![[CD3.25] chon thuoc dtd [CD3.25] chon thuoc dtd](https://image.slidesharecdn.com/cd3-240923084619-30364121/85/CD3-25-chon-thuoc-dtd-CD3-25-chon-thuoc-dtd-13-320.jpg)
![[CD3.25] chon thuoc dtd [CD3.25] chon thuoc dtd](https://image.slidesharecdn.com/cd3-240923084619-30364121/85/CD3-25-chon-thuoc-dtd-CD3-25-chon-thuoc-dtd-14-320.jpg)
![Nh動ng t叩c 畛ng ti畛m 畉n l棚n bi畉n c畛 tim m畉ch
c畛a c叩c nh坦m thu畛c i畛u tr畛 T
Nh畛ng NC quan s叩t v ph但n t鱈ch g畛p: SU c坦 th畛 li棚n quan
畉n vi畛c tng nguy c董 bi畉n c畛 tim m畉ch, nh動ng ch動a c坦 c叩c
NC th畛 nghi畛m l但m sng 畛 叩nh gi叩 t叩c 畛ng ti畛m 畉n ny1
C坦 nhi畛u b畉ng ch畛ng tr叩i ng動畛c v畛 畉nh h動畛ng tim m畉ch
c畛a c叩c thu畛c nh坦m thiazolidinedione2,3
TZD b畛 ch畛ng ch畛 畛nh tr棚n suy tim 畛 III v IV4,5
C叩c ph但n t鱈ch g畛p g畉n 但y: i畛u tr畛 gi畉m H t鱈ch c畛c 畉nh
h動畛ng kh担ng c坦 箪 ngh挑a th畛ng k棚 l棚n t畛 vong TM hay t畛 vong
do m畛i nguy棚n nh但n, nh動ng c坦 th畛 li棚n quan 畉n gi畉m nguy
c董 NMCT kh担ng t畛 vong6,7
1. Rao AD, et al. Diabetes Care. 2008;31:1672-1678; 2. Home PD, et al. Lancet. 2009;373:2125-2135; 3. Dormandy JA, et al. Lancet. 2005;366:1279-
1289; 4. Avandia [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; May 2011; 5. Actos [prescribing information]. Deerfield, IL:
Takeda Pharmaceutical America, Inc.; July 2011; 6. Boussageon R, et al. BMJ. 2011;343:d4169; 7. Hemmingsen B, et al. BMJ. 2011;343:d6898.](https://image.slidesharecdn.com/cd3-240923084619-30364121/85/CD3-25-chon-thuoc-dtd-CD3-25-chon-thuoc-dtd-20-320.jpg)
![T畛 l畛 h畉 動畛ng huy畉t c畛a c叩c SU
*H畉 H: 動畛ng huy畉t mao m畉ch ng坦n tay 50 mg/dL (2.75 mmol/L)
1Glucovance [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2004. 2UKPDS Group. Lancet. 1998; 352: 837853.
3Draeger KE, et al. Horm Metab Res. 1996; 28: 419425. 4McGavin JK, et al. Drugs. 2002; 62; 13571364.
5Metaglip [package insert]. Princeton, NJ: Bristol-Myers Squibb Company, 2002.
Sulfonylureas
Glipizide5
Gliclazide4
Chlorpropamide2
Glyburide1
0
5
10
15
20
25
T畛
l畛
b畛
h畉
Hm畛i
(%)
21.3%
15.3%
5%
2.9%*
14%
11%
Glibenclamide3 Glimepiride3](https://image.slidesharecdn.com/cd3-240923084619-30364121/85/CD3-25-chon-thuoc-dtd-CD3-25-chon-thuoc-dtd-24-320.jpg)
![46
Vildagliptin kh担ng lm tng nguy c董 & t畛 l畛 m畛i m畉c c叩c
bi畉n c畛 tim m畉ch ch鱈nh (MACE) 畛 ng動畛i cao tu畛i > 65 tu畛i
Vildagliptin
n/N (%)
Comparators
n/N (%)
M-H RR
(95% CI)
0.74 (0.52-1.05)
64/3928 (1.63)
57/5310 (1.07)
Male
0. 1 1.0 10.0 100.0
0.01
Vildagliptin better Comparator better
i) MACE in subgroups by age, gender, and CV risk status
Gender
1.06 (0.61-1.85)
21/3174 (0.66)
26/4289 (0.61)
Female
0.63 (0.42-0.95)
50/5119 (0.98)
39/7239 (0.54)
<65 years
1.09 (0.70-1.71)
35/1983 (1.77)
44/2360 (1.86)
65 years
1.01 (0.51-2.00)
16/3609 (0.44)
19/5167 (0.37)
No
0.78 (0.56-1.09)
69/3493 (1.98)
64/4432 (1.44)
Yes
0.93 (0.66-1.30)
62/3836 (1.62)
66/4391 (1.50)
Studies 52 weeks
Age (years)
High CV risk status
ii) MACE in subgroup of long-term studies
MACE, major adverse cardiovascular events; M-H, Mantel-Haenszel, RR, risk ratio; CI, confidence interval; CV, cardiovascular
