50 毫克膜衣錠、100 毫克膜衣錠 januvia
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(sitagliptin phosphate) S-WPC-MK0431-T-052017a
dibasic calcium phosphate (calcium hydrogen phosphate, anhydrous) croscarmellose
sodiummagnesium stearatesodium stearyl fumaratepolyvinyl
alcohol polyethylene glycol (macrogol) talc titanium dioxide red iron oxide
yellow iron oxide
(incretin)DPP-4sitagliptin
GLP-1GIP
mL/min/1.73m 2 < 90 mL/min/1.73 m
2 )JANUVIA
2
2 JANUVIA
2 )
JANUVIA(
2
JANUVIA
250 mg/kg125 mg/kg (100 mg/day3222) sitagliptin1000 mg/kg/day (100 mg/day100)( )1000 mg/kg/day JANUVIA JANUVIA
Sitagliptinsitagliptin JANUVIA
JANUVIA18
SitagliptinCYP3A42C82C92D61A22C192B6CYP CYP3A4SitagliptinP(p-glycoprotein) Pdigoxinsitagliptin Sitagliptin - Sitagliptin ( )sitagliptinmetforminglyburidesimvastatin rosiglitazonewarfarin CYP3A4CYP2C8CYP2C9(OCT) sitagliptindigoxin Metforminsitagliptinmetformin (OCT )metforminsitagliptin OCT Sulfonylureassitagliptinglyburide (CYP2C9 )glyburide CYP2C9sulfonylurea(glipizidetolbutamideglimepiride) Simvastatinsitagliptinsimvastatin (CYP3A4 )sitagliptinCYP3A4 Thiazolidinedionessitagliptinrosiglitazone sitagliptinCYP2C8 pioglitazoneCYP2C8CYP3A4 pioglitazone Warfarinsitagliptinwarfarin(S(-) R(+) warfarin)(INR )S(-) warfarinCYP2C9 sitagliptinCYP2C9 sitagliptinnorethindroneethinyl estradiol DigoxinSitagliptindigoxin10 0.25digoxin100JANUVIAdigoxinAUC11%Cmax
18%digoxin sitagliptin sitagliptin Metforminmetforminsitagliptin sitagliptin Cyclosporinecyclosporine (P)sitagliptin 100JANUVIA600 cyclosporinesitagliptinAUCCmax29%68% sitagliptinsitagliptin P sitagliptin (statinsfibratesezetimibe) (clopidogrel)(ACE
hydrochlorothiazide) ( naproxendiclofenaccelecoxib)(bupropionfluoxetinesertraline) (cetirizine)(omeprazolelansoprazole) (sildenafil)
2 50)7,339
JANUVIA 100 (WBC 200 cells/microLWBC6600 cells/microL) ()
800JANUVIA 800JANUVIAQTc () 800I 600JANUVIA400JANUVIA28 () sitagliptin34 13.5% sitagliptin
Glucagons
sitagliptinAUC14%SitagliptinAUC
t1/212.4350 mL/min
SitagliptinSitagliptin
hOAT-3sitagliptinhOAT-3sitagliptin
(ESRD)
JANUVIA
rate (eGFR) ≥ 60 mL/min/1.73 m 2 < 90 mL/min/1.73 m
2 )eGFR ≥ 45
2 sitagliptinAUC1.2
2sitagliptinAUC
4sitagliptin (434
sitagliptin()
III
(National Cholesterol Education Program; NCEP)
55
(FPG)2(PPG)(glipizide)
52
JANUVIA()
(HOMA-IR)
