Achieving Glycemic Control Without Therapeutic Compromise: The Role of JANUVIA (sitagliptin) A Novel DPP-4 Inhibitor for Type 2 Diabetes 1
Overview I. Type 2 Diabetes Pathophysiology II. Background on incretin hormones III. A New Novel Treatment Approach - Enhancing Incretin through DPP-4 Inhibition 2
The Pathophysiology of Type 2 Diabetes Includes Three Main Defects Insulin deficiency Islet Pancreas Alpha cell produces excess glucagon Beta cell produces less insulin Excess glucagon Diminished insulin Liver Diminished insulin Hyperglycemia Muscle and fat Excess glucose output Insulin resistance (decreased glucose uptake) Adapted from Buse JB et al. In Williams Textbook of Endocrinology. 1th ed. Philadelphia, Saunders, 23:1427 1483; Buchanan TA Clin Ther 23;25(suppl B):B32 B46; Powers AC. In: Harrison s Principles of Internal Medicine. 16th ed. New York: McGraw-Hill, 25:2152 218; Rhodes CJ Science 25;37:38 384. 3
Glucagon (µµg/ml) Insulin (µu/ml) Glucose (mg/1 ml) Insulin and Glucagon Response to a Large Carbohydrate Meal in Type 2 Diabetes 36 33 3 27 24 11 8 15 12 9 6 3 14 13 12 11 1 9 Type 2 diabetes mellitus (n=12)* Nondiabetic controls (n=11) 6 Meal Depressed/delayed insulin response Nonsuppressed glucagon 6 12 18 24 *Insulin measured in five patients Adapted from Müller WA et al N Engl J Med 197;283:19 115. Time (minutes) 4
Adjusted incidence per 1 person years (%) UKPDS: 改善 HbA 1c 控制可減少糖尿病相關併發症發生 16 Incidence of Complications N=4585 每下降 1% HbA 1c Relative Risk N=3642 風險降低 (P<.1) 14 12 Any diabetes endpoint Microvascular endpoint Myocardial infarcation Diabetesrelated deaths 1 8 6 4 1% Myocardial infarctions Microvascular complications 2 5 6 7 8 9 1 11 Mean HbA 1c (%) Amputations or deaths from peripheral vascular disorders Data adjusted for age, sex, and ethnic group, expressed for white men aged 5 54 years at diagnosis and with mean duration of diabetes of 1 years. Adapted with permission from Stratton IM et al. UKPDS 35. BMJ 2;321:45 412. 5
HOMA % sensitivity HOMA % beta Belfast Diet Study Beta-Cell Function Declined While Insulin Sensitivity Remained Stable in Type 2 Diabetes 6 Insulin sensitivity 8 Beta-cell function 4 6 4 2 2 2 4 6 2 4 6 Years from diagnosis Years from diagnosis Data from the first six years of 1-year follow-up of the Belfast Diet Study: Data from 67 newly diagnosed subjects with type 2 diabetes mellitus (N=432) who required oral antihyperglycemic therapy or insulin due to secondary failure of diet therapy during years 5 to 7 HOMA=Homeostasis Model Assessment; data expressed as percentages of values in lean nondiabetic reference population Adapted from Levy J et al Diabet Med 1998;15:29 296. 6
Beta-cell function (%) HbA 1c (%) UKPDS 16 Declining Beta-Cell Function Was Associated with Increasing Hyperglycemia 1 1 75 9 8 5 7 25 Diet/conventional therapy (n=11) Metformin (n=159) Sulfonylurea (n=511) 1 2 3 4 5 6 6 5 Diet/conventional therapy (n=297) Metformin (n=251) Insulin or sulfonylurea (n=695) 1 2 3 4 5 6 Years Years Beta-cell function assessed by HOMA HbA 1c results shown from obese patients UKPDS=United Kingdom Prospective Diabetes Study; HbA 1c =glycosylated hemoglobin Adapted from UKPDS Group Diabetes 1995;44:1249 1258. 7
