) patients were identified as having a MACE in the SAXA group and 18 (1.4%) in the comparator group. The number of patients identified as having an ACE was 38 (1.1%) and 23 (1.8%) in the SAXA and comparator groups, respectively. The Cox proportional hazard ratio for MACE was 0.44 (95%CI 0.24 – 0.82) and for ACE was 0.59 (95%CI: 0.35–1.00). Compared with placebo, there were no or minimal changes in blood pressure, LDL-c, HDL-c, triglycerides, or body weight. This evidence suggests no increased CV risk with SAXA treatment and raises the hypothesis of a possible CV benefit. An outcome study is planned to investigate this hypothesis in high-risk diabetics.