)FPG(18-19.3 mg/dL
24-15.8 mg/dL)
() 8.04 8.05 8.01 8.03
(‡) -0.48 0.12 -0.61 0.18
(‡) -0.60§ -0.79§
HbA1c<7%(%) 69 (35.8) 16 (15.5) 93 (40.6) 41 (16.8)
HbA1c
HbA1c (%)9% N=27 N=20 M=37 N=35
() 9.48 9.48 9.59 9.46
(‡) -0.83 0.37 -1.27 0.25
(‡) -1.20 -1.52
HbA1c (%)8%<9% N=70 N=25 N=62 N=82
() 8.40 8.38 8.36 8.41
(‡) -0.42 0.19 -0.64 0.16
(‡) -0.61 -0.80
HbA1c (%)<8% N=96 N=58 N=130 N=127
() 7.37 7.41 7.39 7.39
(‡) -0.42 0.02 -0.40 0.17
(‡) -0.44 -0.57 † () ‡ § p<0.001
2 † 1824JANUVIA
FPG (mg/dL) N=201 N=107 N=234 N=247
() 179.8 183.6 170.2 176.1
(‡) -12.7 7.0 -12.4 4.7
(‡) -19.7§ -17.1§
() 257.2 270.8
(‡) -48.9 -2.2
() 89.5 91.3 83.9 83.3
(‡) -0.6 -0.7 -0.2 -1.1
(‡) 0.1# 0.9†† † ()
JANUVIAHbA1c1.05% (JANUVIA
mg/dL (JANUVIA -22.5 mg/dL9.4 mg/dL
p<0.001)
HbA1c-1.06%
metformin-1.59%50sitagliptin500metformin-
Metformin 1000 mg
bid
HbA1c (%) N=165 N=175 N=178 N=183 N=177 N=178
() 8.68 8.87 8.90 8.79 8.68 8.76
( ‡ ) 0.17 -0.66 -0.82 -1.40 -1.13 -1.90
( ‡ ) - -0.83
(23.0)
79 (43.2) 68 (38.4) 118 (66.3)
FPG (mg/dL) N=169 N=178 N=179 N=183 N=179 N=180
() 196.3 201.4 205.2 203.9 197.0 196.7
( ‡ ) 5.8 -17.5 -27.3 -47.1 -29.3 -63.9
( ‡ ) - -23.9
§
2 PPG (mg/dL) N=129 N=136 N=141 N=147 N=138 N=152
() 276.8 285.4 292.7 291.8 283.4 286.9
( ‡ ) 0.3 -51.9 -53.4 -92.5 -78.0 -116.6
( ‡ ) - -52.2
§
() N=169 N=175 N=179 N=184 N=175 N=178
() 90.1 85.9 88.1 90.0 89.4 88.2
( ‡ ) -0.9 0.0 -0.9 -0.6 -1.1 -1.3
( ‡ ) 0.9
¶ p=0.005
# (P0.05)
(N=117)sitagliptin 50
11.15%314.4 mg/dL441.0 mg/dL24HbA1cFPG2PPG
-2.94%-126.7 mg/dL-207.9 mg/dL
24(1.3)
1,500100JANUVIA
(HOMA-IR)(HOMA-)
() 7.96 8.03
(‡) -0.67 -0.02
+metformin(‡) -0.65§
FPG (mg/dL) N=454 N=226
() 170.0 173.5
(‡) -16.9 8.5
+metformin(‡) -25.4§
() 274.5 272.4
(‡) -62.0 -11.4
+metformin(‡) -50.6§
() 86.9 87.6
(‡) -0.7 -0.6
¶ +metformin(P0.05)
7.9%FPG156 mg/dLPPG244 mg/dL12
50JANUVIAmetforminHbA1c (-0.39%
P<0.001)2PPG (-29.0 mg/dL17.8 mg/dLP<0.001)
Metformin
(4)
metformin5005
JANUVIA 11.6% metformin
20.7%(JANUVIA, 3.6%; metformin,
10.9%) (1.1%, 3.1%)(2.1%, 3.8%)(0.4%, 1.3%)
(JANUVIA, 1.7%; metformin, 3.4%)
(JANUVIA, -0.6 kg; metformin -1.9 kg)
Glipizide
5 mg/dayFPG18<110
mg/dL20
glipizide0.67%JANUVIA
HbA1c(≥9%)HbA1c
(JANUVIA-1.68%glipizide-1.76%)
100 JANUVIA 30 pioglitazone
30 pioglitazone
≥10% HbA1c JANUVIA pioglitazone (N=99)-3.00%
