In a specific strain of rats with diabetes, a 7-day course of an SGLT2 inhibitor raises the amount of glucose produced by the liver during fasting by about 30% and lowers the amount of glucose used...

We analyzed one assertion about SGLT2 inhibitors in Zucker diabetic fatty rats and found it supports the idea that these drugs increase endogenous glucose production and reduce glucose disposal. Specifically, in this strain of rats, a 7-day course of an SGLT2 inhibitor was linked to a roughly 30% rise in liver glucose output during fasting and a 40% drop in how much glucose the body used overall [1]. These changes resemble metabolic patterns seen during fasting or lower calorie intake. What we’ve found so far is limited to this single observation in one type of rat model. There are no studies in our review that contradict this finding, but we also don’t have data from other rat strains, different doses, longer treatment periods, or comparisons to other diabetes medications. The term “endogenous glucose production” refers to glucose made inside the body — mostly by the liver — rather than from food. “Glucose disposal” means how much glucose the body takes up and uses, mainly by muscles and fat tissue. We cannot say whether this happens in humans, or if it’s a temporary effect, or how it might interact with other treatments. The evidence we’ve reviewed so far leans toward this pattern occurring in Zucker diabetic fatty rats under these specific conditions, but we don’t yet know why it happens or what it means for long-term health. In everyday terms: In this one type of diabetic rat, the drug seems to make the liver pump out more sugar while the body uses less of it — similar to what happens when you eat less. But we don’t know yet if this is helpful, harmful, or just a short-term side effect.