Chronically elevated sympathetic nervous system (SNS) activity increases hepatic triglyceride (TG) synthesis and secretion and adipose free fatty acid mobilization leading to further hepatic TG synthesis and HTG. HTG often occurs in the presence of hypertension and this can be a biomarker of chronically elevated SNS activity. BQR, a dopamine agonist, is the only sympatholytic antidiabetes agent approved for T2D. Preclinical studies have repeatedly demonstrated that circadian-timed bromocriptine therapy ameliorates HTG. This study evaluated if circadian-timed BQR (1.6-4.8 mg/day) reduces HTG in a population of hypertensive HTG T2D subjects. Hypertensive HTG T2D subjects from the Cycloset Safety Trial (HbA1c ≥ 7.0) treated at baseline with diet +/- any one or two antidiabetes agents of sulfonylurea, metformin, thiazolidinedione or insulin (N = 378) and randomized to BQR or placebo for 24 weeks were analyzed for between group difference in change from baseline fasting plasma TG level. After 24 weeks of therapy, BQR significantly reduced fasting TG levels by between 34 to 219 mg/dl (13 to 36%) and HbA1c from -0.4 to -1.2 as the baseline fasting TG level rose from ≥ 150 to ≥ 400 mg/dl (Figure). These TG effects were even more pronounced in such subjects with elevated resting heart rate. Circadian-timed BQR reduces hypertriglyceridemia in T2D and this effect increases with increasing fasting TG level.
B. Chamarthi: Employee; Self; VeroScience LLC. M. Ezrokhi: Employee; Self; VeroScience LLC. A.H. Cincotta: Employee; Self; VeroScience LLC.