A Review of Exenatide: Optimizing Glycemic Control and Associated Cardiovascular Risk Factors in Type 2 Diabetes
BACKGROUND The majority of patients with type 2 diabetes mellitus have blood pressure (BP) exceeding the recommended value of <130/80 mm Hg. Optimal control of hyperglycemia and hypertension has been shown to reduce the incidence of macrovascular and microvascular complications due to diabetes. Treatment with the GLP-1 receptor agonist exenatide, previously demonstrated to reduce hemoglobin A(1C) and weight in subjects with type 2 diabetes, was associated with BP reduction in several studies. METHODS This analysis explored the effects of exenatide vs. placebo or insulin on BP measurements in pooled data from six trials including 2,171 subjects studied for at least 6 months. RESULTS Overall, 6 months of exenatide treatment was associated with a significantly greater reduction in systolic BP (SBP) compared with placebo (least squares mean (s.e.): difference of -2.8 mm Hg (0.75); P = 0.0002) or insulin (difference of -3.7 mm Hg (0.85); P < 0.0001). No significant intergroup differences in diastolic BP (DBP) were observed. The majority of the intergroup difference was observed in subjects with SBP > or = 130 mm Hg (difference of -3.8 mm Hg (1.08) from placebo: P = 0.0004; difference of -4.0 mm Hg (1.01) from insulin; P < 0.0001). The largest intertreatment differences between exenatide and comparators were observed in subjects with SBP >/=150 mm Hg. Similar responses were observed in African-American subjects. A weak correlation between the amount of weight lost and reduction in SBP was found (r = 0.09, P = 0.002) for exenatide-treated subjects. CONCLUSIONS These results support the need for a prospective, randomized, controlled study of BP changes during exenatide treatment in patients with hypertension and type 2 diabetes.