The SGLT2 Inhibitor Tofogliflozin Reduces Weight in People with Type 2 Diabetes due to Fluid Loss Initially and to Lipolysis in Late

It is well recognized that sodium/glucose cotransporter 2 inhibitors (SGLT2i) are associated with weight loss in people with type 2 diabetes. However, the time-dependent associations of weight loss with the anthropometric and body fluid measurements and serum parameters during SGLT2i intervention remain unclear. Thus, we aimed to clarify weight loss-related factors, carefully focusing on the clinical process during the long-term intervention with a SGLT2i, tofogliflozin in people with type 2 diabetes. We analyzed data from 775 people with type 2 diabetes that participated in tofogliflozin phase 3 trials. Participants received tofogliflozin (20, or 40 mg; n = 235, and 540, respectively) orally once daily for 52 weeks. The correlation analysis was performed at week 4, 24 and 52. Baseline characteristics showed men (66 %), age (mean: 58 years), HbA1c (8.0 %), BMI (26 kg/m²) and eGFR (84 mL/min/1.73m²). Tofogliflozin significantly reduced body weight at week 4, 24 and 52 (mean: -1.4, -3.0 and -3.0 kg, respectively). At week 4, weight loss was negatively correlated with both the change in body fluid measures (hematocrit, RBC count, serum creatinine level, and uric acid level) and beta-hydroxybutyrate (BHB). At week 24, weight loss was positively correlated with anthropometric measurements (waist and hip circumferences) and hepatic enzymes levels, and negatively correlated with adiponectin, HDL-C, and BHB levels, but not with body fluid measures. Although the values at week 52 were in concert with the results at week 24, there was a modest but significant correlation between weight loss and BHB level. Our results clarified that tofogliflozin reduces weight, especially that of visceral fat in people with type 2 diabetes, at least due to fluid loss initially and to lipolysis in late. Weight loss might contribute to decrease in the hepatic enzymes, whereas it also accompanies an increase in beta-hydroxybutyrate, the safety issue of which to be investigated in future.