pioglitazone (N=88)-2.06% HbA1c <10%(
N=152 N=158)-1.99%-1.14%BMI
HbA1cJANUVIA pioglitazone
(24) †
‡ ) -2.38 -1.49
pioglitazone( ‡ ) -0.89
§
HbA1c<7%(%) 151 (60%) 68 (28%) FPG (mg/dL) N = 256 N = 253 () 203.3 200.7 (
‡ ) -63.0 -40.2
pioglitazone( ‡ ) -22.8
2PPG (mg/dL) N = 216 N = 211 () 282.7 284.1 (
‡ ) -113.6 -68.9
pioglitazone( ‡ ) -44.7
() 80.4 80.7 (
(APaT)
30-45100
JANUVIAHbA1c
pioglitazoneJANUVIApioglitazoneHbA1cFPG
(HOMA-IR)(HOMA-)
JANUVIA
JANUVIA
() 8.05 8.00
( ‡ ) -0.85 -0.15
+pioglitazone( ‡ ) -0.70
FPG (mg/dL) N=163 N=174
() 168.3 165.6
( ‡ ) -16.7 1.0
+pioglitazone( ‡ ) -17.7
() 90.0 85.6
( ‡ ) 1.8 1.5
+pioglitazone( ‡ ) 0.2
Glimepiride Glimepiride Metformin
100JANUVIA
(HOMA-IR)(HOMA-β)
JANUVIA
() 8.41 8.46 8.27 8.28
( ‡ ) -0.30 0.27 -0.59 0.30
( ‡ ) -0.57
§
HbA1c<7%(%) 11 (10.8) 9 (8.7) 26 (22.6) 1 (1.0)
FPG (mg/dL) N=104 N=104 N=115 N=109
() 183.5 184.6 179.3 178.9
( ‡ ) -0.9 18.4 -7.8 12.9
( ‡ ) -19.3
() 85.7 81.5 86.5 84.6
( ‡ ) 1.1 0.0 0.4 -0.7
( ‡ ) -1.1
RosiglitazoneMetformin
262JANUVIAmetforminrosiglitazone
rosiglitazone (≥4)
rosiglitazone 18 HbA1cFPG 2 PPG( 8)
JANUVIA
18 54() †
+ Metformin +
Rosiglitazone
HbA1c (%) N = 168 N = 88 N = 168 N = 88 () 8.81 8.73 8.81 8.73 (‡) -1.03 -0.31 -1.05 -0.28 +rosiglitazone+metformin (‡)
-0.72§ -0.77§
HbA1c<7%(%) 37 (22%) 8 (9%) 44 (26%) 12 (14%)
FPG (mg/dL) N = 169 N = 89 N = 169 N = 89 () 182.1 183.5 182.1 183.5 (‡) -30.7 -11.7 -28.0 -10.7 + rosiglitazone + metformin (‡)
-19.0§ -17.4§
2- PPG (mg/dL) N = 142 N = 75 N = 147 N = 77
() 257.8 249.5 256.6 247.7 (‡) -59.9 -22.0 -50.7 -16.6 + rosiglitazone + metformin (‡)
-37.9§ -34.1§
()
N = 157 N = 79 N = 115 N = 40 () 82.1 87.0 82.0 85.6 (‡) 0.5 0.2 1.9 1.3 + rosiglitazone + metformin (‡)
0.3¶ 0.6¶
(Metformin)
641JANUVIA(metformin)
metformin (≥1500)
100JANUVIAHbA1c
JANUVIA
(24) †
() 8.72 8.64
(‡) -0.59 -0.03
+metformin(‡) -0.56
FPG (mg/dL) N = 310 N = 313
() 175.8 179.1
(‡) -18.5 -3.5
() 290.9 292.1
(‡) -30.9 5.2
() 86.6 87.4
(‡) 0.1 0.1
24JANUVIA(insulin-
)100
insulin glargine
metformin)-55.5 mg/dL(metformin)
JANUVIA(metformin)25.2%(
50)(7,332)(7,339)eGFR <30 mL/min/1.73 m 2
2,00475()3,324(eGFR
(0.70; 95% CI, 0.630.79; p<0.001)
(0.88–1.09)
0.99
0.99
1.03
0.95
0.97
0.90
1.01
1.00
† Cox p 1.3 p
‡
Shotton Lane, Cramlington, Northumberland, NE23 3JU, United Kingdom.
