JP2006515625A - 前糖尿病患者および2型糖尿病患者における心血管系の罹病率および死亡率を低下させるための長時間作用型インスリン - Google Patents
前糖尿病患者および2型糖尿病患者における心血管系の罹病率および死亡率を低下させるための長時間作用型インスリン Download PDFInfo
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Abstract
Description
2型糖尿病(DM)患者では、冠心疾患、心血管系疾患および末梢血管の疾患を包含するアテローム性動脈硬化症のリスクが増大している。糖尿病それ自体(1)ならびに正確な糖尿病ではないが異常脂質血症、高血圧症および肥満の関連危険因子が、このリスクの主要部分に寄与している。とくに、高血糖のレベルが鍵となる役割を果たしている。一方微小血管の併発症に対する血中グルコースの上昇の関係はよく認識されている(7−9)が、そのアテローム発生過程に対する関係は、最近まで十分には証明されていなかった。フィンランドにおける2型DMの中年齢および高年齢患者集団を基盤とする予測試験では、ベースライン空腹時血中グルコース(FBG)またはHbA1cと冠心疾患による死亡率との間に直線性の相関が示されている(10)。WESDRデータベースには、年齢30歳またはそれ以上で、糖尿病と診断された対象において、グリコシル化ヘモグロビンの1%の上昇毎に血管性の原因による死亡率は統計学的に有意に増大し、様々なタイプの事象について危険率は1.10〜1.28であった(11)。Islington Diabetes Surveyでは食後2時間のグルコースまたはHbA1cと冠心疾患の間には直線性の相関が見出され、2−時間グルコース試験ではさらに強い関連が見出されている(12)。San Antonio Heart Studyにおいては、高血糖レベルはすべての原因および心血管系の死亡率の強力な、独立の予測因子であった(13)。
下は統計学的に有意ではなかったが、これは全体的に試験サイズが小さかったこと(n=110)によるものと考えられる。現在、幾つかの大きな予測試験が、心血管系の危険因子を有する患者における糖尿病の処置は心血管系の罹病率および死亡率を低下させるという仮説を、とくに一次的に評価するため、ACCORD試験(NHLBI)およびVA糖尿病試験を含めて進行中または計画中である。
・ DPP試験におけるIGTのメトフォルミン(metformin)による処置では2型DMへの進行速度が統計的に有意な31%の低下を伴って認められた(21)。
・ STOP-NIDDM試験において、アカルボーゼ(acarbose)はIGTから2型DMへの進行を、プラセボアームでの41.8%から3.6年間の平均処置期間に32.8%に低下させ(p<0.05)、同時にCV事象のリスクを49%まで低下させた(40)。
・ 中断されたTRIPOD試験において、妊娠前糖尿病を有する対象群中プラセボ処置群の12.3%に対し、トログリタゾン(troglitazone)処置群では5.4%(p<0.05)が、平均30ヶ月にわたる処置で2型DMを発症した(45)。
‐VLDL合成の低下、およびリポ蛋白パターンの改善(トリグリセライドの低下、HDL−Cの上昇)
‐β細胞レベルおよびインスリン標的組織における脂質毒性の低下
‐虚血心筋における不可欠酸化的代謝の低下
〇脂肪組織におけるホルモン感受性リパーゼの抑制不全、これは脂質分解の増大および、とくに肝臓によるVLDL−トリグリセライド(TG)の合成のための脂肪細胞からのFFAの供給増加を招く
〇TGに富む粒子(たとえばVLDL)の異化の低下、およびそれらの粒子の表面成分のHDLへの移行の低下、これはDDL中に認められる低いHDL−Cレベルの一部を説明する
HDLから他のリポ蛋白へのコレステロールの移行の加速、これがHDL−Cの低下に寄与する
●カイロミクロンおよびさらにアテローム発生性の残余のカイロミクロンのクリアランスの低下、ならびに他の残余粒子(中間密度のリポ蛋白もしくはIDL)のクリアランスの低下
●リポ蛋白リパーゼ(LPL)および肝TGリパーゼ(HTGL)の活性低下、これは熱量のための筋肉および肥満細胞におけるTGのFFAへの分解である
●肝臓によるVLDLの過剰産生、これがグルコースおよびFFAの上昇によって増悪される
●インスリンは注射によって投与しなければならず、多くの患者は注射に不快を感じる
●インスリンおよび注射は後期の段階の汚名を受けさせ、―「もし私がインスリンを投与されていれば、私の糖尿病はとても重症に違いない」―そしてインスリンの先送りは「私の糖尿病はまだそれ程ひどくない」という具合である。
1.Lantus(登録商標)の投与から得られる明瞭なピークのない24−時間血漿インスリンプロフィルは、他のインスリン製剤では歴史的に1日の間の予測できない時間に予測できない程度で起った過剰のインスリン濃度によって患者が蒙る害を低下させる。
1)スクリーニング前少なくとも10週間薬理学的な処置を受けておらず(寝たきりではない)、グリコヘモグロビンは検査室の正常上限の<150%(たとえば、上限が6%であれば<9%)、または
2)OADの1種(スルホニル尿素、ビグアナイド、チアゾリジンジオン、α−グルコシダーゼ阻害剤)の安定した用量をスクリーニングの時点で少なくとも10週間投与され(または入院加療の前10週間、同定されればCV事象のために入院)、この投与が最大用量の半量以上であれば、グリコヘモグロビンは検査室の正常上限の<133%(たとえば上限が6%であれば<8%)であり、この投与が最大用量の半量未満であれば、グリコヘモグロビンは検査室の正常上限の<142%(たとえば、上限が6%であれば<8.5%)である。