Overview I. Type 2 Diabetes Pathophysiology II. Background on incretin hormones III. A New Novel Treatment Approach - Enhancing Incretin through DPP-4 Inhibition 8
INCRETIN 紀元 - 超過百年研發史 192: Bayliss&Starling 第一次發現小腸分泌某種物質能刺激胰臟分泌 1932:La Barre 採用 INCRETIN 一字, 來形容來自腸道且可增加胰臟內分泌的荷爾蒙 1964: 觀察到口服與 IV 葡萄糖引起 insulin 分泌程度不同, 即所謂 incretin effect 1973: 發現 GIP 是一種人類 incretin 1986:T2DM 的 incretin effect 比正常人弱 1987: 發現 GLP-1 亦為人類 incretin 1995: 發現 DPP-4 酵素會分解 GIP GLP-1 2~: 開始研究 DPP-4 抑制劑及類 incretin 物質的臨床治療應用 25: 第一個 incretin mimetics(glp-1 agonist): Exenatide 在美國上市 26: 第一個 DPP-4 inhibitor: Sitagliptin 在美國上市 9
Incretin( 腸泌素 ; 腸促胰素 ) 透過對胰島的作用來維持生理正常血糖衡定 攝食 腸道 從腸道細胞分泌經由血液到胰臟 Incretins: GLP-1 (L-cells ileum/colon) GIP (K-cells duodenum) 胰臟 β-cells α-cells 具葡萄糖依存性的 Insulin from beta cells (GLP-1 and GIP) Glucagon from alpha cells (GLP-1) 具葡萄糖依存性的 Insulin increases peripheral glucose uptake insulin and glucagon reduce hepatic glucose output 生理血糖控制 Adapted from Brubaker PL, Drucker DJ Endocrinology 24;145:2653 2659; Zander M et al Lancet 22;359:824 83; Ahrén B Curr Diab Rep 23;3:365 372; Buse JB et al. In Williams Textbook of Endocrinology. 1th ed. Philadelphia, Saunders, 23:1427 1483. 1
GLP-1 and GIP Are the Two Major Incretins GLP-1 Secreted by L-cells in the distal gut (ileum and colon) Stimulates glucose-dependent insulin release Suppresses hepatic glucose output by inhibiting glucagon secretion in a glucose-dependent manner Enhances beta-cell proliferation and survival in animal models and isolated human islets GIP Secreted by K-cells in the proximal gut (duodenum) Stimulates glucosedependent insulin release Enhances beta-cell proliferation and survival in islet cell lines GLP-1=glucagon-like peptide 1; GIP=glucose-dependent insulinotropic polypeptide Adapted from Drucker DJ Diabetes Care 23;26:2929 294; Ahrén B Curr Diab Rep 23;3:365 372; Drucker DJ Gastroenterology 22;122: 531 544; Farilla L et al Endocrinology 23;144:5149 5158; Trümper A et al Mol Endocrinol 21;15:1559 157; Trümper A et al J Endocrinol 22;174:233 246. 11
IR Insulin, mu/l IR Insulin, mu/l Incretin Effect( 腸泌素作用 ) 是重要生理血糖調控機制, 而 T2DM 的 Incretin 作用較差 Control Subjects (n=8) Patients With Type 2 Diabetes (n=14) 8 Normal Incretin Effect.6 8 Diminished Incretin Effect.6.5.5 6.4 6.4 4 2 7%.3.2.1 nmol/l 4 2 3%.3.2.1 nmol/l 6 12 Time, min 18 Oral glucose load IR = immunoreactive Adapted with permission from Nauck M et al. Diabetologia 1986;29:46 52. Copyright 1986 Springer-Verlag. Vilsbø ll T, Holst JJ. Diabetologia 24;47:357 366. 6 12 Time, min Intravenous (IV) glucose infusion 18 12
