Lack of effects of the β₃-adrenoreceptor agonist UL-TG 307 on insulin sensitivity and insulin secretion in Type 2 diabetic patients

Summary

The effects of a novel β₃-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 hyperinsul-inaemic 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 (Si): UL-TG 307 2.5 ± 0.6 (mean ± SD) vs. placebo 2.2 ± 0.8 ml/min^*m² per μU/ml) nor increased insulin secretion (area under the serum insulin profile AUC_0-240/plasma glucose AUC_0-240: UL-TG 307 8.8 ± 7.4 vs. placebo 8.3 ± 6.4 μU/ml/mmol/l). No differences in lipid metabolism, metabolic control, and body weight were observed. We conclude that two weeks' administration of the β₃-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.

Key words

β₃-Adrenoreceptor agonist - insulin sensitivity - insulin secretion - Type 2 diabetes