Effects of HbA1c and weight reduction on blood pressure in patients with type 2 diabetes mellitus treated with exenatide

Aim: Treatment of patients with type 2 diabetes with glucagon-like peptide-1 (GLP-1) receptor agonist exenatide has showed improvements in glycaemic control coupled with weight loss and lowered blood pressure (BP). We examined the synergy between improved glycaemia and weight loss on BP reduction in patients treated with either exenatide twice daily (BID) or once weekly (QW). Methods: Combining data from three controlled trials, 686 (53% male) patients [baseline mean +/- SD: age 55 +/- 10 years, weight 95 +/- 20 kg, systolic blood pressure (SBP)/diastolic blood pressure (DBP) 130/79 +/- 15/9 mmHg, HbA1c 8.3 +/- 1.1%] treated with exenatide QW (n = 541) or BID (n = 145) were observed over 26 weeks. Using weighted means (WMs) of the longitudinal measures of HbA1c and weight, patients were subdivided into four groups at each visit by glycaemic and weight responses; patients who failed to reduce both HbA1c and weight below WMs became the reference group (R). The other three groups corresponded to patients with HbA1c reduction (A), weight reduction (W) and both HbA1c and weight reduction (AW). Results: Compared with R, patients in AW, A and W groups had a significantly higher likelihood of improving SBP <130 mmHg by 88, 30 and 61%, respectively. Compared with R, patients in AW, A and W had 63, 13 and 45% higher likelihood of improving DBP <80 mmHg. Conclusion: Although the mechanism of BP-lowering effect of exenatide is not established, it appears that the short-term dynamics of BP is related to concomitant effects on glycaemia and body weight. These data offer a preliminary insight into the possible cardiometabolic effects of GLP-1 receptor agonism.