Summary of Trials: GLP-1 and GIP Levels and Actions in Type 2 Diabetes Patients with type 2 diabetes mellitus Incretin levels Incretin actions GLP-1 (p<.5 vs. NGT) Intact GIP Intact* (p=.47 vs. NGT) *When corrected for gender and BMI Adapted from Toft-Nielsen M-B et al J Clin Endocrinol Metab 21;86:3717 3723; Nauck MA et al J Clin Invest 1993;91:31 37. 13
Glucagon (pmol/l) Insulin (pmol/l) Glucose (mg/dl) T2DM: GLP-1 具葡萄糖依存性的降血糖效果 27 225 18 135 9 * * * * * * * Placebo GLP-1 infusion 25 2 15 1 5 2 15 1 5 Infusion * * * * * * * * * * * * With hyperglycemia GLP-1 stimulated insulin and suppressed glucagon. When glucose levels approached normal, insulin levels declined and glucagon was no longer suppressed. Time (minutes) N=1 patients with type 2 diabetes. Patients were studied on two occasions. A regular meal and drug schedule was allowed for one day between the experiments with GLP-1 and placebo. *p<.5 GLP-1 vs. placebo Adapted from Nauck MA et al Diabetologia 1993;36:741 744. 6 12 18 24 14
DPP-4 抑制劑可增加 incretin 濃度而強化了 T2DM 既有的血糖調控能力 進食 腸道 腸道細胞分泌 incretin 胰臟 β-cells α-cells 具葡萄糖依存性的 Insulin from beta cells (GLP-1 and GIP) Insulin increases peripheral glucose uptake 強化生理既有的血糖調控能力高血糖症 DPP-4 Inhibitor X DPP-4 Enzyme Inactive incretins Glucagon from alpha cells (GLP-1) 具葡萄糖依存性的 DPP-4 = dipeptidyl peptidase 4 insulin and glucagon reduce hepatic glucose output Adapted from Brubaker PL, Drucker DJ Endocrinology 24;145:2653 2659; Zander M et al Lancet 22;359:824 83; Ahrén B Curr Diab Rep 23;3:365 372; Buse JB et al. In Williams Textbook of Endocrinology. 1th ed. Philadelphia, Saunders, 23:1427 1483. 15
Overview I. Type 2 Diabetes Pathophysiology II. Background on incretin hormones III. A New Novel Treatment Approach - Enhancing Incretin through DPP-4 Inhibition 16
品名 JANUVIA( 佳糖維 ) F F F NH 2 O N N N N CF 3 唯一同時在各先進國家及台灣上市的口服 DPP-4 抑制劑藥物 26/1 美國 FDA 核准上市 27/3 歐盟核准上市 ( 英 法 德 北歐等國 ) 27/7 台灣核准上市 強效且高度選擇性抑制 DPP-4 酵素作用的治療第 2 型糖尿病藥物 全球超過二百萬張的處方 17
Sitagliptin Is Potent and Highly Selective (>25x) for the DPP-4 Enzyme Enzyme IC 5 (nm) DPP-4 18 DPP-8 48, DPP-9 >1, DPP-2, DPP-7, >1, FAP >1, PEP >1, APP >1, Herman et al. ADA. 24. 18
% Plasma DPP IV inhibition PK/PD Study on Health Volunteer 口服 1 mg QD JANUVIA 可全天候抑制 >8% 的 DPP-4 酵素活性 1 8 6 4 Placebo Sitagliptin (1 mg qd) F F F NH 2 O N N N N F F F 2 4 8 12 16 2 24 Time (hr) Bergman et al. Clin Ther 26;28:55-72. 19
GLP-1 (pg/ml) GIP (pg/ml) Crossover study in patients with T2DM 口服一劑 Sitagliptin 可維持 24hr 作用讓口服葡萄 糖後之具活性型 GLP-1 & GIP 濃度增加為兩倍 Placebo 4 Active GLP-1 OGTT 2 hrs (n=55) OGTT 24 hrs (n=19) 9 OGTT 2 hrs (n=55) Active GIP OGTT 24 hrs (n=19) Sitagliptin 25 mg Sitagliptin 2 mg 35 3 25 2 15 1 5 2-fold increase in active GLP-1 p<.1 vs placebo 8 7 6 5 4 3 2 1 2-fold increase in active GIP p<.1 vs placebo 2 4 6 24 26 28 2 4 6 24 26 28 Hours Postdose Hours Postdose Herman GA et al. Clin Pharmacol Ther 25;78:675-88. 2
