Differential Effects of SGLT-2 Inhibitors on Liver Function and Nocturia in Patients with Type 2 Diabetes: A Randomized Controlled Trial.

Purpose: This study investigated whether sodium-glucose cotransporter-2 inhibitors (SGLT-2is) improve liver function as a class effect and evaluated their effect on nocturia in patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: A total of 135 patients with type 2 diabetes and MASLD were randomly assigned to receive tofogliflozin (20 mg/day), dapagliflozin (5 mg/day), or empagliflozin (10 mg/day). Primary outcomes included changes in liver function and fibrosis markers-various transferases, fibrosis-4 index, mac-2 binding protein glycan isomer, and shear wave speed-along with nocturia frequency. Secondary outcomes were glycemic control, body weight, and lipid profiles. Patients were followed for seven months.

Results: The participants had a mean age of 61 years; 43% were female, HbA1c level was 8.7%, and the frequency of nocturia was 0.6 times. All three SGLT-2is significantly improved liver function markers, with no differences between groups. However, nocturia frequency significantly increased with empagliflozin (1.7 times) and dapagliflozin (1.9 times; both p < 0.001) but not with tofogliflozin (0.8 times; p = 0.503). Tofogliflozin resulted in a significantly smaller nocturia increase than the other two drugs (p < 0.001). However, this significant difference persisted up to 1 month; from 3 months onward, urinary frequency improved in all groups, and the difference was not observed. Glycemic control, body weight, and lipid profiles improved similarly across all groups.

Conclusion: SGLT-2is improve liver function as a class effect, but their impact on nocturia frequency differs. Tofogliflozin, likely due to its shorter half-life, has the most favorable nocturia profile and may be preferable for patients at risk. The UMIN Clinical Trial Registry number for this study is UMIN000054278; Clinical Trials Registry date 28/04/2024.