Adapted from: Mc Innes G, et al. Diabetes Obes Metab. 2015 Aug 7. doi: 10.1111/dom.12548. [Epub ahead of print]](https://image.slidesharecdn.com/cd3-240923084619-30364121/85/CD3-25-chon-thuoc-dtd-CD3-25-chon-thuoc-dtd-46-320.jpg)
![[CD6.52] Bao ve tim th畉n.pdf](https://cdn.slidesharecdn.com/ss_thumbnails/cd6-231001022337-55ff859e-thumbnail.jpg?width=560&fit=bounds)
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- 1. Ch畛n thu畛c 叩i th叩o 動畛ng t箪p 2 no trong i畛u tr畛 b畛nh tim m畉ch nguy c董 cao GS TS Tr畉n H畛u Dng Ch畛 t畛ch H畛i N畛i ti畉t - T Vi畛t Nam GAL SYM 151-01-06-17
- 2. S畛 l動畛ng b畛nh nh但n m畉c T tr棚n ton th畉 gi畛i v theo t畛ng v湛ng 畛a l箪 nm 2017 v 2045 (tu畛i 20 79) 叩i th叩o 動畛ng: V畉n 畛 s畛c kh畛e ton c畉u
- 3. S畛 ng動畛i m畉c b畛nh 叩i th叩o 動畛ng (20-79 tu畛i) 叩i th叩o 動畛ng tr棚n ton c畉u
- 4. a s畛 c叩c BN T typ 2 畛 ch但u kh担ng 畉t m畛c ti棚u HbA1c < 7.0% 1. Bryant W, et al. MJA 2006;185:3059. 2. Kosachunhanun N, et al. J Med Assoc Thai 2006;89:S66S71. 3. Lee WRW, et al. Singapore Med J 2001;42:5017. 4. Nagpal J & Bhartia A. Diabetes Care 2006;29:23418. 5. Soewondo P, et al. Med J Indoes 2010;19(4):23544. 6. Tong PCY, et al. Diab Res Clin Pract 2008;82:346352. 7. Pan C, et al. Curr Med Res Opin 2009;25:3945. 8. Choi YJ, et al. Diabetes Care 2009;32:201620. 9. Mafauzy M, et al. Med J Malaysia 2011;66(2):17581. Hong Kong (Diab Registry6) S. Korea (KNHANES8) 43.5% 56.5% Australia (St Vincents1) China (Diabcare7) 41.1% 58.9% India (DEDICOM4) 37. 8 37.8% 62.2% Thailand (Diab Registry2) 30.2% 69.8% Singapore (Diabcare3) 33.0% 67.0% 39.7% 60.3% 70.0% 30.0% 畉t m畛c ti棚u Kh担ng 畉t m畛c ti棚u 22.0% 78.0% Malaysia (DiabCare9) 32.1% 67.9% Indonesia (Diabcare5)
- 5. B畛nh V探ng M畉c Nguy棚n nh但n g但y m湛 hng 畉u B畛nh Th畉n Nguy棚n nh但n hng 畉u g但y suy th畉n G cu畛i (l畛c th畉n, gh辿p th畉n) B畛nh Tim M畉ch 畛t qu畛 T畛 l畛 b畛 畛t qu畛 v t畛 vong do b畛nh tim m畉ch tng 2 4 l畉n B畛nh Th畉n Kinh Nguy棚n nh但n hng 畉u g但y c畉t c畛t ch但n kh担ng do ch畉n th動董ng 8/10 BN T s畉 ch畉t do b畛nh tim m畉ch T type 2- CC BI畉N CH畛NG NGUY HI畛M 50% BN T typ 2 達 c坦 鱈t nh畉t 1 bi畉n ch畛ng khi 動畛c ch畉n o叩n
- 6. T Y畉u t畛 nguy c董 tim m畉ch m畉nh nh畉t 6
- 7. Di畛n ti畉n c畛a b畛nh 叩i th叩o 動畛ng t鱈p 2 Adapted from t鱈p 2 Diabetes BASICS. International Diabetes Center 2000 Ch畉n o叩n Insulin Glucose Ti畛n 叩i th叩o 動畛ng (IFG/IGT) NGT 叩i th叩o 動畛ng C叩c bi畉n ch畛ng m畉ch m叩u l畛n C叩c bi畉n ch畛ng m畉ch m叩u nh畛 R畛i lo畉n ch畛c nng t畉 bo 硫 動畛ng huy畉t sau n 動畛ng huy畉t 坦i 畛 kh叩ng insulin Ti畉t Insulin
- 8. 10 9 20 11 9 6 38 19 3* 30 Total CVD CHD Cardiac failure Intermittent claudication CVA Wilson PWF, Kannel WB. In: Hyperglycemia, Diabetes and Vascular Disease. Ruderman N et al, eds. Oxford; 1992. P<0.001 for all values except *P<0.05 Risk ratio Nam N畛 0 2 4 10 8 6 Age-adjusted Annual Rate/1000 叩i th叩o 動畛ng l nguy c董 c畛a bi畉n c畛 tim m畉ch CHD=Coronary heart disease, CVD=Cardiovascular disease Nghi棚n c畛u Framingham Heart : theo d探i 30 nm