pg/ml mciu/ml 4 3 2 1 口服一劑 Sitagliptin 就可有效在血糖過高時增加胰島素分泌 抑制升糖素及降血糖效果 75 Crossover Study in Patients with T2DM Insulin 分泌增加 Drug Dose Glucose load 21-22% AUC p<.5 for both dose comparisons to placebo for AUC 1 2 3 4 Glucagon 分泌受抑制 32 28 24 2 血糖降低 Drug Dose Glucose load Placebo Sitagliptin 25 mg Sitagliptin 2 mg AUC 22-26% 7 65 6 55 7-14% AUC 16 12 p<.1 for both dose comparisons to placebo for AUC 1 2 3 4 5 6 Time (hours) 5 p<.5 for both dose comparisons to placebo for AUC 1 2 3 4 Time (hours) Herman GA et al. J Clin Endocrinol Metab 26;91:4612-9. 21
Glucose (mg/dl) at wk 4 Add-on Therapy to Metformin Study 使用 JANUVIA : 增加全天候的血糖控制功效空腹與飯後血糖均同時獲得改善 24 22 2 18 Breakfast Lunch Dinner Dose 1 7:3 Dose 2 18:3 Metformin 15 mg/day + placebo (n=13) Sitagliptin 5 mg BID + metformin 15 mg/day (n=13) Treatment difference: 32.8 mg/dl (P<.1)* 16 14 12 1 8: Day 1 13: 19: : Day 2 7:3 *Least-squares mean difference in weighted mean glucose To convert mg/dl to mmol/l; divide by 18. Adapted from Brazg R et al. Diabetes Obes Metab. 27;9:186 193. 22
DPP-4 Inhibition by Sitagliptin Restores the Islet Cell Mass Ratios and Function! (in T2DM mice) Diabetic mice Control mice Diabetic mice + sitagliptin Diabetic mice + SU Green: Insulin-producing β-cell Red: Glucagon-producing α-cell Adapted from Mu J et al. Poster presentation at the 67th Scientific Session of the ADA, June 27. 23
JANUVIA 在各臨床試驗中一致展 現優異的降血糖效果 單方治療 (P21, P23, A21) 現行口服藥物治療 metformin, TZD, SU 者合併 JANUVIA 治療 (P19, P2, P35, P53) 與 Sulfonylurea head-to-head 比較研究 (P24) 初始合併 metformin 治療 (P36) 24
A1C (%) A1C (%) A1C (%) JANUVIA 單方初始治療在臨床試驗中一致展現優異的 HbA 1C 降低效果 change vs = placebo* 8.4 18 周研究 1 -.6% (p<.1) 8.4 24 周研究 2 -.79% (p<.1) 8.4 Japanese 研究 3-1.5% (p<.1) 8. 8. 8. 7.6 7.6 7.6 7.2 7.2 Placebo (n=74) Sitagliptin 1 mg (n=168) 7.2 Placebo (n=244) Sitagliptin 1 mg (n=229) 6.8 Placebo (n=75) Sitagliptin 1 mg (n=75) 6 12 18 Time (weeks) 5 1 15 2 25 Time (weeks) 4 8 12 Time (weeks) *between group difference in LS means Adapted from 1. Raz I et al. Diabetologia. 26;49:2564-71. PN23; 2. Schneer P et al. Diabetes Care. 26;29:2632-7. PN21; 3. Nonaka K et al; A21. Nonaka K et al. Dabetes Research and Clinical Practice 27 (in press). 25
LSM change from baseline (pmol/l/pmol/l) LSM change from baseline (%) 24-week, Monotherapy, Placebo-controlled Study JANUVIA improves measures of β-cell function Proinsulin/insulin ratio HOMA-β -.2 n=22 2 16 P.1 Placebo Sitagliptin 1 mg/day n=218 -.4 12 -.6 8 -.8 n=21 4 n=235 -.1 P.1 Mean Baseline (pmol/l/pmol/l): Sitagliptin 1 mg/day=.47 Placebo=.44 Mean Baseline (%): Sitagliptin 1 mg/day=57.6 Placebo=55.8 All-patients-as-treated population; HOMA-β = homeostasis model assessment-β Adapted from Aschner et al. Diabetes Care. 26;29:2632 2637. 26
HbA 1c (% ± SE) 7.8 7.6 7.4 Add-on Sitagliptin With Metformin a vs Sulfonylurea b With Metformin Study 在原先用 Metformin 的病人 : 合併 JANUVIA vs. 合併 Sulfonylurea (52 周 ) 1. 長達一年穩定控制效果 2. 效果與 SU 相當 LS mean change from baseline (for both groups):.67% 7.2 7. 6.8 6.6 6.4 6.2 6. Sulfonylurea + metformin (n=411) Sitagliptin + metformin (n=382) Achieved primary hypothesis of noninferiority to sulfonylurea 5.8 6 12 18 24 3 36 42 52 Weeks a Sitagliptin (1 mg/day) with metformin ( 15 mg/day); b Specifically glipizide Per-protocol population; LS = least squares Adapted from Nauck et al. Diabetes Obes Metab. 27;9:194 25. 27
