Background and aims: We investigated the effect of WAY-163909, a novel 5-hydroxytryptamine selective 2C receptor agonist on body weight, blood glucose levels, and insulin resistance in obese and diabetic Wistar rats. Materials and methods: We used twenty male Wistar rats with obesity and obesity-induced diabetes and twenty healthy Wistar rats as a control group. Each of these groups was separated into two subgroups: one with a daily intraperitoneal application of WAY-163909 (1 mg/kg) and one without. During the study, body weight, blood glucose levels, and immunoreactive insulin were tracked. Results: A reduction of 5.5% (p < 0.05) in body weight was registered in the rat group with diabetes and obesity and 2.56% in the control group with a daily application of WAY-163909 (1 mg/kg) at the end of the study. Decreases of 35.4% in blood glucose levels at week four in the diabetic and obese rat group with a daily application of WAY-163909 (1 mg/kg) were registered. A reduction of insulin levels of 4.1% (p < 0.05) in the diabetic and obese rats group using WAY-163909 was also observed. Conclusion: In our study, using WAY-163909 (1 mg/kg) led to a reduction of blood glucose levels, immunoreactive insulin, and body weight.

Many regulatory pathways for food intake, including those that use serotonin as a neurotransmitter, are affected by obesity or by hypercaloric diets leading to obesity. Summarizing the data known so far, it can be said that reduced serotonergic signalling and low availability of SERT are associated with hyperphagia and obesity. Because of these facts, it is important to know how serotonin mediation in the brain works and how it affects eating behaviour and glucose metabolism. Ro60-0175 is a selective serotonin agonist in the central nervous system that we use in our study. Forty Wistar rats were separated into two groups – rats with obesity and diabetes and healthy rats (control group). Each of these groups was separated into other two – one with a daily intraperitoneal injection (i.p.) of Ro60-0175 (3 mg/kg) and one without. For four weeks, we were tracking blood glucose levels, insulin secretion and rats' weight. It was shown that after the application of Ro60-0175, the weight of the rats in the diabetic and obese group decreased by 5.5% (p<0.05), and by 2.56% in the control group, and there was no significant change in the groups without daily intraperitoneal injection of Ro60-0175. In the diabetic and obese rats group in which Ro60-0175 was applied, we registered a reduction of hyperglycemia by 35.4% (p<0.05) comparing the results before the start of using Ro60-0175, which is greater in the rats which lost more body weight. The research also shows decreasing of insulin resistance by 42.1% (p<0.01) in diabetic and obese rats group using Ro60-0175. Using Ro60-0175 for treatment of obesity and obesity-induced diabetes in male Wistar rats, leads to significant reduction of body weight and hyperglycemia and peripheral insulin resistance.