Introduction
Methods
Patients
Assessments and Data Analyses
Results
Patient Disposition, Exposure and Baseline Characteristics
Empagliflozin 25 mg/linagliptin 5 mg (n = 273) | Empagliflozin 10 mg/linagliptin 5 mg (n = 272) | Empagliflozin 25 mg (n = 276) | Empagliflozin 10 mg (n = 275) | Linagliptin 5 mg (n = 267) | |
---|---|---|---|---|---|
Male | 145 (53.1) | 158 (58.1) | 144 (52.2) | 146 (53.1) | 142 (53.2) |
Age, years | 55.7 (10.2) | 55.7 (10.0) | 55.6 (9.8) | 54.9 (10.5) | 55.0 (10.8) |
Race | |||||
White | 205 (75.1) | 204 (75.0) | 194 (70.3) | 209 (76.0) | 201 (75.3) |
Asian | 34 (12.5) | 32 (11.8) | 40 (14.5) | 32 (11.6) | 32 (12.0) |
Black/African American | 17 (6.2) | 24 (8.8) | 24 (8.7) | 17 (6.2) | 17 (6.4) |
Other | 17 (6.2) | 12 (4.4) | 18 (6.5) | 17 (6.2) | 17 (6.4) |
Time since diagnosis of type 2 diabetes, years | |||||
≤ 1 | 53 (19.4) | 65 (23.9) | 58 (21.0) | 57 (20.7) | 60 (22.5) |
> 1–5 | 101 (37.0) | 97 (35.7) | 100 (36.2) | 114 (41.5) | 106 (39.7) |
> 5–10 | 75 (27.5) | 73 (26.8) | 75 (27.2) | 55 (20.0) | 65 (24.3) |
> 10 | 44 (16.1) | 37 (13.6) | 43 (15.6) | 49 (17.8) | 36 (13.5) |
HbA1c, % | 7.94 (0.87) | 8.01 (0.89) | 8.01 (0.90) | 8.01 (0.98) | 8.03 (0.89) |
Weight, kg | 86.8 (19.4) | 86.9 (18.7) | 87.2 (18.6) | 86.8 (21.2) | 87.4 (19.7) |
Body mass index, kg/m2 | 31.3 (5.5) | 31.1 (5.6) | 31.5 (5.5) | 31.2 (5.5) | 31.2 (5.8) |
Systolic blood pressure, mmHg | 129.7 (15.2) | 128.9 (14.7) | 129.1 (14.0) | 130.1 (15.1) | 128.0 (13.9) |
Diastolic blood pressure, mmHg | 78.4 (9.1) | 78.7 (8.4) | 79.3 (8.9) | 79.7 (9.1) | 78.0 (8.8) |
Estimated glomerular filtration rate (MDRD), mL/min/1.73 m2 | 88.9 (18.8) | 88.5 (17.9) | 89.5 (18.4) | 89.8 (19.4) | 89.7 (20.1) |
Summary of Adverse Events
Empagliflozin 25 mg/linagliptin 5 mg (n = 273) | Empagliflozin 10 mg/linagliptin 5 mg (n = 272) | Empagliflozin 25 mg (n = 276) | Empagliflozin 10 mg (n = 275) | Linagliptin 5 mg (n = 267) | |
---|---|---|---|---|---|
One or more AE(s) | 201 (73.6) | 193 (71.0) | 196 (71.0) | 206 (74.9) | 188 (70.4) |
Most common AEsa | |||||
Urinary tract infection | 27 (9.9) | 29 (10.7) | 25 (9.1) | 30 (10.9) | 27 (10.1) |
Headache | 16 (5.9) | 15 (5.5) | 13 (4.7) | 19 (6.9) | 24 (9.0) |
Upper respiratory tract infection | 19 (7.0) | 19 (7.0) | 18 (6.5) | 13 (4.7) | 16 (6.0) |
Nasopharyngitis | 18 (6.6) | 16 (5.9) | 10 (3.6) | 16 (5.8) | 20 (7.5) |
Hyperglycemia | 8 (2.9) | 8 (2.9) | 12 (4.3) | 13 (4.7) | 24 (9.0) |
Arthralgia | 5 (1.8) | 14 (5.1) | 13 (4.7) | 10 (3.6) | 12 (4.5) |