Change from baseline in HbA 1c (%) Add-on Sitagliptin With Metformin a vs Sulfonylurea b With Metformin Study JANUVIA 在基準值愈高者 HbA 1C 降幅愈大. -.2 -.4 -.6 -.8-1. -1.2-1.4-1.6-1.8-2. n = n=117 依 HbA 1C 基礎值分組 <7% 7 to <8% 8 to <9% 9% 117 112 179 167 82 82 33 21 -.14 -.26 -.59 Sitagliptin + metformin Sulfonylurea + metformin -.53-1.11-1.13-1.76 a Sitagliptin (1 mg/day) with metformin ( 15 mg/day); b Specifically glipizide can be tirated up to 2 mg. Per-protocol population -1.68 Adapted from Nauck et al. Diabetes Obes Metab. 27;9:194 25. 28
Body weight (kg ± SE) % of patients with one episode Add-on Sitagliptin With Metformin a vs Sulfonylurea b With Metformin Study Metformin 合併 JANUVIA 使體重下降 (vs.su 體重上升 ) 且低血糖症發生率也較 SU 低 3 2 體重隨時間的平均值變化 c Sulfonylurea + metformin (n=416) Sitagliptin + metformin (n=389) 5 4 低血糖症 c 32% 1 3 P<.1-1 -1.5 Kg 2 1 5% 減少 85% 發生 -2-3 12 24 38 52 Weeks Week 52 Sulfonylurea + metformin (n=584) Sitagliptin + metformin (n=588) a Sitagliptin (1 mg/day) with metformin ( 15 mg/day); b Specifically glipizide; c all-patients-as-treated population Least squares mean between-group difference at Week 52 (95% CI): change in body weight = 2.5 kg [ 3.1, 2.] (P<.1); Least squares mean change from baseline at Week 52: glipizide: +1.1 kg; sitagliptin: 1.5 kg (P<.1) Adapted from Nauck et al. Diabetes Obes Metab. 27;9:194 25. 29
一開始就合併 JANUVIA + Metformin Mean baseline A1C 8.8% 提供優越的 HbA 1C 降低功效 Metformin Sitagliptin 1 mg q.d. 5 mg b.i.d. 1 mg b.i.d. Sitagliptin and Metformin 5 mg / 5 mg b.i.d. 5 mg / 1 mg b.i.d. -.5 -.8% A1C (%) -1-1.5 -.6% -1.% -1.3% -1.6% -2 -.8% -2.1% -2.5 Monotherapy Treatment Groups Combination Treatment Groups *Placebo-subtracted LS mean change from baseline at Week 24. Adapted from Goldstein BJ et al. Diabetes Care 27;3:1979-87 3
HbA 1c (% mean ± SE) Sitagliptin With Metformin Coadministration Initial Therapy Study Coadministration of Sitagliptin With Metformin Reduced HbA 1c by 2.9% in Patients With Mean Baseline HbA 1c of 11.2% In the prespecified open-label cohort, patients (n=117) with HbA 1c >11% or fasting glucose >28 mg/dl were treated with sitagliptin with metformin (5/1 mg BID) 11.5 11. 1.5 1. Δ -2.9% 9.5 9. 8.5 8. 7.5 Sitagliptin 5 mg + metformin 1 mg BID (n=111) 6 12 18 24 Weeks Mean HbA 1c reduction from baseline by 3.5% for the completers population (n/n=87/111) Adapted from Goldstein BJ et al. Diabetes Care 27;3:1979-87. 31
FPG (mg/dl ± mean SE) Sitagliptin With Metformin Coadministration Initial Therapy Study Coadministration of Sitagliptin With Metformin Reduced FPG by 127 mg/dl in Patients With Mean Baseline FPG of 314 mg/dl In the prespecified open-label cohort, patients (n=117) with HbA 1c >11% or fasting glucose >28 mg/dl were treated with sitagliptin with metformin (5/1 mg BID) 34 32 3 28 26 24 22 2 18 Δ -127 mg/dl 16 14 Sitagliptin 5 mg + metformin 1 mg BID (n=111) 3 6 9 12 15 18 21 24 Weeks Adapted from Goldstein BJ et al. Diabetes Care 27;3:1979-87. 32
