Lack of effects of the beta(3)-adrenoreceptor agonist UL-TG 307 on insulinsensitivity and insulin secretion in Type 2 diabetic patients

The effects of a novel beta(3)-adrenoreceptor agonist, UL-TG 307, on insuli n sensitivity and insulin secretion, lipid metabolism, and body weight were investigated. Thirteen diet treated male Type 2 diabetic patients particip ated in a randomized, double-blind, placebo controlled cross-over trial wit h 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 eu glycaemic glucose clamp. Lipid metabolism was evaluated by measuring non-es terified fatty acid, glycerol, and triglyceride serum concentrations at the end of each administration period. Treatment with UL-TG 307 did not improv e insulin sensitivity (insulin sensitivity index (S-I): UL-TG 307 2.5 +/- 0 .6 (mean +/- SD) vs, placebo 2.2 +/- 0.8 ml/min*m(2) per mu U/ml) nor incre ased insulin secretion (area under the serum insulin profile AUC(0-240)/pla sma glucose AUC(0-240): UL-TG 307 8.8 +/- 7.4 vs. placebo 8.3 +/- 6.4 mu U/ ml/mmol/l). No differences in lipid metabolism, metabolic control, and beer y weight were observed. We conclude that two weeks' administration of the b eta(3)-adrenoreceptor agonist UL-TG 307 in a daily dose of 24 mg did not le ad to any significant effect in diet treated type 2 diabetic patients.