One or more drug-relatedb AE(s) | 41 (15.0) | 37 (13.6) | 48 (17.4) | 42 (15.3) | 32 (12.0) |
One or more AE(s) leading to treatment discontinuation | 12 (4.4) | 10 (3.7) | 9 (3.3) | 16 (5.8) | 6 (2.2) |
One or more severe AE(s) | 19 (7.0) | 17 (6.3) | 14 (5.1) | 17 (6.2) | 9 (3.4) |
One or more serious AE(s) | 12 (4.4) | 16 (5.9) | 19 (6.9) | 16 (5.8) | 10 (3.7) |
Deaths | 0 | 2 (0.7) | 2 (0.7) | 2 (0.7) | 0 |
Hypoglycemia
Empagliflozin 25 mg/linagliptin 5 mg (n = 273) | Empagliflozin 10 mg/linagliptin 5 mg (n = 272) | Empagliflozin 25 mg (n = 276) | Empagliflozin 10 mg (n = 275) | Linagliptin 5 mg (n = 267) | |
---|---|---|---|---|---|
Confirmed hypoglycemic AEsa | 5 (1.8) | 3 (1.1) | 6 (2.2) | 6 (2.2) | 4 (1.5) |
Events requiring assistance | 0 | 0 | 0 | 0 | 0 |
Events consistent with urinary tract infectionb | 31 (11.4) | 34 (12.5) | 33 (12.0) | 38 (13.8) | 34 (12.7) |
Female | 25 (19.5) | 27 (23.7) | 28 (21.2) | 29 (22.5) | 29 (23.2) |
Male | 6 (4.1) | 7 (4.4) | 5 (3.5) | 9 (6.2) | 5 (3.5) |
Events consistent with genital infectionc | 11 (4.0) | 12 (4.4) | 18 (6.5) | 18 (6.5) | 7 (2.6) |
Female | 4 (3.1) | 9 (7.9) | 14 (10.6) | 11 (8.5) | 4 (3.2) |
Male | 7 (4.8) | 3 (1.9) | 4 (2.8) | 7 (4.8) | 3 (2.1) |
Events consistent with volume depletiond | 2 (0.7) | 5 (1.8) | 2 (0.7) | 1 (0.4) | 4 (1.5) |
Dehydration | 1 (0.4) | 1 (0.4) | 1 (0.4) | 0 | 2 (0.7) |
Hypotension | 1 (0.4) | 2 (0.7) | 0 | 1 (0.4) | 2 (0.7) |
Syncope | 0 | 2 (0.7) | 2 (0.7) | 0 | 0 |
Orthostatic hypotension | 0 | 0 | 0 | 0 | 1 (0.4) |
Hypersensitivity reactionse | 3 (1.1) | 2 (0.7) | 2 (0.7) | 2 (0.7) | 1 (0.4) |
Asthma | 0 | 1 (0.4) | 0 | 2 (0.7) | 0 |
Urticaria | 0 | 1 (0.4) | 2 (0.7) | 0 | 0 |
Angiodema | 1 (0.4) | 0 | 0 | 0 | 1 (0.4) |
Asthmatic crisis | 1 (0.4) | 0 | 0 | 0 | 0 |
Eyelid edema | 1 (0.4) | 0 | 0 | 0 | 0 |
Pancreatitisf | 1 (0.4) | 0 | 0 | 0 | 1 (0.4) |
Acute pancreatitis | 1 (0.4) | 0 | 0 | 0 | 0 |
Chronic pancreatitis | 0 | 0 | 0 | 0 | 1 (0.4) |
Decreased renal functiong | 1 (0.4) | 0 | 0 | 0 | 1 (0.4) |
Acute renal failure | 0 | 0 | 0 | 0 | 1 (0.4) |
Renal impairment | 1 (0.4) | 0 | 0 | 0 | 0 |
Cancer events | 5 (1.8) | 2 (0.7) | 2 (0.7) | 2 (0.7) | 2 (0.7) |
Adenoid cystic carcinoma | 0 | 0 | 0 | 1 (0.4) | 0 |
Basal cell carcinoma | 1 (0.4) | 0 | 1 (0.4) | 0 | 0 |
Breast cancer | 1 (0.4) | 0 | 0 | 0 | 0 |
Renal cancerh | 2 (0.7) | 0 | 0 | 0 | 0 |
Gastrointestinal carcinoma | 0 | 1 (0.4) | 0 | 0 | 0 |
Lung canceri | 0 | 1 (0.4) | 0 | 1 (0.4) | 0 |
Metastases to peritoneum | 0 | 0 | 1 (0.4) | 0 | 0 |
