Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus and cardiovascular disease history or cardiovascular risk factors: results of a pooled analysis of phase 3 clinical trials.

ABSTRACT

OBJECTIVE: This post hoc analysis sought to assess the efficacy, safety, and tolerability of saxagliptin in patients with type 2 diabetes mellitus and cardiovascular (CV) risk factors or disease (CVD). METHODS: Data from 5 randomized controlled trials were pooled to compare saxagliptin 5 mg with placebo 2 studies of saxagliptin as monotherapy in drug-naïve patients and 1 each of saxagliptin as add-on therapy to metformin, glyburide, or a thiazolidinedione. Analysis was performed according to the following baseline/trial entry criteria 1) history/no history of CVD; 2) ≥ 2 versus 0 to 1 CV risk factors; 3) statin use versus no statin use; and 4) hypertension versus no hypertension. Change from baseline glycated hemoglobin (HbA1c), fasting plasma glucose, and postprandial glucose levels; and the proportion of patients achieving an HbA1c level < 7% were analyzed (week 24). Safety was assessed by adverse events, hypoglycemia, and body weight. RESULTS: In total, 882 patients received saxagliptin 5 mg and 799 received placebo. Differences in adjusted mean change from baseline HbA1c (95% CI) were greater with saxagliptin compared with placebo in patients with a history of CVD (-0.64% [-0.90 to -0.38]) and no history of CVD (-0.68% [-0.78 to -0.58]); with ≥ 2 CV risk factors (-0.73% [-0.85 to -0.60]) and 0 to 1 CV risk factor (-0.62% [-0.75 to -0.48]); with statin use (-0.70% [-0.89 to -0.52]) and no statin use (-0.66% [-0.77 to -0.56]); and with hypertension (-0.69% [-0.82 to -0.57]) and no hypertension (-0.66% [-0.80 to -0.52]). Saxagliptin was well tolerated, with similar adverse event rates and types compared with placebo. There was a < 1% rate of confirmed hypoglycemia in all groups except in patients with CV history who received placebo (2.1%). CONCLUSION: Saxagliptin improved glycemic measures, resulted in low rates of confirmed hypoglycemia, and was well tolerated in patients with or without CVD and CV risk factors.