Introduction
Methods
Study Design
Patient Population
Efficacy Assessments
Safety Assessments
Statistical Analyses
Post-Hoc Analyses
Results
Patient Disposition and Baseline Characteristics
Placebo (n = 154) | Ertugliflozin 5 mg (n = 158) | Ertugliflozin 15 mg (n = 155) | Total (n = 467) | |
---|---|---|---|---|
Age, years | 67.5 (8.9) | 66.7 (8.3) | 67.5 (8.5) | 67.3 (8.6) |
Male, n (%) | 72 (46.8) | 84 (53.2) | 75 (48.4) | 231 (49.5) |
Race, n (%) | ||||
White | 134 (87.0) | 127 (80.4) | 119 (76.8) | 380 (81.4) |
Asian | 9 (5.8) | 16 (10.1) | 20 (12.9) | 45 (9.6) |
Black or African American | 4 (2.6) | 6 (3.8) | 9 (5.8) | 19 (4.1) |
American Indian or Alaska Native | 1 (0.6) | 0 (0) | 0 (0) | 1 (0.2) |
Multiple | 6 (3.9) | 9 (5.7) | 7 (4.5) | 22 (4.7) |
Ethnicity, n (%) | ||||
Hispanic or Latino | 27 (17.5) | 29 (18.4) | 31 (20.0) | 87 (18.6) |
Region, n (%) | ||||
North America | 41 (26.6) | 55 (34.8) | 38 (24.5) | 134 (28.7) |
South America | 17 (11.0) | 17 (10.8) | 20 (12.9) | 54 (11.6) |
Europe | 70 (45.5) | 54 (34.2) | 62 (40.0) | 186 (39.8) |
Asia | 23 (14.9) | 24 (15.2) | 33 (21.3) | 80 (17.1) |
South Africa | 3 (1.9) | 8 (5.1) | 2 (1.3) | 13 (2.8) |
Duration of T2DM, years | 13.1 (8.1) | 14.9 (9.0) | 14.5 (8.5) | 14.2 (8.5) |
Body weight, kg | 90.4 (18.9) | 89.4 (22.5) | 85.8 (17.4) | 88.5 (19.8) |
BMI, kg/m2
| 33.2 (6.1) | 32.6 (6.8) | 31.7 (5.3) | 32.5 (6.1) |
A1C, % | 8.1 (0.9) | 8.2 (1.0) | 8.2 (0.9) | 8.2 (0.9) |
FPG, mg/dL | 156.9 (56.4) | 160.9 (56.4) | 157.5 (47.8) | 158.5 (53.6) |
eGFR, mL/min/1.73 m2
| 46.0 (9.4) | 46.8 (7.8) | 46.9 (9.1) | 46.6 (8.8) |
Medical history of CV disease or heart failure, n (%) | 76 (49.4) | 79 (50.0) | 77 (49.7) | 232 (49.7) |
Background AHA therapy at screening, n (%) | ||||
Currently on AHA therapy | 151 (98.1) | 153 (96.8) | 148 (95.5) | 452 (96.8) |
Biguanides | 36 (23.4) | 41 (25.9) | 38 (24.5) | 115 (24.6) |
DPP-4 inhibitors | 21 (13.6) | 22 (13.9) | 20 (12.9) | 63 (13.5) |
GLP-1 receptor agonists | 7 (4.5) | 3 (1.9) | 3 (1.9) | 13 (2.8) |
Insulins and analogs | 85 (55.2) | 89 (56.3) | 87 (56.1) | 261 (55.9) |
Sulfonylureas | 63 (40.9) | 65 (41.1) | 60 (38.7) | 188 (40.3) |
Others | 8 (5.2) | 8 (5.1) | 9 (5.8) | 25 (5.4) |
Efficacy
A1C
Week 26 | |||
---|---|---|---|
Placebo | Ertugliflozin 5 mg | Ertugliflozin 15 mg | |
Overall cohort (primary analysis) | |||
n = 154 |
n = 158 |
n = 155 | |
LS mean (95% CI) | – 0.3 (– 0.4, – 0.1) | – 0.3 (– 0.4, – 0.1) | – 0.4 (– 0.6, – 0.3) |
Difference in LS means (95% CI) versus placebo | – | – 0.0 (– 0.2, 0.2) | – 0.2 (– 0.4, 0.1) |
P value | – | 0.807b
| 0.155 |
Stage 3A CKD cohort (secondary analysis) | |||
n = 99 |
n = 105 |
n = 97 | |
LS mean (95% CI) | – 0.3 (– 0.5, – 0.1) | – 0.3 (– 0.5, – 0.1) | – 0.4 (– 0.6, – 0.2) |
Difference in LS means (95% CI) versus placebo | – | – 0.0 (– 0.3, 0.2) | – 0.1 (– 0.4, 0.2) |
P valueb
| – | 0.828 | 0.496 |
Overall cohort (post hoc analysis excluding metformin users) | |||
n = 128 |
n = 134 |
n = 127 | |
LS mean (95% CI) | – 0.1 (– 0.3, 0.0) | – 0.3 (– 0.4, – 0.1) | – 0.5 (– 0.6, – 0.3) |
Difference in LS means (95% CI) versus placebo | – | – 0.1 (– 0.4, 0.1) | – 0.3 (– 0.6, – 0.1) |
Stage 3A CKD cohort (post hoc analysis excluding metformin users) | |||
n = 79 |
n = 89 |
n = 75 | |
LS mean (95% CI) | – 0.1 (– 0.3, 0.1) | – 0.3 (– 0.5, – 0.1) | – 0.4 (– 0.7, – 0.2) |