27 ACE/AACE Road Map to Achieve Glycemia Goal: Naïve to Therapy Adapted from ACE/AACE Diabetes Road Map Task Force. Endocrine Practice 27; 13:261-9. 33
27 ACE/AACE Road Map to Achieve Glycemia Goal: Treated Patients Adapted from ACE/AACE Diabetes Road Map Task Force. Endocrine Practice 27; 13:261-9. 34
Sitagliptin 在降低 HbA 1C 的同時既不增加低血糖風險 體重亦不增加 低血糖發生率 Placebo Sitagliptin 1 mg q.d. Sitaglitpin 2 mg q.d. Patients with hypoglycemia (%).9% 1.2%.9% 體重變化 Pooled Phase III Population Analysis: no statistically significant difference in incidence for either dose vs placebo Neutral effect on body weight In monotherapy studies, small decreases from baseline (~.1 to.7 kg) with sitagliptin; slightly greater reductions with placebo (~.7 to 1.1 kg) In combination studies, weight changes with sitagliptin similar to placebo-treated patients 35
安全性與耐受性狀況 Pre-specified Pooled Phase III analysis, including monotherapy and combination studies: over 15 patients on sitagliptin and over 75 patients on placebo Summary measures of adverse experiences (AEs) were similar to placebo Including overall clinical AEs, serious AEs, discontinuations due to AEs, drug-related AEs, laboratory AE summary measures Small differences in incidence of specific AEs specific AE (nasopharyngitis 1.2% difference) AEs with at least 3% incidence and Numerically Higher in Sitagliptin than Placebo Group Placebo (N = 778) % % Sitagliptin 1 mg (N = 182) Difference vs Pbo (95% CI) Upper Respiratory Tract Infection 6.7 6.8.1 (-2.3, 2.4) Headache 3.6 3.6 Nasopharyngitis 3.3 4.5 1.2 (-.7, 3.) Diarrhea 2.3 3..7 (-.9, 2.2) Recommended dose in label: 1 mg q.d. 36
JANUVIA - 寬廣使用的適應症 核准適應症 第 2 型糖尿病 劑量與用法 JANUVIA 的建議劑量為每日一次 1 公絲, 不須 titration 可單獨使用或可與 metformin sulfonylurea PPARγ 作用劑 ( 如 : TZD) 合併使用 JANUVIA 可和食物併用, 亦可不和食物併用 不需監測肝功能 肝腎功能不全皆可使用 ( 腎功能不全者需調整劑量 ) 無臨床重要性的藥物交互作用 當 JANUVIA 無法避免 sulfonylurea 所引發的低血糖症, 當併用時可能必須考慮使用較低劑量的 sulfonylurea, 以降低 sulfonylurea 引發低血糖的風險 37
Sitagliptin 特殊族群使用 腎功能不全者中度腎功能不全 (CCr = 3-5 ml/min): 5 mg QD 重度腎功能不全 (CCr <3 ml/min) 及 ESRD/ 洗腎病患 :25 mg QD 肝功能不全者輕中度肝功能不全者, 不須調整劑量在重度肝功能不全 (Child-Pugh 分數 >9) 患者方面, 目前尚無任何臨床經驗 不過, 由於 sitagliptin 主要乃是透過腎臟排出體外, 因此一般並不認為嚴重的肝功能不全會影響 sitagliptin 的藥物動力學 小兒 : 未進行相關研究 懷孕 : B 級 38
http://www.januvia.com.tw http://www.incretin.com.tw 39
Summary -- Role of JANUVIA in T2DM Therapy 1. 國內第一也是目前唯一 DPP-4 inhibitor, 可提昇 incretin 濃度, 而強化 T2DM 生理既有血糖調控能力 2. JANUVIA 可增加活化態的 Incretins 濃度, 在血糖升高時作用, 使 β 細胞製造及分泌更多胰島素及抑制 α 細胞分泌昇糖素 3. JANUVIA 在各種 HbA 1C 基礎值的病患, 不論是單一使用 或與其他藥物合併使用, 皆可提供優異的降血糖功效 4. JANUVIA 可改善 細胞功能數值, 達到更持久的血糖控制, 延緩糖尿病患者需增加其他口服糖尿病用藥或注射胰島素可能性 5. JANUVIA 的安全性及耐受性與安慰劑類似 可改善病患遵醫囑性, 幫助患者持續用藥提升積極控制血糖的信心 6. 使用 JANUVIA 並無因投與 PPARγ agonist, insulin 或 SU 而產生的體重增加的副作用, 進而降低與體重增加有關的危險性 7. 使用 JANUVIA 低血糖的機率與安慰類似 8. JANUVIA 可用於肝 腎功能不全及老年患者 ( 中重度腎功能不良患者需降低劑量 ) 4
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