- 9. B畛nh MV Coronary death Non-fatal MI Tai bi畉n m畉ch n達o Ischaemic stroke Haemorrhagic stroke Unclassified stroke B畛nh m畉ch m叩u kh叩c 2.00 (1.832.19) 2.31 (2.052.60) 1.82 (1.642.03) 2.27 (1.952.65) 1.56 (1.192.05) 1.84 (1.592.13) 1.73 (1.511.98) HR (95% CI) 26,505 11,556 14,741 3799 1183 4973 3826 Number of cases 1 1 2 4 Hazard ratio (diabetes vs no diabetes) Outcome T lm tng g畉p 担i bi畉n c畛 tim m畉ch Sarwar et al. Lancet 2010;375(9733):22152222. 2
- 10. AGE=Advanced glycation end products, CRP=C-reactive protein, CHD=Coronary heart disease HDL=High- density lipoprotein, HTN=Hypertension, IL-6=Interleukin-6, LDL=Low-density lipoprotein, PAI- 1=Plasminogen activator inhibitor-1, SAA=Serum amyloid A protein, TF=Tissue factor, TG=Triglycerides, tPA=Tissue plasminogen activator Subclinical Atherosclerosis Atherosclerotic Clinical Events Hyperglycemia AGE Oxidative stress Inflammation IL-6 CRP SAA Infection Defense mechanisms Pathogen burden Insulin Resistance HTN Endothelial dysfunction Dyslipidemia LDL TG HDL Thrombosis PAI-1 TF tPA Di畛n ti畉n b畛nh Biondi-Zoccai GGL et al. JACC 2003;41:1071-1077 C董 ch畉: T d畉n 畉n bi畉n c畛 tim m畉ch
- 11. Chu担i nguy c董 tim m畉ch 董 b畛nh nh但n T typ 2 Adapted from ADA. Diabetes Care. 2003;26:3160-3167. Tsao PS, et al. Arterioscler Thromb Vasc Biol. 1998;18:947-953. Hsueh WA, et al. Am J Med. 1998;105(1):4S-14S. ADA. Diabetes Care. 1998;21:310-314. Bi畉n ch畛ng Khuy畉t t畉t T畛 vong Kh叩ng insulin IGT Kh董i ph叩t T Nh畉y c畉m di truy畛n M担i tr動畛ng Dinh d動畛ng B辿o ph狸 t ho畉t 畛ng th畛 l畛c Tng H X董 v畛a M B/c th畉n kinh B/c th畉n B/c v探ng m畉c M湛 B畛nh m畉ch vnh Suy th畉n C畉t c畛t chi Triglycerides Tng insulin THA X董 v畛a 畛ng m畉ch Tng 動畛ng huy畉t KS H GIP GI畉M CC BI畉N C畛 V AN TON TIM M畉CH LUN L M畛T TRONG CC M畛C TIU C畛A CC NGHIN C畛U LM SNG
- 12. HbA1c Bi畉n ch畛ng vi m畉ch: BC th畉n, m湛 BC tim T畛 vong li棚n quan 畉n T 21% Stratton IM et al. UKPDS 35. BMJ 2000; 321: 405412 C畉t c畛t chi ho畉c b畛nh l箪 m畉ch ngo畉i vi kh担ng do ch畉n th動董ng 37% 14% 12% 43% 畛t qu畛 1% UKPDS: ch畛ng minh
- 15. K畉t c畛c tim m畉ch 畛 BN T typ 2 qua c叩c NC l但m sng Nghi棚n c畛u Th畛i gian m畉c T (TB) Thu畛c h畉 動畛ng huy畉ta Theo d探i (trung v畛) HbA1c: Ban 畉u, Kh叩c bi畛t gi畛a 2 nh叩nh BC vi m畉ch CVD T畛 vong UKPDS1 M畛i ch畉n o叩n SU/insulin ho畉c metformina so v畛i ch畉 畛 n 10 nm 7.1% (t畉t c畉 c叩c BN)b, 0.9%c UKPDS Long-term follow-up2 10 nm sau can thi畛p Kh担ng kh叩c bi畛t HbA1c gi畛a 2 nh叩nh Td ADVANCE3 8 nm KSH t鱈ch c畛c bao g畛m gliclazide so v畛i T th動畛ng quy 5 nm 7.5% (c畉 2 nh叩nh)b, 0.8%d ACCORD4,5 10 nm C叩c thu畛c T h畉 H 畛 c畉 2 nh叩nh 3.4 nm 8.1% (c畉 2 nh叩nh)e, 1.1%c VADT6 11.5 nm C叩c thu畛c T h畉 H 畛 c畉 2 nh叩nh 5.6 nm 9.4% ( c畉 2 nh叩nh)b, 1.5%d aObese patients; bMean baseline HbA1c; cMedian between-arm difference; dMean between-arm difference; eMedian baseline HbA1c. CV = cardiovascular; UKPDS = United Kingdom Prospective Diabetes Study (UKPDS); ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; ACCORD = Action to Control Cardiovascular Risk in Diabetes; VADT = Veterans Affairs Diabetes Trial. 1. UKPDS Group. Lancet. 1998;352:837853. 2. Holman RR et al. N Engl J Med. 2008;359:15771589. 3. ADVANCE Collaborative Group et al. N Engl J Med. 2008;358:2560 2572. 4. Gerstein HC et al. N Engl J Med. 2008;358:25452559. 5. Ismail-Beigi F et al. Lancet. 2010;376:419430. 6. Duckworth W et al. N Engl J Med. 2009;360:129139. Gi畉m HbA1c c坦 th畛 ph嘆ng ng畛a b畛nh m畉ch m叩u l畛n n畉u kh董i tr畛 s畛m, nh動ng hi畛u qu畉 c坦 th畛 kh担ng r探 trong kho畉ng th畛i gian r畉t di
