Lack of effects of the beta3-adrenoreceptor agonist UL-TG 307 on insulin sensitivity and insulin secretion in Type 2 diabetic patients.

The effects of a novel beta3-adrenoreceptor agonist, UL-TG 307, on insulin sensitivity and insulin secretion, lipid metabolism, and body weight were investigated. Thirteen diet treated male Type 2 diabetic patients participated in a randomized, double-blind, placebo controlled cross-over trial with two 14 day administration periods with placebo and UL-TG 307 (24 mg daily). After each administration period insulin secretion was assessed by means of an OGTT and insulin sensitivity was measured by an hyperinsulinaemic euglycaemic glucose clamp. Lipid metabolism was evaluated by measuring non-esterified fatty acid, glycerol, and triglyceride serum concentrations at the end of each administration period. Treatment with UL-TG 307 did not improve insulin sensitivity (insulin sensitivity index (S(I)): UL-TG 307 2.5 -/+ 0.6 (mean +/- SD) vs. placebo 2.2 +/- 0.8 ml/min*m2 per microU/ml) nor increased insulin secretion (area under the serum insulin profile AUC0-240/plasma glucose AUC0-240: UL-TG 307 8.8 +/- 7.4 vs. placebo 8.3 +/- 6.4 microU/ ml/mmol/l). No differences in lipid metabolism, metabolic control, and body weight were observed. We conclude that two weeks' administration of the beta3-adrenoreceptor agonist UL-TG 307 in a daily dose of 24 mg did not lead to any significant effect in diet treated type 2 diabetic patients.