Table A2: Baseline Characteristics of Patients Receiving Vildagliptin Monotherapy (Safety

Online Appendix

Table A1: Study design and inclusion/exclusion criteria for studies used in pooled analysis of efficacy and safety of vildagliptin monotherapy

Duration / Treatment arms / Age (y) / A1C (%) / FPG (mmol/L) / BMI
(kg/m2) / Exclusion
Study 1 (1) / 24 wk / Vilda 50 mg qd / 18-80 / 7.5-10.0 / <15 / 22-45 / ALT, AST >3x ULN
Vilda 50 mg bid / Direct bilirubin >1.3x ULN
Vilda 100 mg qd / Serum creatinine >220 µmol/L
placebo / TSH outside normal range
TG > 7.9 mmol/L
Study 2 (2) / 24 wk / Vilda 50 mg qd / 18-80 / 7.5-10.0 / <15 / 22-45 / ALT, AST >3x ULN
Vilda 50 mg bid / Direct bilirubin >1.3x ULN
Vilda 100 mg qd / Serum creatinine >220 µmol/L
placebo / TSH outside normal range
TG > 7.9 mmol/L
Study 3 (3) / 24 wk / Vilda 100 mg qd / 18-80 / 7.5-10.0 / <15 / 22-45 / ALT, AST >2.5x ULN
Pio 30 mg qd / Direct bilirubin >1.3x ULN
Vilda 50 mg + Pio 15 mg qd / Serum creatinine >220 µmol/L
Vilda 100 mg + Pio 30 mg qd / Clin. sign. TSH outside normal range
TG > 7.9 mmol/L
Study 4 (4) / 24 wk / Vilda 50 mg bid / 18-80 / 7.5-11.0 / <15 / 22-45 / ALT, AST >2.5x ULN
Rosi 8 mg qd / Direct bilirubin >1.3x ULN
Serum creatinine >220 µmol/L
TSH outside normal range
TG >7.9 mmol/L
Study 5 (5) / 52 wk / Vilda 50 mg bid / 18-78 / 7.5-11.0 / <15 / 22-45 / ALT, AST >3x ULN
Met up to 1000 mg bid / Direct bilirubin >1.3x ULN
Serum creatinine >132 µmol/L
Clin. sign. TSH outside normal range
TG >7.9 mmol/L
Study 6 / 12 wk / Vilda 50 mg qd / ≥18 / 9.0-11.0 / — / 22-45 / ALT, AST >2.5x ULN
NCT / Vilda 50 mg bid / Direct bilirubin >1.3x ULN
00101673 / Pio 30 mg qd / Serum creatinine >220 µmol/L
TSH outside normal range
C-peptide <2.0 nmol/L
TG > 7.9 mmol/L
Study 7 (6) / 12 wk / Vilda 100 mg qd / 30-75 / 6.8-10.0 / <15 / 22-42 / ALT, AST, alk. phos. >2x ULN
Vilda 50 mg qd / Direct bilirubin >1.3x ULN
Vilda 25 mg qd / Serum creatinine >220 µmol/L
Vilda 25 mg bid / TSH outside normal range
Placebo / C-peptide <2.0 nmol/L
TG >4.5 mmol/L
Study 8 (7) / 12 wk / Vilda 25 mg bid / ≥30 / 6.8-11.0 / <15 / 20-42 / ALT, AST, alk. phos. >2x ULN
Placebo / Direct bilirubin >1.3x ULN
Serum creatinine >220 µmol/L
TSH outside normal range
C-peptide <2.0 nmol/L
TG > 4.5 mmol/L

Table A2: Baseline characteristics of patients receiving vildagliptin monotherapy (Safety Population)