- 16. VADT: N Engl J Med 2009;360:12939. Predictor HR p-value H畉 動畛ng huy畉t n畉ng 4.0 0.01 HbA1c 1.2 0.02 HDL 0.7 0.02 Tu畛i 2.1 <0.01 Ti畛n s畛 b畛nh tim m畉ch 3.1 <0.01 VADT: H畉 H n畉ng l y畉u t畛 d畛 b叩o ch鱈nh c畛a t畛 vong tim m畉ch
- 17. H畉U QU畉 TRN TIM M畉CH C畛A H畉 働畛NG HUY畉T VEGF IL-6 CRP Neutrophil activation Platelet activation Factor VIII Blood coagulation abnormalities Sympathoadrenal response Adrenaline Vi棚m Endothelial dysfunction Vasodilatation Heart rate variability Rhythm abnormalities Haemodynamic changes Heart workload Contractility Output H畉 働畛NG HUY畉T CRP, C-reactive protein; IL-6, interleukin 6; VEGF, vascular endothelial growth factor. Adapted from Desouza et al. Diabetes Care 2010;33:138994; Frier et al. Diabetes Care 2011;34(Suppl 2):S1327
- 18. Nguy c董 tim m畉ch tng l棚n 畛 c叩c BN c坦 c畉 T v b畛nh th畉n m畉n CHF, congestive heart failure; AMI, acute myocardial infarction; CVA/TIA, cerebrovascular accident/transient ischemic attack; PVD, peripheral vascular disease; ASVD, atherosclerotic vascular disease. *ASVD was defined as the first occurrence of AMI, CVA/TIA, or PVD. Foley RN, et al. J Am Soc Nephrol. 2005;16:489-495. x 2.8 x 2.3 x 1.7 x 2.1 x 2.0 x 2.5
- 19. Number of events More intensive Less intensive Difference in HbA1c (%) HR (95% CI) Stroke 378 370 -0.88 0.96 (0.83, 1.10) Myocardial infarction 730 745 -0.88 0.85 (0.76, 0.94) Hospitalisation for or death from heart failure 459 446 -0.88 1.00 (0.86, 1.16) Ph但n t鱈ch g畛p hi畛u qu畉 c畛a ki畛m so叩t H t鱈ch c畛c l棚n c叩c bi畉n c畛 tim m畉ch ch鱈nh, g畛m c畉 suy tim, 畛 BN T typ 2 Favours more intensive Favours less intensive Meta-analysis of 27,049 participants and 2370 major vascular events from: ADVANCE, UKPDS, ACCORD, VADT Turnbull FM et al. Diabetologia 2009;52:22882298 Nh動ng
- 20. Nh動ng t叩c 畛ng ti畛m 畉n l棚n bi畉n c畛 tim m畉ch c畛a c叩c nh坦m thu畛c i畛u tr畛 T Nh畛ng NC quan s叩t v ph但n t鱈ch g畛p: SU c坦 th畛 li棚n quan 畉n vi畛c tng nguy c董 bi畉n c畛 tim m畉ch, nh動ng ch動a c坦 c叩c NC th畛 nghi畛m l但m sng 畛 叩nh gi叩 t叩c 畛ng ti畛m 畉n ny1 C坦 nhi畛u b畉ng ch畛ng tr叩i ng動畛c v畛 畉nh h動畛ng tim m畉ch c畛a c叩c thu畛c nh坦m thiazolidinedione2,3 TZD b畛 ch畛ng ch畛 畛nh tr棚n suy tim 畛 III v IV4,5 C叩c ph但n t鱈ch g畛p g畉n 但y: i畛u tr畛 gi畉m H t鱈ch c畛c 畉nh h動畛ng kh担ng c坦 箪 ngh挑a th畛ng k棚 l棚n t畛 vong TM hay t畛 vong do m畛i nguy棚n nh但n, nh動ng c坦 th畛 li棚n quan 畉n gi畉m nguy c董 NMCT kh担ng t畛 vong6,7 1. Rao AD, et al. Diabetes Care. 2008;31:1672-1678; 2. Home PD, et al. Lancet. 2009;373:2125-2135; 3. Dormandy JA, et al. Lancet. 2005;366:1279- 1289; 4. Avandia [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; May 2011; 5. Actos [prescribing information]. Deerfield, IL: Takeda Pharmaceutical America, Inc.; July 2011; 6. Boussageon R, et al. BMJ. 2011;343:d4169; 7. Hemmingsen B, et al. BMJ. 2011;343:d6898.