1. Stamler J,Vaccaro 0, Norton JD, WentworthD. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993; 16: 434-44.
2. Stratton IM, Adler AI, Nell A W, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321:405-412.
3. Coutinho M, Wang Y, Gerstein HC,Yusuf S. The relationship between glucose and incident cardiovascular events. Diabetes Care 1999; 22 (2): 233-240.
4. Khaw K-T, Wareham N, Luben R, Bingham S, Oakes S, Welch A, et al. Glycated haemoglobin, diabetes, and mortality in men in the Norfolk cohort of European Prospective Investigation of Cancer and Nutrition (EPIC-Norfolk). BMJ 2001 ; 322: 15-18.
5. Gerstein HC, Yusuf S. Dysglycaemia and risk of cardiovascular disease. Lancet 1996; 347: 949-50.
6. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997; 20 (7):1183-97.
7. The Diabetes Control and Complications Trial Research Group: the effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993 ; 329: 977-86.
8. Shichiri M, Kishikawa H ,Ohkubo Y, Wake N. Long-term results of the Kumamoto study on optimal diabetes control in type 2 diabetic patients. Diabetes Care 2000 Apr; 23 (Supp2):B21-9.
9. Reichard P, Nilsson B-Y, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med 1993 ; 329: 304-9.
10. Laakso M. Glycemic control and the risk for coronary heart disease in patients with non-insulin-dependent diabetes mellitus. Annals Int Med 1996 ; 124 (1 pt2) :127-130.
11. Moss SE, Klein R, Klein BEK, Meuer SM. The association of glycemia and cause-specific mortality in a diabetic population. Arch Int Med 1994 ; 154: 2473-9.
12. Jackson CA, Yudkin JS, Forrest RD. A comparison of the relationships of the glucose tolerance test and theglycated haemoglobin assay with diabetic vascular disease in thecornmlmity. The Islington Diabetes Survey. Diabetes Res Clin Pract 1992; 17: 111-123.
13. Wei M, Gaskill SP, Haffner SM, Stern MP. Effects of diabetes and level of glycemia on all-cause and cardiovascular mortality. The San Antonio Heart Study.
Diabetes Care 1998; 21 (7): 1167-72.
14. UKPDS Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes(UKPDS 33). Lancet 1998; 352: 837-53.
15. deVegt F, Dekker JM, Ruhe HG, Stehouwer CDA, NijpelsG, Bouter LM, et al.
Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study. Diabetologia 1999; 42:926-931.
16. Simmons LA, McCallurn J, Friedlander Y,Simmons J. Fasting plasma glucose in non-diabetic elderly women predicts increased all-cause mortality and coronary heart disease risk. Aust NZ Med 2000; 30: 41-7.
17. Bjomholt JV, Nitter-Hauge S, ErikssenG, JervellJ, AaserE, Erikssen J, et al. Fasting blood glucose: an underestimated risk factor for cardiovascular death. Diabetes Care 1999; 22: 45-9.
18. Balkau B, Shipley M, Jarret RJ, Pyorala K, Pyorala M, Forhan A. et al. High blood glucose concentration is a risk factor for mortality in middle-aged nondiabetic men. 20-year follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study. Diabetes Care 1998; 21: 360-367.