Mean ± SD or n (%) / All patients / Patients Aged <65 years / Patients Aged ≥65 years
N / 2264 / 1890 / 374
Age (y) / 53.3 ± 11.4 / 49.9 ± 9.1 / 70.3 ± 4.2
Sex: n (%) male / 1216 (53.7) / 1045 (55.3) / 171 (45.7)
Race
Caucasian / 1530 (67.6) / 1201 (63.5) / 329 (87.9)
Hispanic or Latino / 293 (12.9) / 274 (14.5) / 19 (5.1)
Black / 176 (7.8) / 166 (8.8) / 10 (2.7)
All other / 256 (11.7) / 249 (13.2) / 16 (4.3)
Weight (kg) / 90.2 ± 19.9 / 91.7 ± 20.4 / 83.3 ± 15.7
BMI (kg/m2) / 31.9 ± 5.7 / 32.2 ± 5.8 / 30.4 ± 4.6
BMI subgroup
<30 kg/m2 / 966 (42.7) / 770 (40.7) / 196 (52.4)
≥30 kg/m2 / 1297 (57.3) / 1119 (59.2) / 178 (47.6)
<35 kg/m2 / 1631 (72.0) / 1319 (69.8) / 312 (83.4)
≥35 kg/m2 / 632 (27.9) / 570 (30.2) / 62 (16.6)
not recorded / 1 / 1 / 0
A1C (%) / 8.6 ± 1.1 / 8.7 ± 1.1 / 8.3 ± 1.1
A1C subgroup
≤8.0% / 840 (37.1) / 658 (34.8) / 182 (48.7)
>8.0% / 1319 (58.3) / 1148 (60.7) / 171 (45.7)
≤9.0% / 1447 (63.9) / 1175 (62.2) / 272 (72.7)
>9.0% / 712 (31.4) / 631 (33.4) / 81 (21.7)
not recorded / 105 (4.6) / 84 (4.4) / 21 (5.6)
FPG (mmol/L) / 10.1 ± 2.7 / 10.3 ± 2.8 / 9.5 ± 2.2
Disease duration (y) / 2.2 ± 3.5 / 2.0 ± 3.2 / 3.2 ± 4.9
Serum creatinine (µmol/L) / 77.8 ± 17.0 / 76.6 ± 16.4 / 84.0 ± 18.7
Blood Pressure (mm Hg)
Diastolic / 81.2 ± 8.3 / 81.5 ± 8.3 / 79.9 ± 8.2
Systolic / 131.9 ± 14.3 / 130.7 ± 14.1 / 138.1 ± 13.9
GFR (MDRD)*
Normal renal function / 1468 (64.9) / 1356 (71.8) / 112 (30.0)
Mild impairment / 765 (33.8) / 523 (27.7) / 242 (64.7)
Medical History – cardiovascular risk factors (CVRF)
Any CVRF / 1498 (66.2) / 1177 (62.3) / 321 (85.8)
Diagnosed hypertension / 1135 (50.1) / 853 (45.1) / 282 (75.4)
Diagnosed dyslipidemia / 878 (38.8) / 687 (36.4) / 191 (51.1)
Coronary Artery Disease / 261 (11.5) / 168 (8.9) / 93 (24.9)
Patients with ≥5 concomitant medications / 405 (17.9) / 281 (14.9) / 124 (33.2)
*Glomerular Filtration Rate (GFR) determined with MDRD method: normal renal function GFR >80 mL/min x 1.73/m2; mild impairment, GFR ≤80 and >50 mL/min x 1.73/m2

Table A3: Most Common Specific AEs (occurring in >5% of any group of elderly patients)

Overall / Age <65 years / Age ≥65 years
Vildagliptin / Active
Comparator / Placebo / Vildagliptin / Active
Comparator / Placebo / Vildagliptin / Active
Comparator / Placebo
N / 2264 / 735 / 347 / 1890 / 619 / 293 / 374 / 116 / 54
Nasopharyngitis / 160 (7.1) / 51 (6.9) / 21 (6.1) / 134 (7.1) / 42 (6.8) / 19 (6.5) / 26 (7.0) / 9 (7.8) / 2 (3.7)
Upper Resp. Infection / 104 (4.6) / 31 (4.2) / 16 (4.6) / 80 (4.2) / 27 (4.4) / 14 (4.8) / 24 (6.4) / 4 (3.4) / 2 (3.7)
Dizziness / 123 (5.4) / 36 (4.9) / 14 (4.0) / 103 (5.4) / 33 (5.3) / 13 (4.4) / 20 (5.3) / 3 (2.6) / 1 (1.9)
Peripheral edema / 47 (2.1) / 37 (5.0) / 4 (1.2) / 36 (1.9) / 30 (4.8) / 4 (1.4) / 11 (2.9) / 7 (6.0) / 0
Sinusitis / 47 (2.1) / 10 (1.4) / 10 (2.9) / 38 (2.0) / 8 (1.3) / 7 (2.4) / 9 (2.4) / 2 (1.7) / 3 (5.6)
Diarrhea / 57 (2.5) / 78 (10.6) / 10 (2.9) / 50 (2.6) / 65 (10.5) / 8 (2.7) / 7 (1.9) / 13 (11.2) / 2 (3.7)
Nausea / 58 (2.6) / 31 (4.2) / 10 (2.9) / 51 (2.7) / 24 (3.9) / 9 (3.1) / 7 (1.9) / 7 (6.0) / 1 (1.9)

Reference List

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