- 21. C叩c thu畛c ki畛m so叩t H t叩c 畛ng l棚n c叩c c董 quan 鱈ch kh叩c nhau. Arnouts P et al. Nephrol. Dial. Transplant. 2013;ndt.gft462 息 The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
- 22. I畛U TR畛 T TP 2 Thu畛c ch畛n l畛a 畉u ti棚n metformin: ADA,AACE,IDF,EASD. Tuy nhi棚n, t畛 l畛 cao T t箪p 2 kh担ng 畉t 動畛c m畛c HbA1c mong mu畛n. Lo畉i thu畛c 畛 ngh畛 ti畉p theo:畛c ch畉 DPP-4, 畛ng v畉n GLP-1, sulfonylureas, glinides, TZD, 畛c ch畉 留 -glucosidase v insulin 董n tr畛 li畛u ho畉c k畉t h畛p.
- 23. Older Adults 26% of patients aged >65 have diabetes. Older adults have higher rates of premature death, functional disability & coexisting illnesses. At greater risk for polypharmacy, cognitive impairment, urinary incontinence, injurious falls & persistent pain. Screening for complications should be individualized and periodically revisited. At higher risk for depression American Diabetes Association Standards of Medical Care in Diabetes. Older adults. Diabetes Care 2017; 40 (Suppl. 1): S99-S104
- 24. T畛 l畛 h畉 動畛ng huy畉t c畛a c叩c SU *H畉 H: 動畛ng huy畉t mao m畉ch ng坦n tay 50 mg/dL (2.75 mmol/L) 1Glucovance [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2004. 2UKPDS Group. Lancet. 1998; 352: 837853. 3Draeger KE, et al. Horm Metab Res. 1996; 28: 419425. 4McGavin JK, et al. Drugs. 2002; 62; 13571364. 5Metaglip [package insert]. Princeton, NJ: Bristol-Myers Squibb Company, 2002. Sulfonylureas Glipizide5 Gliclazide4 Chlorpropamide2 Glyburide1 0 5 10 15 20 25 T畛 l畛 b畛 h畉 Hm畛i (%) 21.3% 15.3% 5% 2.9%* 14% 11% Glibenclamide3 Glimepiride3
- 25. BIOMEDICAL R 286 EPORTS 3: 284-288, 2015 Insulin & nguy c董 h畉 動畛ng huy畉t
- 26. Odds ratio 0 2 4 6 8 10 Placebo Sulfonylurea Basinsulin Inkretin -0.8% -0.9% -0.7% Placebo kontrollerad f旦r辰ndring i HbA1c Risk f旦r hypoglykemi Nguy c董 h畉 動畛ng huy畉t th畉p v畛i 畛c ch畉 DPP-4 叩nh gi叩 nguy c董 h畉 H 39 RCTs, n= 17 860, th畛i gian 12-52 tu畉n (trung b狸nh 28 tu畉n), HbA1c ban 畉u 7,3-9,9% Hi畛u qu畉 gi畉m HbA1c so placebo Liu et al., Diabetes Obes Metab 14:810, 2012
- 27. H畉U QU畉 C畛A H畉 働畛NG HUY畉T 1. Whitmer RA, et al. JAMA. 2009; 301: 15651572; 2. Bonds DE, et al. BMJ. 2010; 340: b4909; 3. Barnett AH. Curr Med Res Opin. 2010; 26: 13331342; 4. J旦nsson L, et al. Value Health. 2006; 9: 193198; 5. Foley JE, Jordan J. Vasc Health Risk Manag. 2010; 6: 5. 41548; 6. Begg IS, et al. Can J Diabetes. 2003; 27: 128140; 7. McEwan P, et al. Diabetes Obes Metab. 2010; 12: 431436. H畉 働畛NG HUY畉T C叩c bi畉n ch畛ng tim m畉ch3 Gi畉m c但n do gi畉m n 5 H担n m棚3 Tng nguy c董 Tai n畉n giao th担ng6 Tng chi ph鱈 N畉m vi畛n4 Gi畉m nh畉n th畛c3 Tng nguy c董 畛ng kinh 3 T畛 vong2,3 Tng nguy c董 m畉t tr鱈 nh畛1 Gi畉m ch畉t l動畛ng cu畛c s畛ng7
- 28. Strictly Confidential. Proprietary information of Novartis. For internal use ONLY. March 2010. GAL10.497. Novartis.
