Table 1.
Summary of studies in patients with type 2 diabetes mellitus included in this review.
| Study and citation | Clinical trial registration number | Phase | Background therapy | Treatment groups (Na) | Study length | Primary end point (exploratory end point for extension study) | Adjusted mean change in HbA1c from baseline, % |
|---|---|---|---|---|---|---|---|
| Dedicated empagliflozin + metformin initial combination | |||||||
| Initial combination Hadjadj et al27 |
NCT01719003 | 3 | None | Empagliflozin 12.5 mg + metformin 1000 mg twice daily (n = 169) | 24 wk | Change in HbA1c from baseline at week 24 | −2.08 |
| Empagliflozin 12.5 mg + metformin 500 twice daily (n = 165) | −1.93 | ||||||
| Empagliflozin 5 mg + metformin 1000 twice daily (n = 167) | −2.07 | ||||||
| Empagliflozin 5 mg + metformin 500 mg twice daily (n = 161) | −1.98 | ||||||
| Empagliflozin 25 mg once daily (n = 164) | −1.36 | ||||||
| Empagliflozin 10 mg once daily (n = 169) | −1.35 | ||||||
| Metformin 1000 mg twice daily (n = 164) | −1.75 | ||||||
| Metformin 500 mg twice daily (n = 168) | −1.18 | ||||||
| Open-label empagliflozin 12.5 mg twice daily + metformin 1000 mg twice daily (n = 53) | (Not reported) | ||||||
| Empagliflozin added to stable metformin | |||||||
| Twice daily vs once daily Ross et al28 |
NCT01649297 | 2b | Metformin | Empagliflozin 5 mg twice daily (n = 219) | 16 wk | Change in HbA1c from baseline at week 16 | −0.66 |
| Empagliflozin 10 mg once daily (n = 220) | −0.64 | ||||||
| Empagliflozin 12.5 mg twice daily (n = 219) | −0.83 | ||||||
| Empagliflozin 25 mg once daily (n = 218) | −0.72 | ||||||
| Placebo (n = 107) | −0.22 | ||||||
| Dose ranging (study 1) Rosenstock et al33 |
NCT00749190 | 2 | Metformin | Empagliflozin 1 mg once daily (n = 71) | 12 wk | Change in HbA1c from baseline at week 12 | −0.09 |
| Empagliflozin 5 mg once daily (n = 71) | −0.23 | ||||||
| Empagliflozin 10 mg once daily (n = 71) | −0.56 | ||||||
| Empagliflozin 25 mg once daily (n = 70) | −0.55 | ||||||
| Empagliflozin 50 mg once daily (n = 70) | −0.49 | ||||||
| Placebo (n = 71) | +0.15 | ||||||
| Open-label sitagliptin 100 mg once daily (n = 71) | −0.45 | ||||||
| Treatment-naïve (study 2) Ferrannini et al32 |
NCT00789035 | 2b | None | Empagliflozin 5 mg once daily (n = 81) | 12 wk | Change in HbA1c from baseline at week 12 | −0.4 |
| Empagliflozin 10 mg once daily (n = 81) | −0.5 | ||||||
| Empagliflozin 25 mg once daily (n = 82) | −0.6 | ||||||
| Placebo (n = 82) | +0.1 | ||||||
| Open-label metformin (n = 80) | −0.7 | ||||||
| Ferrannini et al31 (open-label extension of study 1 and study 2) | NCT00881530 | None or metformin | Open-label extensionb | ||||
| Patients receiving empagliflozin 10 mg (n = 272; 166 as add-on to metformin) | 78 wk | (Included change from baseline of preceding study to week 78 of extension study in HbA1c) | −0.34 | ||||
| Patients receiving empagliflozin 25 mg (n = 275; 166 as add-on to metformin) | −0.63 | ||||||
| Patients receiving metformin comparator (n = 56) | −0.56 | ||||||
| Patients receiving sitagliptin comparator (n = 56) | −0.40 | ||||||
| EMPA-REG MET Häring et al30 |
NCT01159600 | 3 | Metformin | Empagliflozin 10 mg once daily (n = 217) | 24 wk | Change in HbA1c from baseline at week 24 | −0.70 |
| Empagliflozin 25 mg once daily (n = 213) | −0.77 | ||||||
| Placebo (n = 207) | −0.13 | ||||||
| Merker et al34 (double-blind extension, EMPA-REG EXTEND MET) | NCT01289990 | Metformin | Double-blind extension | ≥52-wk double-blind extension | (Included change from baseline to week 76 in HbA1c) | ||
| Empagliflozin 10 mg once daily (n = 173) | −0.7 | ||||||
| Empagliflozin 25 mg once daily (n = 152) | −0.8 | ||||||
