Supplemental discussion, tables, and data for: Chronic semaglutide treatment in rats leads to daily excessive concentration-dependent sucrose intake

Abstract

In apparent contrast with studies investigating the effects of GLP-1 agonism on water intake, in our study, changes in water intake seem to closely follow changes in food intake during Escalation, Maintenance, and in Experiment 1 (and PD3 in Experiment 2), after treatment stopped. There is research showing effects of liraglutide on water intake independent of food intake. In that study, McKay and colleagues found that rats treated with vehicle reduced 24-h water intake by approximately 40% in the absence, compared with the presence, of food, whereas food availability did not influence water intake in Liraglutide-treated rats. We did not measure water intake in the absence of food and so we cannot say how this would have affected the outcome. However, in the experiments by McKay et al., animals received drug or vehicle only on testing occasions, which were separated by 3-4 days; this acute dosing likely better corresponds to our results during Escalation, when we did observe a decrease in water intake. Given the propensity for acute doses of GLP-1 analog drugs to sometimes induce malaise, it is possible that some of the decrease in water intake seen in our SEMA rats during dose escalation and in the liraglutide-treated rats in the McKay et. al. study may have been due to untoward side effects of the drugs. If malaise was the cause of reduced water intake, however, the return to BASE water intake by our SEMA rats during Maintenance suggests any ill effects of SEMA introduction and escalation resolved during dose maintenance.