- 29. Nguy c董 c畛a ki畛m so叩t 動畛ng m叩u t鱈ch c畛c 畛 ng動畛i cao tu畛i H畉 動畛ng m叩u S畛 d畛ng nhi畛u thu畛c T動董ng t叩c thu畛c Thu畛c t動董ng t叩c v畛i c叩c b畛nh hi畛n c坦
- 30. 30
- 31. 31
- 32. 32 Ph動董ng th畛c t叩c d畛ng c畛a GLP-1 畛 ng動畛i GLP-1 動畛c ti畉t ra 畛 tb L c畛a ru畛t Theo 坦 K.t ti畉t insulin ph畛 thu畛c glucose 畛c ch畉 ti畉t glucagon Lm ch畉m v董i d畉 dy T叩c d畛ng l但u di 動畛c ch畛ng minh tr棚n s炭c v畉t Tng kh畛i l動畛ng tb beta v duy tr狸 ho畉t 畛ng tb beta C畉i thi畛n s畛 nh畉y c畉m insulin 畛c ch畉 s畛 ngon mi畛ng L炭c th畛c n 動畛c h畉p thu Drucker DJ. Curr Pharm Des 2001; 7:1399-1412 Drucker DJ. Mol Endocrinol 2003; 17:161-171
- 33. 33 N畛ng 畛 GLP-1 huy畉t t動董ng gi畉m 30% 畛 b畛nh nh但n T typ 2
- 34. 34 Hi畛u 畛ng incretin tr棚n ng動畛i b狸nh th動畛ng 3 Adapted from a review article on the actions and effects of incretin hormones. Adapted from Drucker DJ. Cell Metab. 2006; 3:153-6. Ph坦ng th鱈ch Insulin
- 35. 35 3 Ph坦ng th鱈ch Insulin Hi畛u 畛ng incretin tr棚n ng動畛i T t箪p 2 Adapted from a review article on the actions and effects of incretin hormones. Adapted from Drucker DJ. Cell Metab. 2006; 3:153-6.
- 36. 36 GLP-1 nhanh ch坦ng b畛 gi叩ng h坦a b畛i men DPP-4 36 Adapted from a review article on the actions and effects of incretin hormones. Drucker DJ et al. Diabetes Care 2007;30:1335-43.
- 37. 37 C叩c thu畛c l畛p 畛c ch畉 men DPP-4: GLIPTIN SITA SAXA VILDA LINA
- 38. 38 畛c ch畉 DPP4 lm tng n畛ng 畛 GLP-1 c畛a BN T t箪p 2 Meal * * * * * * * * * * * * GLP-1=glucagon-like peptide-1; T2DM=type 2 diabetes mellitus. Vildagliptin 100 mg once daily is not an approved dose *P <0.05 Balas B, et al. J Clin Endocrinol Metab 2007;92:124955 0 4 8 12 16 17:00 20:00 23:00 02:00 05:00 08:00 Time Active GLP-1 (pmol/L) * Vildagliptin 100 mg (n=16) Placebo (n=16)
- 39. 39 Vildagliptin 50 mg hai l畉n/ngy + metformin (n=137) Ahr辿n et al. Diabetes Care 33:730, 2010 Glimepiride 畉n 6 mg m畛t l畉n/ngy + metformin (n=121) 8.0 4.0 0.0 4.0 AUC 2 gi畛 (n畛n ~55 pmol/l/gi畛) Thay 畛i glucagon sau b畛a n sau 2 nm i畛u tr畛 Gi畉m glucagon sau n : T叩c 畛ng kh叩c bi畛t c畛a 畛c ch畉 DPP4 so v畛i SU
- 40. Ph但n t鱈ch g畛p v畛 hi畛u qu畉 ki畛m so叩t 動畛ng huy畉t c畛a nh坦m 畛c ch畉 DPP4 (1)
- 41. 41 Hi畛u qu畉 ki畛m so叩t HbA1c c畛a nh坦m 畛c ch畉 DPP4 Clinical Therapeutics/Volume 34, Number 6, 2012 41
- 42. 42 Hi畛u qu畉 ki畛m so叩t H 坦i c畛a nh坦m 畛c ch畉 DPP4 42 Clinical Therapeutics/Volume 34, Number 6, 2012