19. Balkau B, Bertrais S, Dugimetiere P, Eschwege E. Is there a glycemic threshold for mortality risk? Diabetes Care 1999; 22 (5): 696-9.
20. Barzilay JI, Spiekennan CF, Wahl PW, Kuller LH, Cushrnan M, Furberg CD, et
al. Cardiovascular disease in older adults with glucose disorders: comparison of American Diabetes Association criteria for diabetes mellitus with WHO criteria. Lancet 1999; 354: 622-5.
21. Diabetes Prevention Research Group : Reduction in the evidence of Type 2 Diabetes with life-style intervention or metformin. N EnglJ Med 346: 393-403, 2002.
22. Passikivi J, Walberg F. Preventive tolbutamide treatment and arterial disease in mild hyperglycaemia. Diabetologia 1971; 7: 323-27.
23. Sartor G, Schersten B,Carlstrorn S, Melander A, Norden A, Persson G. Ten-year follow-up of subjects with impaired glucose tolerance. Prevention of diabetes by tolbutamide and diet regulation. Diabetes 1980; 29: 41-49.
24. Malmberg K, Ryden L, Hamsten A, HerlitzI, Waldenstrom A, Wedel H. Mortality prediction in diabetic patients with myocardial infarction: experiences from the DIGAMI study. Cardiovascular Research 1997; 34: 248-253.
25. Van den BergheG, Wouters P, Weekers F, Verwaest C,Bruyninckx F, Schetz M et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001 ; 345: 1359-67.
26. Baron AD. Vascular reactivity. Am I Cardiol 1999 ; 84(lA) : 25J-27J.
27. Aljada A, Dandona P. Effect of insulin on human aortic endothelial nitric oxide synthase. Metabolism 2000; 49: 147-50.
28. Taylor PD, Oon BB, Thomas CR, Poston T, Poston L. Prevention by insulin treatment of endothelial dysfunction but not enhanced noradrenaline-induced contractility in mesenteric resistance arteries from streptozotocin-induced diabetic rats. Br J Pharmacol 1994; 111 (1): 35-41.
29. Dandona P, Aljada A, Mohanty P, Ghanim H, Hamouda W, Assian E, Ahmad S. Insulin inhibits intranuclear nuclear factor kB and stimulates IkB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect? J Clin Endocrin; July 2001; 3257-3265.
30. American Diabetes Association: Clinical Practice Recommendations. Position Statement, Diabetes Mellitus and Exercise. Diabetes Care 2001 24(Suppl 1) :551-5
31. Diabetes Prevention Research Group: Reduction in the evidence of Type 2 Diabetes with life-style intervention or metformin. N Engl J Med 346: 393-403,2002.
32. Diabetes Prevention Research Group: Reduction in the evidence of Type 2 Diabetes with life-style intervention ormetformin. N Engl J Med 346: 393-403, 2002.
33. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H,Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M; Finnish Diabetes Prevention Study Group.
(Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland. jaakko. tuomilehto @; ktl)
Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3; 344 (18): 1343-50.
34. Murray FT, Zinman B, McLean PA, DeNoga A, Albisser AM, Leibel BS, et. al. The metabolic response to moderate exercise in diabetic man receiving intravenous and subcutaneous insulin. Journal of Clinical Endocrinology and Metabolism 1977 4: 708-720
35. Herz M, Profozic V, Arora V, Smircik-Duvnjac L, Kovacevic I, Boras J et al. Effects of a fixed mixture of 25% insulin lispro and 75% NPL on plasma glucose during and after moderate physical exercise in patients with type 2 diabetes. Current medical research and opinions 2002 18: 188-93
36. Rabasa-Lhoret R, Bourque J, Ducros F, Chiasson, J-L. Guidelines for premeal insulin dose reduction for postprandial exercise of different intensities and durations in type 1 diabetic subjects treated intensively with a basal-bolus insulin regimen (ultralente-lispro). Diabetes Care 2001 24: 625-30
37. Hernandez JM, Moccia T, Fluckey JD, Ulbrecht JS, Farrell PA. Fluid snacks to help persons with type 1 diabetes avoid late postexercise hypoglycemia. Medicine and Science in Sports and Exercise 2000 32: 904-10.
38. Riddle M, Rosenstock J, Gerich J. The Treat-to-Target trial. Diabetes Care
2003 26:
39. Lepore M, Pampanelli S, Fanelli C, Porcellati F, Bartocci L, DiVince
nzo A et al. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and human ultralente insulin, and continouous subcutaneous infusion of insulin lispro. Diabetes 2000 49: 2142-8.
