Differing Effect of the Sodium-Glucose Cotransporter 2 Inhibitor Ipragliflozin on the Decrease of Fat Mass vs. Lean Mass in Patients With or Without Metformin Therapy

BACKGROUND: We previously reported changes of body composition determined by dual-energy X-ray absorptiometry after treatment with ipragliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor. In that study, mean body weight was decreased by 3.5 kg (4.3% of the baseline value) after ipragliflozin treatment at 50 mg/day, with fat mass and lean mass showing similar reductions of 1.7 and 1.8 kg, respectively. A long-term decrease of lean mass in patients treated with SGLT2 inhibitors may be associated with loss of skeletal muscle, which could potentially have an impact on quality of life. METHODS: In this post hoc analysis, we investigated whether changes of body composition were influenced by other medications for diabetes in 20 patients (11 men and nine women) who received ipragliflozin for 24 weeks. RESULTS: When we divided the patients into two subgroups with or without metformin treatment, fat mass showed a significant decrease in the ipragliflozin + metformin subgroup and a significantly greater decrease compared to the ipragliflozin subgroup (2.0 kg; 95% confidence interval (CI): 0.1 - 3.9; P = 0.038). Lean mass was significantly decreased in the ipragliflozin subgroup, but the decrease showed no significant difference from that in the ipragliflozin + metformin subgroup (1.9 kg; 95% CI: -4.1 - 0.3; P = 0.087). No significant differences of body composition changes were observed with other antidiabetic agents. CONCLUSIONS: More desirable weight reduction due to preferential fat loss and less muscle loss may be achieved by combining an SGLT2 inhibitor with metformin.