Aims. The present study is aimed at exploring the effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on weight in type 2 diabetes mellitus (T2DM) and therapeutic regimen recommendations. Methods. 20,019 patients with T2DM were enrolled. The maximal effect ( E max ) models, whose evaluation index was change rate of body weight from baseline value, were used to analyze data using nonlinear mixed effect modeling (NONMEM). Results. For SGLT-2 inhibitors, canagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin and tofogliflozin, the E max , and treatment duration to reach half of the maximal effects (ET50) were -3.72% and 3.35 weeks, -5.59% and 16.8 weeks, -2.84% and 3.42 weeks, -3.43% and 3.09 weeks, -3.04% and 4.38 weeks, and -2.45% and 3.16 weeks, respectively. In addition, for T2DM patients, 100 mg/day canagliflozin needs to be taken 13.4 weeks for the plateau of effect on weight; 10 mg/day empagliflozin needs to be taken 67.2 weeks for the plateau of effect on weight; 5 mg/day ertugliflozin needs to be taken 13.68 weeks for the plateau of effect on weight; 50 mg/day ipragliflozin needs to be taken 12.36 weeks for the plateau of effect on weight; 2.5 mg/day luseogliflozin needs to be taken 17.52 weeks for the plateau of effect on weight; 20 mg/day tofogliflozin needs to be taken 12.64 weeks for the plateau of effect on weight. Conclusions. This was the first study to explore effects of SGLT-2 inhibitors on weight in T2DM; meanwhile, the optimum dosages and treatment durations on weight from canagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, and tofogliflozin were recommended, respectively.

Objectives. The purpose of this study was to explore the effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on urine albumin to creatinine ratio (UACR) in type 2 diabetes mellitus (T2DM) patients and to recommend appropriate medication care scheme. Methods. 8371 T2DM patients from four dapagliflozin studies and two canagliflozin studies were collected for analyzing with nonlinear mixed effect model (NONMEM). The change rates of UACR from baseline were intended to be evaluation indicators. Results. In the present study, there was no significant difference in the effects on UACR using dapagliflozin or canagliflozin treatment in T2DM patients. The maximal effect ( E max ) and the treatment duration of reaching half of E max (ET50) from SGLT-2 inhibitors on UACR in T2DM patients were -19.2% and 0.448 weeks, respectively. Further, the treatment duration to reach 25%, 50%, 75%, and 80% E max was 0.150 weeks, 0.448 weeks, 1.344 weeks, and 1.792 weeks, respectively. Namely, for achieving the plateau period (80% of E max ) of SGLT-2 inhibitors on UACR in T2DM patients, 10 mg/day dapagliflozin (or 100 mg/day canagliflozin) should be taken for at least 1.792 weeks. Conclusions. To our knowledge, the present study explored the effects of SGLT-2 inhibitors on UACR in T2DM patients, meanwhile, recommended appropriate medication care scheme for the first time.