SUN-606 Sglt2 Inhibition Has Negligible Effect On Long-term Appetite Regulation

Abstract Disclosure: J. Lee: None. S. Park: None. E. Kim: None. O. Kwon: None. E. Lee: None. Background: The effect of SGLT2 inhibitors (SGLT2i) on appetite and food intake remains unclear. This study investigated the effects of SGLT2i on appetite, food craving, and body weight in patients with type 2 diabetes and diabetic rodent models. Methods: Thirty-four participants were randomized to receive either dapagliflozin or sitagliptin for 24 weeks. The primary endpoint was body weight changes from baseline; secondary outcomes included food intake, appetite and related hormone changes, and glycemic control. Rodent studies involved OLETF rats treated with empagliflozin for 12 weeks and high-fat diet-based diabetic mice given a single intracerebroventricular injection of dapagliflozin to evaluate chronic and acute effects on food intake and appetite-related gene expression. Results: Weight reduction in the dapagliflozin group was lower than expected, with a 1.99 kg difference at 24 weeks (P < 0.001). Leptin levels significantly decreased in the dapagliflozin group, but food intake and appetite scores showed no differences between the groups. Consistent with the human study, food intake at 12 weeks of empagliflozin treatment in OLETF rats showed no difference from the controls, while increased intake during the first 3 weeks in the empagliflozin group was consistent with that during acute central treatment with dapagliflozin in diabetic mice. Conclusions: Sustained SGLT2i treatment does not cause compensatory appetite increase after weight stabilization. This finding suggests that less-than-expected weight loss with SGLT2i may result from mechanisms other than sustained changes in appetite or food intake. Presentation: Sunday, July 13, 2025