- 43. HbA1c b畉t 畉u >8% Trung b狸nh ~8.4% BMI b畉t 畉u >30 kg/m2 Trung b狸nh ~7.3% HbA1c Change from Baseline (%) b畛nh nh但n >65 years Trung b狸nh ~7.3% n = 149 169 658 626 276 265 Th棚m vo i畛u tr畛 Metformin (TB ~1.9 g/ngy) Glimepiride li畛u t畛i 6 mg 1 l畉n/ng + metformin VILDAGLIPTIN 50 mg 2 l畉n/ng + metformin Th畛i gian: 52 tu畉n Th棚m vo met: vilda vs glim BL=baseline; BMI=body mass index; glim=glimepiride; HbA1c=hemoglobin A1c; met=metformin; T2DM=type 2 diabetes mellitus; vilda=GalvusMet Per protocol population. Ferrannini E, et al. Diabetes Obes Metab. 2008; Epub ahead of print. Data on file, Novartis harmaceuticals, LAF237A2308 52-week interim analysis. Ph畛i h畛p 畛c ch畉 DPP4 v畛i Metformin: Hi畛u qu畉 t動董ng 動董ng Met + SU trong ki畛m so叩t 動畛ng huy畉t
- 44. 44 Gi畉m bi畉n c畛 h畉 H khi ph畛i h畛p 畛c ch畉 DPP4 + metformin glim=glimepiride; met=metformin; vilda=vildagliptin. 1T鱈nh an ton trong d但n s畛. 2theo quy tr狸nh ban 畉u. aB畉t k畛 c董n no c畉n gi炭p 畛 c畛a ng動畛i kh叩c. Th畛i gian: 104 tu畉n Th棚m vo met: vilda vs glim Matthews DR, et al. Diabetes Obes Metab. 2010; 12: 780789. 59 838 0 100 200 300 400 500 600 700 800 900 2,3 18,2 0 4 8 12 16 20 T畛 l畛 m畛i m畉c (%) B畛nh nh但n c坦 1 c董n (%) 1553 1546 n = S畛 c叩c bi畉n c畛 S畛 l動畛ng c叩c bi畉n c畛 h畉 動畛ng huy畉t 1553 1546 n = 0 15 0 2 4 6 8 10 12 14 16 S畛 c叩c bi畉n c畛 S畛 l動畛ng h畉 動畛ng huy畉t n畉nga 1553 1546 n = 0 13 0 2 4 6 8 10 12 14 16 Ng動ng thu畛c do h畉 動畛ng huy畉t 1553 1546 n = S畛 c叩c bi畉n c畛 HbA1c trung b狸nh2 Thay 畛i trung b狸nh c坦 hi畛u ch畛nh HbA1c t動董ng 動董ng nhau gi畛a i畛u tr畛 vildagliptin v glimepiride : 0.1% (0.0%) cho c畉 hai M畛c ti棚u ch鱈nh kh担ng k辿m h董n 達 畉t 動畛c : 97.5% CI -0.00, 0.17; gi畛i h畉n tr棚n 0.3% Vildagliptin 50 mg 2 l畉n m畛i ngy+ metformin Glimepiride 畉n 6 mg 1 l畉n/ngy + metformin H畉 動畛ng huy畉t1
- 45. 45 T鱈nh an ton tr棚n tim m畉ch c畛a nh坦m 畛c ch畉 DPP4 (ph但n t鱈ch g畛p t畛 c叩c nghi棚n c畛u pha II & III) Diabetes Care 2016;39(Suppl. 2):S196S204 | DOI: 10.2337/dcS15-3024 HR < 1 : nh坦m 畛c ch畉 DPP4 an ton tr棚n tim m畉ch
- 46. 46 Vildagliptin kh担ng lm tng nguy c董 & t畛 l畛 m畛i m畉c c叩c bi畉n c畛 tim m畉ch ch鱈nh (MACE) 畛 ng動畛i cao tu畛i > 65 tu畛i Vildagliptin n/N (%) Comparators n/N (%) M-H RR (95% CI) 0.74 (0.52-1.05) 64/3928 (1.63) 57/5310 (1.07) Male 0. 1 1.0 10.0 100.0 0.01 Vildagliptin better Comparator better i) MACE in subgroups by age, gender, and CV risk status Gender 1.06 (0.61-1.85) 21/3174 (0.66) 26/4289 (0.61) Female 0.63 (0.42-0.95) 50/5119 (0.98) 39/7239 (0.54) <65 years 1.09 (0.70-1.71) 35/1983 (1.77) 44/2360 (1.86) 65 years 1.01 (0.51-2.00) 16/3609 (0.44) 19/5167 (0.37) No 0.78 (0.56-1.09) 69/3493 (1.98) 64/4432 (1.44) Yes 0.93 (0.66-1.30) 62/3836 (1.62) 66/4391 (1.50) Studies 52 weeks Age (years) High CV risk status ii) MACE in subgroup of long-term studies MACE, major adverse cardiovascular events; M-H, Mantel-Haenszel, RR, risk ratio; CI, confidence interval; CV, cardiovascular Adapted from: Mc Innes G, et al. Diabetes Obes Metab. 2015 Aug 7. doi: 10.1111/dom.12548. [Epub ahead of print]