Ovarian cancer | 0 | 0 | 1 (0.4) | 0 | 0 |
Prostate cancerj | 1 (0.4) | 0 | 0 | 0 | 1 (0.4) |
Squamous cell carcinoma | 0 | 0 | 0 | 0 | 1 (0.4) |
Urinary Tract Infection
Genital Infection
Volume Depletion
Hypersensitivity Reactions, Pancreatitis and Diabetic Ketoacidosis
Renal Adverse Events and Laboratory Parameters
Cancer
Lipid Laboratory Parameters
Empagliflozin 25 mg/linagliptin 5 mg (n = 263)a | Empagliflozin 10 mg/linagliptin 5 mg (n = 267)b | Empagliflozin 25 mg (n = 268)c | Empagliflozin 10 mg (n = 261)d | Linagliptin 5 mg (n = 255)e | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change from baseline | Baseline | Change from baseline | Baseline | Change from baseline | Baseline | Change from baseline | Baseline | Change from baseline | |
Hematocrit, % | 42.2 (4.8) | 4.9 (3.8) | 42.4 (5.0) | 4.6 (3.8) | 42.5 (5.2) | 4.7 (3.9) | 42.9 (4.9) | 4.3 (3.6) | 42.3 (5.3) | 1.3 (3.8) |
Uric acid, mg/dL | 4.9 (1.9) | − 1.0 (1.4) | 5.3 (1.9) | − 1.1 (1.4) | 5.2 (2.0) | − 1.1 (1.6) | 5.1 (2.0) | − 0.9 (1.4) | 5.0 (2.0) | 0.1 (1.2) |
Creatinine, mg/dL | 0.9 (0.1) | 0.0 (0.1) | 0.9 (0.1) | 0.0 (0.1) | 0.9 (0.1) | − 0.0 (0.1) | 0.9 (0.1) | − 0.0 (0.1) | 0.9 (0.1) | 0.0 (0.1) |
Electrolytes | ||||||||||
Sodium, mEq/L | 141 (2) | 1 (2) | 141 (2) | 1 (2) | 141 (2) | 1 (2) | 141 (2) | 1 (2) | 141 (2) | 0 (2) |
Potassium, mEq/L | 4.1 (0.3) | 0.1 (0.3) | 4.1 (0.3) | 0.0 (0.3) | 4.1 (0.3) | 0.0 (0.3) | 4.2 (0.3) | 0.1 (0.4) | 4.1 (0.3) | 0.1 (0.3) |
Calcium, mg/dL | 9.7 (0.4) | − 0.0 (0.4) | 9.7 (0.4) | − 0.0 (0.4) | 9.7 (0.4) | − 0.0 (0.5) | 9.8 (0.4) | − 0.1 (0.5) | 9.7 (0.4) | − 0.1 (0.5) |
Magnesium, mEq/L | 1.8 (0.2) | 0.1 (0.1) | 1.8 (0.2) | 0.1 (0.2) | 1.8 (0.2) | 0.1 (0.1) | 1.8 (0.2) | 0.1 (0.1) | 1.8 (0.2) | 0.0 (0.2) |
Phosphate, mg/dL | 3.7 (0.2) | 0.1 (0.2) | 3.7 (0.2) | 0.0 (0.2) | 3.7 (0.2) | 0.1 (0.3) | 3.7 (0.2) | 0.1 (0.3) | 3.7 (0.2) | 0.0 (0.2) |
Total cholesterol, mg/dL | 176.6 (60.3) | 8.6 (46.7) | 178.0 (63.8) | 4.4 (54.5) | 182.1 (62.2) | 8.3 (52.8) | 186.4 (61.2) | 6.6 (45.2) | 184.8 (76.3) | − 2.9 (61.5) |
HDL-cholesterol, mg/dL | 43.1 (6.2) | 1.9 (3.4) | 42.0 (5.4) | 1.9 (3.5) | 43.0 (6.6) | 2.3 (3.9) | 42.6 (6.0) | 1.8 (3.6) | 42.5 (5.5) | 0.7 (3.3) |
LDL-cholesterol, mg/dL | 80.9 (27.8) | 1.9 (21.9) | 82.2 (30.5) | − 0.2 (26.5) | 81.6 (26.5) | 2.3 (22.8) | 83.8 (27.1) | 0.8 (21.7) | 83.8 (30.3) | − 1.6 (22.5) |
Triglycerides, mg/dL | 103.5 (63.4) | − 1.0 (45.5) | 108.3 (61.9) | 0.8 (51.6) | 116.2 (95.5) | − 7.5 (76.1) | 119.3 (80.1) | 0.5 (57.7) | 114.5 (147.9) | − 4.7 (110.0) |