Bromocriptine - A novel approach to the treatment of type 2 diabetes

OBJECTIVE - In vertebrates, body fat stores and insulin action are controll ed by the temporal interaction of circadian neuroendocrine oscillations. Br omocriptine modulates neurotransmitter action in the brain and has been sho wn to improve glucose tolerance and insulin resistance in animal models of obesity and diabetes. We studied the effect of a quick-release bromocriptin e formulation on glucose homeostasis and insulin sensitivity in obese type 2 diabetic subjects. RESEARCH DESIGN AND METHODS - There were 22 obese subjects with type 2 diab etes randomized to receive a quick-release formulation of bromocriptine (n = 15) or placebo (n = 7) in a 16-week double-blind study. Subjects were pre scribed a weight-maintaining diet to exclude any effect of changes in body weight on the primary outcome measurements. Fasting plasma glucose concentr ation and HbA(1c) were measured at 2- to 4-week intervals during treatment. Body composition (underwater weighing), body fat distribution (magnetic re sonance imaging), oral glucose tolerance (oral glucose tolerance test [OGTT ]), insulin-mediated glucose disposal, and endogenous glucose production (2 -step euglycemic insulin clamp, 40 and 160 mU . min(-1) . m(-2)) were measu red before and after treatment. RESULTS - No changes in body weight or body composition occurred during the study in either placebo- or bromocriptine-treated subjects. Bromocriptine significantly reduced HbA(1c) (from 8.7 to 8.1%, P = 0.009) and Easting pla sma glucose (from 190 to 172 mg/dl, P = 0.02) levels, whereas these variabl es increased during placebo treatment (from 8.5 to 9.1%, NS, and from 187 t o 223 mg/dl, P = 0.02, respectively). The differences in HbA(1c) (Delta = 1 .2%, P = 0.01) and fasting glucose (Delta = 54 mg/dl, P < 0.001) levels bet ween the bromocriptine and placebo group at 16 weeks were highly significan t. The mean plasma glucose concentration during OGTT was significantly redu ced by bromocriptine (from 294 to 272 mg/dl, P = 0.005), whereas it increas ed in the placebo group. No change in glucose disposal occurred during the first step of the insulin clamp in either the bromocriptine- or placebo-tre ated group. During the second insulin clamp step, bromocriptine improved to tal glucose disposal from 6.8 to 8.4 . mg min(-1) . kg(-1) Eat-free mass (F FM) (P = 0.01) and nonoxidative glucose disposal from 3.3 to 4.3 mg . min(- 1) kg(-1) FFM (P < 0.05), whereas both of these variables deteriorated sign ificantly (P less than or equal to 0.02) in the placebo group. CONCLUSIONS - Bromocriptine improves glycemic control and glucose tolerance in obese type 2 diabetic patients. Both reductions in fasting and postpran dial plasma glucose levels appear to contribute to the improvement in gluco se tolerance. The bromocriptine-induced improvement in glycemic control is associated with enhanced maximally stimulated insulin-mediated glucose disp osal.