Aim: To assess the efficacy and safety of ipragliflozin as add-on therapy to metformin in Russian patients with T2DM.
Methods: In this double-blind trial conducted in 14 centers in Russia, 165 patients were randomized 2:1 to ipragliflozin (50 mg/day) or placebo for 24 weeks while continuing metformin. Patients who had HbA1c ≥7.0% at Week 12 received open-label ipragliflozin (50 mg/day) in addition to the blinded drug from Week 12-24.
Results: Significant reductions in HbA1c and body weight from baseline to Week 12 in favor of ipragliflozin were observed; the incidence of AEs was similar in both groups (Table). HbA1c and weight improvements were sustained from Week 12-24 in patients who remained on 50 mg ipragliflozin (mean change from Week 12: 0.16% and -0.48 kg, respectively; p>0.05). Uptitration to 100 mg ipragliflozin led to a further reduction in body weight (mean change from Week 12: -0.65 kg, P=0.004) and an additional 13% (9/69) achieving HbA1c <7% at Week 24. Incidence of AEs was similar in 50 mg (23.7%) and 100 mg groups (24.6%). No clinically significant changes in vital signs were noted during the study.
Conclusion: 50 mg Ipragliflozin added to metformin significantly reduced HbA1c and body weight after 12 weeks and showed a comparable safety profile as placebo. Uptitration to 100 mg/day conferred added benefits with no additional safety concerns.
Table. Efficacy and AE results from baseline to Week 12
| Baseline Iprag/Placebo | EOT Week 12 Iprag/Placebo | Change Iprag/Placebo | *Adjusted mean difference to placebo (95% CI) | *P value | ||
| Efficacy endpoints (FAS) | HbA1c, % | 8.40 (0.94)/8.46 (0.96) | 7.38 (0.90)/7.69 (1.11) | -1.01 (0.85)/-0.77 (1.10) | -0.26 (-0.53, 0.00) | 0.048 |
| Body weight, kg | 92.88 (16.25)/89.54 (15.60) | 90.87 (16.42)/88.92 (14.89) | -2.01 (2.47)/-0.62 (2.14) | -1.34 (-2.06, -0.61) | <0.001 | |
| Safety endpoints (SAF) | AEs, n (%) | - | 32 (29.1)/19 (34.5) | - | - | - |
| Drug-related AEs, n (%) | - | 12 (10.9)/4 (7.3) | - | - | - |
| Baseline Iprag/Placebo | EOT Week 12 Iprag/Placebo | Change Iprag/Placebo | *Adjusted mean difference to placebo (95% CI) | *P value | ||
| Efficacy endpoints (FAS) | HbA1c, % | 8.40 (0.94)/8.46 (0.96) | 7.38 (0.90)/7.69 (1.11) | -1.01 (0.85)/-0.77 (1.10) | -0.26 (-0.53, 0.00) | 0.048 |
| Body weight, kg | 92.88 (16.25)/89.54 (15.60) | 90.87 (16.42)/88.92 (14.89) | -2.01 (2.47)/-0.62 (2.14) | -1.34 (-2.06, -0.61) | <0.001 | |
| Safety endpoints (SAF) | AEs, n (%) | - | 32 (29.1)/19 (34.5) | - | - | - |
| Drug-related AEs, n (%) | - | 12 (10.9)/4 (7.3) | - | - | - |
*ANCOVA model with treatment as fixed effect, center as random effect, and baseline value as covariate. Data are presented as mean (SD) unless stated otherwise. Ipragliflozin (FAS = 109; SAF = 110) and placebo (FAS or SAF = 55). AEs, adverse events; EOT, end of treatment; FAS, full analysis set; Iprag, ipragliflozin; SAF, safety analysis set.
M.V. Shestakova: None. J.P. Wilding: Other Relationship; Self; Astellas, AstraZeneca, Boehringer Ingelheim GmbH, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi, Eli Lilly and Company, Orexigen Therapeutics, Inc., Merck & Co., Inc. W. Wilpshaar: Employee; Self; Astellas. R.N. Tretter: Employee; Self; Astellas Pharma Europe B.V.. V.L. Orlova: None. A.F. Verbovoy: None.