40. Chiasson J-L, Josse RG, Gomis R, Hanefeld M,Karasik A, Laakso M. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with Impaired Glucose Tolerance. JAMA 2003 290: 486-94
41. Cryer P, Davis s, Shamoon H. Hypoglycemia in diabetes. Diabetes Care 2003 26: 1902-12
42. The UKPDS Research Group. A 6-year, m randomized, controlled trial comparing sulfonylurea, insulin, andmetformin therapy in patients with newly-diagnosed type 2 diabetes that could not be controlled with diet therapy. Ann Int Med 1998 128 : 165-75
43. Taddei S, Virdis A, Mattei P, Natali A, Ferrannini E, Salvetti A. Effect of insulin on acetylcholine-induced vasodilation in normotensive subjects and patients with essential hypertension. Circulation 1995 ; 92:2911-2918.
44. Rask-Madsen C, Ihlemann N, Krarup T, Christiansen E, Kober L, Nervil KC, Torp Pedersen C. Insulin therapy improves insulin-stimulated endothelial function in patients with Type II diabetes and ischemic heart disease. Diabetes. 2001; 50:2611-2618.
45. Azen SP, Peters RK, Berkowitz K, Kjos S, Xiang A, Buchanan TA.
(Department of Medicine, University of Southern California (USC) School of Medicine 90033, USA.)
TRIPOD(TRoglitazone In the Prevention Of Diabetes): a randomized, placebo-controlled trial of troglitazone in women with prior gestational diabetes mellitus; Control Clin Trials. 1998 Apr ; 19 (2): 217-31.
Claims (58)
- 長時間作用型インスリンの有効量を投与することからなる患者のIGTを処置する方法。
- 長時間作用型インスリンはインスリングラルギンである請求項1記載の方法。
- 有効量は1日あたり約2〜約150 IUの範囲である請求項2記載の方法。
- 有効量は1日あたり約2〜約80 IUの範囲である請求項3記載の方法。
- 有効量は1日あたり約2〜約40 IUの範囲である請求項4記載の方法。
- 患者は以前の心筋梗塞、卒中、虚血性の変化が証明されているアンギナ、以前の冠動脈、頚動脈もしくは末梢動脈の血管新生、または心電図もしくは心エコー図による左心室の肥大からなる群より選択される1またはそれ以上の、以前の重篤な心血管系事象の既往を有する請求項2記載の方法。
- 患者は以前の心筋梗塞、卒中、虚血性の変化が証明されているアンギナ、以前の冠動脈、頚動脈もしくは末梢動脈の血管新生、または心電図もしくは心エコー図による左心室の肥大からなる群より選択される1またはそれ以上の有意な心血管系危険因子を有する請求項2記載の方法。
- 長時間作用型インスリンの有効量を投与することからなる患者のIFGを処置する方法。
- 長時間作用型インスリンはインスリングラルギンである請求項8記載の方法。
- 有効量は1日あたり約2〜約150 IUの範囲である請求項9記載の方法。
- 有効量は1日あたり約2〜約80 IUの範囲である請求項10記載の方法。
- 有効量は1日あたり約2〜約40 IUの範囲である請求項11記載の方法。
- 患者は以前の心筋梗塞、卒中、虚血性の変化が証明されているアンギナ、以前の冠動脈、頚動脈もしくは末梢動脈の血管新生、または心電図もしくは心エコー図による左心室の肥大からなる群より選択される1またはそれ以上の、以前の重篤な心血管系事象の既往を有する請求項9記載の方法。