| Placebo (n = 138) | −0.1 | ||||||
| EMPA-REG H2H-SU Ridderstråle et al29 |
NCT01167881 | 3 | Metformin | Empagliflozin 25 mg once daily (n = 765) | 104 wk | Change in HbA1c from baseline at weeks 52 and 104 | −0.73/−0.66 |
| Glimepiride 1-4 mg once daily (n = 780) | −0.66/−0.55 (At weeks 52/104) |
||||||
| Empagliflozin added to treatment backgrounds that could include metformin | |||||||
| EMPA-REG METSU Häring et al35 |
NCT01159600 | 3 | Metformin and sulfonylurea | Empagliflozin 10 mg once daily (n = 225) | 24 wk | Change in HbA1c from baseline at week 24 | −0.82 |
| Empagliflozin 25 mg once daily (n = 216) | −0.77 | ||||||
| Placebo (n = 225) | −0.17 | ||||||
| Häring et al40 (double-blind extension, EMPA-REG EXTEND METSU) | NCT01289990 | Metformin and sulfonylurea | Double-blind extension | ≥52-wk double-blind extension | (Included change from baseline to week 76 in HbA1c) | ||
| Empagliflozin 10 mg once daily (n = 163) | −0.7 | ||||||
| Empagliflozin 25 mg once daily (n = 165) | −0.7 | ||||||
| Placebo (n = 145) | 0.0 | ||||||
| Empagliflozin and linagliptin add-on to metformin DeFronzo et al36 |
NCT01422876 | 3 | Metformin | Empagliflozin 25 mg/linagliptin 5 mg (n = 134) | 52 wk | Change in HbA1c from baseline at week 24 | −1.19 |
| Empagliflozin 10 mg/linagliptin 5 mg (n = 135) | −1.08 | ||||||
| Empagliflozin 25 mg (n = 140) | −0.62 | ||||||
| Empagliflozin 10 mg (n = 137) | −0.66 | ||||||
| Linagliptin 5 mg (n = 128) | −0.70 | ||||||
| Linagliptin as add-on to empagliflozin and metformin Tinahones et al39 |
NCT01778049 | 3 | Empagliflozin 10 mg and metformin | Linagliptin 5 mg + placebo (n = 126) | 24 wk | Change in HbA1c from baseline at week 24 | −0.54 |
| Placebo (n = 128) | −0.20 | ||||||
| Empagliflozin 25 mg and metformin | Linagliptin 5 mg + placebo (n = 112) | −0.58 | |||||
| Placebo (n = 112) | −0.09 | ||||||
| Empagliflozin as add-on to linagliptin and metformin Søfteland et al41 |
NCT01734785 | 3 | Linagliptin 5 mg and metformin | Empagliflozin 10 mg (n = 112) | 24 wk | Change in HbA1c from baseline at week 24 | −0.66 |
| Empagliflozin 25 mg (n = 110) | −0.56 | ||||||
| Placebo (n = 110) | 0.14 | ||||||
| EMPA-REG PIO Kovacs et al38 |
NCT01289990 | 3 | Pioglitazone ± metformin | Empagliflozin 10 mg once daily (n = 165) | 24 wk | Change in HbA1c from baseline at week 24 | −0.59 |
| Empagliflozin 25 mg once daily (n = 168) | −0.72 | ||||||
| Placebo (n = 165) | −0.11 | ||||||
| Kovacs et al37 (double-blind extension, EMPA-REG EXTEND PIO) | NCT01210001 | Pioglitazone ± metformin | Double-blind extension | ≥52-wk double-blind extension | (Included change from week 76 in baseline to HbA1c) | ||
| Empagliflozin 10 mg once daily (n = 106) | −0.61 | ||||||
| Empagliflozin 25 mg once daily (n = 106) | −0.70 | ||||||
| Placebo (n = 93) | −0.01 | ||||||
| EMPA-REG BASAL Rosenstock et al42 |
NCT01011868 | 2b | Basal insulin ± metformin ± sulfonylurea | Empagliflozin 10 mg (n = 169) | 78 wk | Change in HbA1c from baseline at week 18 | −0.6 |
| Empagliflozin 25 mg (n = 155) | −0.7 | ||||||
| Placebo (n = 170) | 0.0 | ||||||
| EMPA-REG MDI Rosenstock et al43 |
NCT01306214 | 3 | MDI insulin ± metformin | Empagliflozin 10 mg (n = 188) | 52 wk | Change in HbA1c from baseline at week 18 | −0.94 |
| Empagliflozin 25 mg (n = 189) | −1.02 | ||||||
| Placebo (n = 188) | −0.50 | ||||||
Abbreviations: HbA1c, glycated hemoglobin; MDI, multiple daily injections.
a
Randomized and received treatment (these values might differ from the total randomized).
b
Patients receiving empagliflozin 1, 5, or 50 mg or placebo were re-randomized to receive empagliflozin 10 or 25 mg—included patients are those who received treatment in both the initial and extension trials.