Circadian‐timed quick‐release bromocriptine lowers elevated resting heart rate in patients with type 2 diabetes mellitus

OBJECTIVE: Sympathetic nervous system (SNS) overactivity is a risk factor for insulin resistance and cardiovascular disease (CVD). We evaluated the impact of bromocriptine‐QR, a dopamine‐agonist antidiabetes medication, on elevated resting heart rate (RHR) (a marker of SNS overactivity in metabolic syndrome), blood pressure (BP) and the relationship between bromocriptine‐QR's effects on RHR and HbA1c in type 2 diabetes subjects. DESIGN AND SUBJECTS: RHR and BP changes were evaluated in this post hoc analysis of data from a randomized controlled trial in 1014 type 2 diabetes subjects randomized to bromocriptine‐QR vs placebo added to standard therapy (diet ± ≤2 oral antidiabetes medications) for 24 weeks without concomitant antihypertensive or antidiabetes medication changes, stratified by baseline RHR (bRHR). RESULTS: In subjects with bRHR ≥70 beats/min, bromocriptine‐QR vs placebo reduced RHR by −3.4 beats/min and reduced BP (baseline 130/79; systolic, diastolic, mean arterial BP reductions [mm Hg]: −3.6 [P = .02], −1.9 [P = .05], −2.5 [P = .02]). RHR reductions increased with higher baseline HbA1c (bHbA1c) (−2.7 [P = .03], −5 [P = .002], −6.1 [P = .002] with bHbA1c ≤7, >7, ≥7.5%, respectively] in the bRHR ≥70 group and more so with bRHR ≥80 (−4.5 [P = .07], −7.8 [P = .015], −9.9 [P = .005]). Subjects with bRHR <70 had no significant change in RHR or BP. With bHbA1c ≥7.5%, %HbA1c reductions with bromocriptine‐QR vs placebo were −0.50 (P = .04), −0.73 (P = .005) and −1.22 (P = .008) with bRHR <70, ≥70 and ≥80, respectively. With bRHR ≥70, the magnitude of bromocriptine‐QR‐induced RHR reduction was an independent predictor of bromocriptine‐QR's HbA1c lowering effect. CONCLUSION: Bromocriptine‐QR lowers elevated RHR with concurrent decrease in BP and hyperglycaemia. These findings suggest a potential sympatholytic mechanism contributing to bromocriptine‐QR's antidiabetes effect and potentially its previously demonstrated effect to reduce CVD events.