SGLT2 Inhibitors Do Not Increase Appetite After Weight Stabilization: Study
Researchers have found in a new study that sustained treatment with SGLT2 inhibitors does not lead to a compensatory increase in appetite after body weight stabilizes. The therapy also does not significantly affect appetite-regulating hormones or molecules, supporting its metabolic safety regarding energy intake. These findings suggest that the smaller-than-expected weight loss seen with SGLT2 inhibitors is likely due to mechanisms other than increased appetite or food consumption. The study was published in the Journal of Korean Medical Science by Joonyub L. and colleagues.
The effects of long-term administration of the SGLT2 inhibitors on the pathway regulating appetite were studied systematically through a parallel translational approach involving both human and animal model studies. The human study involved randomization in a controlled study of 34 subjects who had type 2 diabetes, and were assigned either to dapagliflozin or sitagliptin, which are the SGLT2 and DPP-4 inhibitors respectively, for 24 weeks.
The main endpoint for the human study was body weight measured objectively, while other secondary objectives included food intake, appetite measurement scores, appetite-related hormones and glucose levels. On the animal study front, OLETF rats were used, and treated for 12 weeks with the SGLT2 inhibitor empagliflozin or control solution. Food intake and hypothalamic expression genes in the pathways related to appetite regulation were measured both acutely and chronically after initiation of treatment.
Key findings:
- After the 24-week clinical trial period, weight loss for the dapagliflozin group turned out to be less than what was theoretically predicted, resulting in only an insignificant amount of 1.99 kg below the initial value (P < 0.001).
- The concentration of systemic leptin, which is a satiating hormone secreted by adipocytes, dropped significantly for the group taking dapagliflozin owing to fat mass loss, although there were no statistically significant changes concerning actual food consumption and subjective appetite scores between the experimental groups after 24 weeks.
- In the rodent trial, rats administered empagliflozin experienced a temporary increase in food consumption specifically in the first 3 weeks.
- At the 12th week of constant administration of empagliflozin, there were no statistically significant differences in the daily food intake between the empagliflozin and control groups, similar to those of human trials.
This translational study demonstrates that there is no appetite compensation induced by chronic SGLT2 inhibitor administration after the achievement of weight stability, making the use of such drugs safe in terms of energy intake. This research gives invaluable medical recommendations to endocrinologists and general practitioners when working with diabetic patients. It is possible to safely give such medications without fearing that the drug will induce chronic overeating or excessive food desire.
Reference:
Lee, J., Park, S., Kim, E., Park, J.-Y., Rhee, M., Hughes, J. W., Ko, S.-H., Kwon, O., & Lee, E. Y. (2026). Limited impact of sodium-glucose cotransporter-2 inhibitors on appetite and body weight: Evidence from clinical and rodent studies. Journal of Korean Medical Science, 41(18), e44. https://doi.org/10.3346/jkms.2026.41.e44