dibasic calcium phosphate (calcium hydrogen phosphate, anhydrous) croscarmellose
sodiummagnesium stearatesodium stearyl fumaratepolyvinyl
alcohol polyethylene glycol (macrogol) talc titanium dioxide red iron oxide
yellow iron oxide
(incretin)DPP-4sitagliptin
GLP-1GIP
mL/min/1.73m 2 < 90 mL/min/1.73 m
2 )JANUVIA
2
2 JANUVIA
2 )
JANUVIA(
2
JANUVIA
250 mg/kg125 mg/kg (100 mg/day3222) sitagliptin1000 mg/kg/day (100 mg/day100)( )1000 mg/kg/day JANUVIA JANUVIA
Sitagliptinsitagliptin JANUVIA
JANUVIA18
SitagliptinCYP3A42C82C92D61A22C192B6CYP CYP3A4SitagliptinP(p-glycoprotein) Pdigoxinsitagliptin Sitagliptin - Sitagliptin ( )sitagliptinmetforminglyburidesimvastatin rosiglitazonewarfarin CYP3A4CYP2C8CYP2C9(OCT) sitagliptindigoxin Metforminsitagliptinmetformin (OCT )metforminsitagliptin OCT Sulfonylureassitagliptinglyburide (CYP2C9 )glyburide CYP2C9sulfonylurea(glipizidetolbutamideglimepiride) Simvastatinsitagliptinsimvastatin (CYP3A4 )sitagliptinCYP3A4 Thiazolidinedionessitagliptinrosiglitazone sitagliptinCYP2C8 pioglitazoneCYP2C8CYP3A4 pioglitazone Warfarinsitagliptinwarfarin(S(-) R(+) warfarin)(INR )S(-) warfarinCYP2C9 sitagliptinCYP2C9 sitagliptinnorethindroneethinyl estradiol DigoxinSitagliptindigoxin10 0.25digoxin100JANUVIAdigoxinAUC11%Cmax
18%digoxin sitagliptin sitagliptin Metforminmetforminsitagliptin sitagliptin Cyclosporinecyclosporine (P)sitagliptin 100JANUVIA600 cyclosporinesitagliptinAUCCmax29%68% sitagliptinsitagliptin P sitagliptin (statinsfibratesezetimibe) (clopidogrel)(ACE
hydrochlorothiazide) ( naproxendiclofenaccelecoxib)(bupropionfluoxetinesertraline) (cetirizine)(omeprazolelansoprazole) (sildenafil)
2 50)7,339
JANUVIA 100 (WBC 200 cells/microLWBC6600 cells/microL) ()
800JANUVIA 800JANUVIAQTc () 800I 600JANUVIA400JANUVIA28 () sitagliptin34 13.5% sitagliptin
Glucagons
sitagliptinAUC14%SitagliptinAUC
t1/212.4350 mL/min
SitagliptinSitagliptin
hOAT-3sitagliptinhOAT-3sitagliptin
(ESRD)
JANUVIA
rate (eGFR) ≥ 60 mL/min/1.73 m 2 < 90 mL/min/1.73 m
2 )eGFR ≥ 45
2 sitagliptinAUC1.2
2sitagliptinAUC
4sitagliptin (434
sitagliptin()
III
(National Cholesterol Education Program; NCEP)
55
(FPG)2(PPG)(glipizide)
52
JANUVIA()
(HOMA-IR)
)FPG(18-19.3 mg/dL
24-15.8 mg/dL)
() 8.04 8.05 8.01 8.03
(‡) -0.48 0.12 -0.61 0.18
(‡) -0.60§ -0.79§