Difference in LS means (95% CI) versus placebo | – | – 0.2 (– 0.5, 0.1) | – 0.4 (– 0.6, – 0.1) |
Week 52a
| |||
---|---|---|---|
Placebo | Ertugliflozin 5 mg | Ertugliflozin 15 mg | |
Stage 3A CKD cohort (secondary analysis) | |||
n = 99 |
n = 105 |
n = 97 | |
LS mean (95% CI) | – 0.3 (– 0.5, – 0.0) | – 0.2 (– 0.5, – 0.0) | – 0.4 (– 0.6, – 0.2) |
Difference in LS means (95% CI) versus placebo | – | 0.0 (– 0.3, 0.3) | – 0.1 (– 0.4, 0.2) |
Stage 3A CKD cohort (post hoc analysis excluding metformin users) | |||
n = 79 |
n = 89 |
n = 75 | |
LS mean (95% CI) | 0.0 (– 0.3, 0.3) | – 0.2 (– 0.5, 0.1) | – 0.4 (– 0.6, – 0.1) |
Difference in LS means (95% CI) versus placebo | – | – 0.2 (– 0.6, 0.2) | – 0.4 (– 0.8, 0.0) |
Week 26 | Week 52 | |||||
---|---|---|---|---|---|---|
Placebo (n = 99) | Ertugliflozin 5 mg (n = 105) | Ertugliflozin 15 mg (n = 97) | Placebo (n = 99) | Ertugliflozin 5 mg (n = 105) | Ertugliflozin 15 mg (n = 97) | |
Fasting plasma glucose, mg/dL | ||||||
LS mean (95% CI) | – 5.0 (– 15.0, 5.1) | – 11.8 (– 21.1, – 2.5) | – 20.5 (– 30.2, – 10.7) | – 13.5 (– 25.4, – 1.6) | – 6.5 (– 17.3, – 4.4) | – 14.4 (– 25.9, – 3.0) |
Difference in LS means (95% CI) versus placebo | – | – 6.8 (– 19.5, 5.9) | – 15.5 (– 28.5, – 2.5) | – | 7.1 (– 8.0, 22.2) | – 0.9 (– 16.4, 14.6) |
P valuea
| – | 0.291 | 0.019 | – | ND | ND |
Body weight, kg | ||||||
LS mean (95% CI) | 0.5 (– 0.1, 1.0) | – 1.3 (– 1.9, – 0.8) | – 1.4 (– 2.0, – 0.8) | 0.4 (– 0.5, 1.3) | – 1.3 (– 2.1, – 0.5) | – 1.3 (– 2.2, – 0.5) |
Difference in LS means (95% CI) versus placebo | – | – 1.8 (– 2.6, – 1.0) | – 1.8 (– 2.7, – 1.0) | – | – 1.7 (– 2.9, – 0.5) | – 1.7 (– 2.9, – 0.5) |
P valuea
| – | <0.001 | <0.001 | – | ND | ND |
Systolic blood pressure, mmHg | ||||||
LS mean (95% CI) | – 0.9 (– 3.7, 1.9) | – 2.3 (– 5.0, 0.3) | – 4.4 (– 7.1, – 1.6) | 1.0 (– 2.5, 4.5) | – 3.2 (– 6.4, – 0.1) | – 1.6 (– 5.0, 1.7) |
Difference in LS means (95% CI) versus placebo | – | – 1.4 (– 5.1, 2.3) | – 3.5 (– 7.2, 0.3) | – | – 4.2 (– 8.8, 0.3) | – 2.7 (– 7.4, 2.1) |
P valuea
| – | 0.451 | 0.072 | – | ND | ND |
Other Efficacy Endpoints
Safety
Number of patients, n (%) | Week 26 | Week 52 | ||||
---|---|---|---|---|---|---|
Placebo (n = 154) | Ertugliflozin 5 mg (n = 158) | Ertugliflozin 15 mg (n = 155) | Placebo (n = 154) | Ertugliflozin 5 mg (n = 158) | Ertugliflozin 15 mg (n = 155) | |
Overall safety | ||||||
Any AEs (IR) | 106 (68.8) | 113 (71.5) | 93 (60.0) | 125 (81.2) | 134 (84.8) | 115 (74.2) |
Drug-related AEsa (IR) | 15 (9.7) | 26 (16.5) | 11 (7.1) | 23 (14.9) | 39 (24.7) | 16 (10.3) |
Serious AEs (IR) | 17 (11.0) | 19 (12.0) | 15 (9.7) | 24 (15.6) | 26 (16.5) | 30 (19.4) |
AEs leading to discontinuation (IR) | 6 (3.9) | 11 (7.0) | 3 (1.9) | 8 (5.2) | 13 (8.2) | 6 (3.9) |
Deaths (IR) | 1 (0.6) | 2 (1.3) | 1 (0.6) | 3 (1.9)b
| 3 (1.9) | 4 (2.6) |
Pre-specified AEs | ||||||
Urinary tract infection (IR) | 11 (7.1) | 6 (3.8) | 7 (4.5) | 22 (14.3) | 9 (5.7)* | 19 (12.3) |
Genital mycotic infection (IR, women) | 0 (0) | 3 (4.1) | 1 (1.3) | 2 (2.4) | 4 (5.4) | 3 (3.8) |
Genital mycotic infection (IR, men) | 0 (0) | 3 (3.6) | 0 (0) | 0 (0) | 3 (3.6) | 0 (0) |
Hypovolemia (IR) | 0 (0) | 7 (4.4)†
| 3 (1.9) | 1 (0.6) | 7 (4.4)ǂ
| 4 (2.6) |
Symptomatic hypoglycemiac (ER) | 27 (17.5) | 33 (20.9) | 26 (16.8) | 35 (22.7) | 39 (24.7) | 28 (18.1) |