- 47. 47 Tr棚n b畛nh nh但n l畛n tu畛i Vildagliptin l li畛u ph叩p duy nh畉t hi畛n nay c坦 th畛 d湛ng 畛 b畛nh nh但n l畛n tu畛i (> 75 tu畛i) 1 1Galvus速 (vildagliptin) Summary of Product Characteristics, Feb 2012; 2Januvia速 (sitagliptin) Summary of Product Characteristics, Jan 2012; 3Onglyza速 (saxagliptin) Summary of Product Characteristics, Jan 2012; 4Victoza速 (liraglutide) Summary of Product Characteristics, Dec 2011; 5Byetta速 (exenatide) injection Summary of Product Characteristics, Sep 2011. Th担ng tin tr棚n nh達n h畛p thu畛c cho b畛nh nh但n l畛n tu畛i Vildagliptin: Kh担ng c畉n i畛u ch畛nh li畛u 畛 b畛nh nh但n l畛n tu畛i 1 Sitagliptin: Kh担ng c畉n ch畛nh li畛u theo tu畛i. D畛 li畛u an ton hi畛n nay 畛 b畛nh nh但n 75 tu畛i c嘆n h畉n ch畉 v n棚n c畉n tr畛ng khi s畛 d畛ng. Saxagliptin: Kinh nghi畛m s畛 d畛ng cho b畛nh nh但n 75 tu畛i c嘆n r畉t h畉n ch畉 v n棚n c畉n tr畛ng khi i畛u tr畛 cho nh坦m b畛nh nh但n ny3 Liraglutide: 畛 ng動畛i gi (>65 tu畛i): Kh担ng c畉n ch畛nh li畛u theo tu畛i. Kinh nghi畛m s畛 d畛ng cho b畛nh nh但n 75 tu畛i c嘆n h畉n ch畉 4 Exenatide: N棚n th畉n tr畛ng khi d湛ng & vi畛c tng li畛u t畛 5 亮g l棚n 10 亮g n棚n ti畉n hnh d竪 d畉t 畛 b畛nh nh但n >70 tu畛i. Kinh nghi畛m l但m sng BN >75 tu畛i c嘆n h畉n ch畉
- 48. 48 Vildagliptin 鱈t nguy c董 t動董ng t叩c thu畛c1 Vildagliptin kh担ng chuy畛n h坦a qua cytochrome P450 1; y畉u t畛 quan tr畛ng 畛 nh畛ng b畛nh nh但n ang d湛ng nhi畛u thu畛c Nghi棚n c畛u tr棚n ng動畛i kh畛e m畉nh cho th畉y vildagliptin kh担ng t動董ng t叩c v畛i digoxin (c董 ch畉t c畛a Pgp), warfarin (c董 ch畉t c畛a CYP2C9), amlodipine, ramipril, valsartan hay simvastatin1 1. Th担ng tin k棚 toa 達 動畛c ng k箪. Vildagliptin: nguy c董 t動董ng t叩c thu畛c th畉p
- 49. 49 Chi ph鱈 Hi畛u qu畉 gi畉m HbA1c t h畉 動畛ng huy畉t t t叩c d畛ng ph畛 t/kh担ng tng c但n C董 s畛 l畛a ch畛n theo ADA/EASD
- 50. ADA 2019
- 51. 51
- 52. 52 52 K畉t lu畉n Ki畛m so叩t t畛t 動畛ng huy畉t l m畛c ti棚u b畛nh nh但n T tr叩nh g但y c董n h畉 H n畉ng. L畛a ch畛n ph畛i h畛p thu畛c theo ti棚u ch鱈 Hi畛u qu畉, an ton v 董n gi畉n 畛c ch畉 DDP-4 l m畛t ch畛n l畛a ph畛i h畛p thu畛c c坦 hi畛u qu畉 ki畛m so叩t H t畛t, 鱈t h畉 動畛ng huy畉t, d湛ng 動畛c cho nhi畛u 畛i t動董ng v k畉t h畛p 動畛c v畛i nhi畛u nh坦m thu畛c, V畛i Vildagliptin l thu畛c 達 動畛c th畛c nghi畛m t畛t tr棚n 畛i t動畛ng 75t . Vildagliptin kh担ng lm tng nguy c董 & t畛 l畛 m畛i m畉c c叩c bi畉n c畛 tim m畉ch ch鱈nh (MACE) 畛 ng動畛i cao tu畛i > 65 tu畛i
- 53. 53 C叩m 董n s畛 l畉ng nghe