HbA1c<7%(%) 69 (35.8) 16 (15.5) 93 (40.6) 41 (16.8)
HbA1c
HbA1c (%)9% N=27 N=20 M=37 N=35
() 9.48 9.48 9.59 9.46
(‡) -0.83 0.37 -1.27 0.25
(‡) -1.20 -1.52
HbA1c (%)8%<9% N=70 N=25 N=62 N=82
() 8.40 8.38 8.36 8.41
(‡) -0.42 0.19 -0.64 0.16
(‡) -0.61 -0.80
HbA1c (%)<8% N=96 N=58 N=130 N=127
() 7.37 7.41 7.39 7.39
(‡) -0.42 0.02 -0.40 0.17
(‡) -0.44 -0.57 † () ‡ § p<0.001
2 † 1824JANUVIA
FPG (mg/dL) N=201 N=107 N=234 N=247
() 179.8 183.6 170.2 176.1
(‡) -12.7 7.0 -12.4 4.7
(‡) -19.7§ -17.1§
() 257.2 270.8
(‡) -48.9 -2.2
() 89.5 91.3 83.9 83.3
(‡) -0.6 -0.7 -0.2 -1.1
(‡) 0.1# 0.9†† † ()
JANUVIAHbA1c1.05% (JANUVIA
mg/dL (JANUVIA -22.5 mg/dL9.4 mg/dL
p<0.001)
HbA1c-1.06%
metformin-1.59%50sitagliptin500metformin-
Metformin 1000 mg
bid
HbA1c (%) N=165 N=175 N=178 N=183 N=177 N=178
() 8.68 8.87 8.90 8.79 8.68 8.76
( ‡ ) 0.17 -0.66 -0.82 -1.40 -1.13 -1.90
( ‡ ) - -0.83
(23.0)
79 (43.2) 68 (38.4) 118 (66.3)
FPG (mg/dL) N=169 N=178 N=179 N=183 N=179 N=180
() 196.3 201.4 205.2 203.9 197.0 196.7
( ‡ ) 5.8 -17.5 -27.3 -47.1 -29.3 -63.9
( ‡ ) - -23.9
§
2 PPG (mg/dL) N=129 N=136 N=141 N=147 N=138 N=152
() 276.8 285.4 292.7 291.8 283.4 286.9
( ‡ ) 0.3 -51.9 -53.4 -92.5 -78.0 -116.6
( ‡ ) - -52.2
§
() N=169 N=175 N=179 N=184 N=175 N=178
() 90.1 85.9 88.1 90.0 89.4 88.2
( ‡ ) -0.9 0.0 -0.9 -0.6 -1.1 -1.3
( ‡ ) 0.9
¶ p=0.005
# (P0.05)
(N=117)sitagliptin 50
11.15%314.4 mg/dL441.0 mg/dL24HbA1cFPG2PPG
-2.94%-126.7 mg/dL-207.9 mg/dL
24(1.3)
1,500100JANUVIA
(HOMA-IR)(HOMA-)
() 7.96 8.03
(‡) -0.67 -0.02
+metformin(‡) -0.65§
FPG (mg/dL) N=454 N=226
() 170.0 173.5
(‡) -16.9 8.5
+metformin(‡) -25.4§
() 274.5 272.4
(‡) -62.0 -11.4
+metformin(‡) -50.6§
() 86.9 87.6
(‡) -0.7 -0.6
¶ +metformin(P0.05)
7.9%FPG156 mg/dLPPG244 mg/dL12
50JANUVIAmetforminHbA1c (-0.39%
P<0.001)2PPG (-29.0 mg/dL17.8 mg/dLP<0.001)
Metformin
(4)
metformin5005
JANUVIA 11.6% metformin
20.7%(JANUVIA, 3.6%; metformin,
10.9%) (1.1%, 3.1%)(2.1%, 3.8%)(0.4%, 1.3%)
(JANUVIA, 1.7%; metformin, 3.4%)
(JANUVIA, -0.6 kg; metformin -1.9 kg)
Glipizide
5 mg/dayFPG18<110
mg/dL20
glipizide0.67%JANUVIA
HbA1c(≥9%)HbA1c
(JANUVIA-1.68%glipizide-1.76%)
100 JANUVIA 30 pioglitazone
30 pioglitazone
≥10% HbA1c JANUVIA pioglitazone (N=99)-3.00%
pioglitazone (N=88)-2.06% HbA1c <10%(
N=152 N=158)-1.99%-1.14%BMI
HbA1cJANUVIA pioglitazone
