Diazoxide has been tested in a number of obese and obese diabetic animal models. Most of the models involve strains that are genetically predisposed to obesity and diabetes including the Zucker Fatty rat, the Zucker Fatty Diabetic rat, the Otsuka Long Evans Takashima Fatty rat, and the diet induced obese mouse. In every model, use of diazoxide reduced weight gain, prevented accumulation of excess body fat and delayed or prevented the progression to diabetes. The response to treatment in animal models can best be exemplified by the results of Alemzadeh et al. [Metabolism Clinical and Experimental 2008; 57:1597–1607] in Zucker fatty rats, an animal model which is hyperphagic due to a mutation in the leptin receptor rendering it resistant to leptin. In this study, Zucker fatty rats were treated for 4 weeks with diazoxide starting at age 7 weeks. Based on the mode of action, there would are expected to be 4 key impacts of diazoxide treatment in this model, reduced food intake (i.e. reduced hyperphagia), reduced weight gain, increased β-oxidation of fat and reduced circulating triglycerides. These impacts were all statistically significant. Basal metabolic rate (similar to resting energy expenditure) was also increased in these animals.
Impact of diazoxide on hyperphagia, weight gain, beta-oxidation of fat and circulating triglycerides in the Zucker Fatty Rat