(24) †
‡ ) -2.38 -1.49
pioglitazone( ‡ ) -0.89
§
HbA1c<7%(%) 151 (60%) 68 (28%) FPG (mg/dL) N = 256 N = 253 () 203.3 200.7 (
‡ ) -63.0 -40.2
pioglitazone( ‡ ) -22.8
2PPG (mg/dL) N = 216 N = 211 () 282.7 284.1 (
‡ ) -113.6 -68.9
pioglitazone( ‡ ) -44.7
() 80.4 80.7 (
(APaT)
30-45100
JANUVIAHbA1c
pioglitazoneJANUVIApioglitazoneHbA1cFPG
(HOMA-IR)(HOMA-)
JANUVIA
JANUVIA
() 8.05 8.00
( ‡ ) -0.85 -0.15
+pioglitazone( ‡ ) -0.70
FPG (mg/dL) N=163 N=174
() 168.3 165.6
( ‡ ) -16.7 1.0
+pioglitazone( ‡ ) -17.7
() 90.0 85.6
( ‡ ) 1.8 1.5
+pioglitazone( ‡ ) 0.2
Glimepiride Glimepiride Metformin
100JANUVIA
(HOMA-IR)(HOMA-β)
JANUVIA
() 8.41 8.46 8.27 8.28
( ‡ ) -0.30 0.27 -0.59 0.30
( ‡ ) -0.57
§
HbA1c<7%(%) 11 (10.8) 9 (8.7) 26 (22.6) 1 (1.0)
FPG (mg/dL) N=104 N=104 N=115 N=109
() 183.5 184.6 179.3 178.9
( ‡ ) -0.9 18.4 -7.8 12.9
( ‡ ) -19.3
() 85.7 81.5 86.5 84.6
( ‡ ) 1.1 0.0 0.4 -0.7
( ‡ ) -1.1
RosiglitazoneMetformin
262JANUVIAmetforminrosiglitazone
rosiglitazone (≥4)
rosiglitazone 18 HbA1cFPG 2 PPG( 8)
JANUVIA
18 54() †
+ Metformin +
Rosiglitazone
HbA1c (%) N = 168 N = 88 N = 168 N = 88 () 8.81 8.73 8.81 8.73 (‡) -1.03 -0.31 -1.05 -0.28 +rosiglitazone+metformin (‡)
-0.72§ -0.77§
HbA1c<7%(%) 37 (22%) 8 (9%) 44 (26%) 12 (14%)
FPG (mg/dL) N = 169 N = 89 N = 169 N = 89 () 182.1 183.5 182.1 183.5 (‡) -30.7 -11.7 -28.0 -10.7 + rosiglitazone + metformin (‡)
-19.0§ -17.4§
2- PPG (mg/dL) N = 142 N = 75 N = 147 N = 77
() 257.8 249.5 256.6 247.7 (‡) -59.9 -22.0 -50.7 -16.6 + rosiglitazone + metformin (‡)
-37.9§ -34.1§
()
N = 157 N = 79 N = 115 N = 40 () 82.1 87.0 82.0 85.6 (‡) 0.5 0.2 1.9 1.3 + rosiglitazone + metformin (‡)
0.3¶ 0.6¶
(Metformin)
641JANUVIA(metformin)
metformin (≥1500)
100JANUVIAHbA1c
JANUVIA
(24) †
() 8.72 8.64
(‡) -0.59 -0.03
+metformin(‡) -0.56
FPG (mg/dL) N = 310 N = 313
() 175.8 179.1
(‡) -18.5 -3.5
() 290.9 292.1
(‡) -30.9 5.2
() 86.6 87.4
(‡) 0.1 0.1
24JANUVIA(insulin-
)100
insulin glargine
metformin)-55.5 mg/dL(metformin)
JANUVIA(metformin)25.2%(
50)(7,332)(7,339)eGFR <30 mL/min/1.73 m 2
2,00475()3,324(eGFR
(0.70; 95% CI, 0.630.79; p<0.001)
(0.88–1.09)
0.99
0.99
1.03
0.95
0.97
0.90
1.01
1.00
† Cox p 1.3 p
‡
Shotton Lane, Cramlington, Northumberland, NE23 3JU, United Kingdom.
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