- 患者は以前の心筋梗塞、卒中、虚血性の変化が証明されているアンギナ、以前の冠動脈、頚動脈もしくは末梢動脈の血管新生、または心電図もしくは心エコー図による左心室の肥大からなる群より選択される1またはそれ以上の有意な心血管系危険因子を有する請求項9記載の方法。
- 長時間作用型インスリンの有効量を投与することからなる初期の2型糖尿病患者を処置する方法。
- 長時間作用型インスリンはインスリングラルギンである請求項15記載の方法。
- 有効量は1日あたり約2〜約150 IUの範囲である請求項16記載の方法。
- 有効量は1日あたり約2〜約80 IUの範囲である請求項17記載の方法。
- 有効量は1日あたり約2〜約40 IUの範囲である請求項18記載の方法。
- 患者は以前の心筋梗塞、卒中、虚血性の変化が証明されているアンギナ、以前の冠動脈、頚動脈もしくは末梢動脈の血管新生、または心電図もしくは心エコー図による左心室の肥大からなる群より選択される1またはそれ以上の、以前の重篤な心血管系事象の既往を有する請求項16記載の方法。
- 患者は以前の心筋梗塞、卒中、虚血性の変化が証明されているアンギナ、以前の冠動脈、頚動脈もしくは末梢動脈の血管新生、または心電図もしくは心エコー図による左心室の肥大からなる群より選択される1またはそれ以上の有意な心血管系危険因子を有する請求項16記載の方法。
- 長時間作用型インスリンの有効量を投与することからなる2型糖尿病患者における糖尿病性異常脂質血症を処置する方法。
- 長時間作用型インスリンはインスリングラルギンである請求項22記載の方法。
- 有効量は1日あたり約2〜約150 IUの範囲である請求項23記載の方法。
- 有効量は1日あたり約2〜約80 IUの範囲である請求項24記載の方法。
- 有効量は1日あたり約2〜約40 IUの範囲である請求項25記載の方法。
- 2型糖尿病患者は以前、食事および/または運動のみで処置されていた請求項23記載の方法。
- 2型糖尿病患者は薬物にナイーブである請求項23記載の方法。
- 長時間作用型インスリンの有効量を投与することからなる、IFG、IGT、初期2型糖尿病または2型糖尿病からなる群より選択される疾患または状態と診断された患者におけるアテローム性動脈硬化症を処置する方法。
- 長時間作用型インスリンはインスリングラルギンである請求項29記載の方法。
- 有効量は1日あたり約2〜約150 IUの範囲である請求項30記載の方法。
- 有効量は1日あたり約2〜約80 IUの範囲である請求項31記載の方法。
- 有効量は1日あたり約2〜約40 IUの範囲である請求項32記載の方法。
- 長時間作用型インスリンの有効量を投与することからなる、IFG、IGT、初期2型糖尿病または2型糖尿病からなる群より選択される疾患または状態と診断された患者における内皮機能を改善する方法。
- 長時間作用型インスリンはインスリングラルギンである請求項34記載の方法。
- 有効量は1日あたり約2〜約150 IUの範囲である請求項35記載の方法。
- 有効量は1日あたり約2〜約80 IUの範囲である請求項36記載の方法。
- 有効量は1日あたり約2〜約40 IUの範囲である請求項37記載の方法。
- 長時間作用型インスリンの有効量を投与することからなる、IFG、IGT、初期2型糖尿病または2型糖尿病からなる群より選択される疾患または状態と診断された患者における左心室質量の増大を防止する方法。
- 長時間作用型インスリンはインスリングラルギンである請求項39記載の方法。
- 有効量は1日あたり約2〜約150 IUの範囲である請求項40記載の方法。
- 有効量は1日あたり約2〜約80 IUの範囲である請求項41記載の方法。
- 有効量は1日あたり約2〜約40 IUの範囲である請求項42記載の方法。
- 長時間作用型インスリンの有効量を投与することからなる、IFG、IGT、初期2型糖尿病または2型糖尿病からなる群より選択される疾患または状態と診断された患者における左心室の拡張または収縮機能を改善する方法。
- 長時間作用型インスリンはインスリングラルギンである請求項44記載の方法。
- 有効量は1日あたり約2〜約150 IUの範囲である請求項45記載の方法。
- 有効量は1日あたり約2〜約80 IUの範囲である請求項46記載の方法。
- 有効量は1日あたり約2〜約40 IUの範囲である請求項47記載の方法。
- 長時間作用型インスリンの有効量を投与することからなる、IFG、IGT、初期2型糖尿病または2型糖尿病からなる群より選択される疾患または状態と診断された患者における血中グルコースレベルを低下させる方法。
- 長時間作用型インスリンはインスリングラルギンである請求項49記載の方法。
- 有効量は1日あたり約2〜約150 IUの範囲である請求項50記載の方法。
- 有効量は1日あたり約2〜約80 IUの範囲である請求項51記載の方法。
- 有効量は1日あたり約2〜約40 IUの範囲である請求項52記載の方法。
- 長時間作用型インスリンの有効量を投与することからなる、IFG、IGT、初期2型糖尿病または2型糖尿病からなる群より選択される疾患または状態と診断された患者における頚動脈の内厚の増大を防止する方法。
- 長時間作用型インスリンはインスリングラルギンである請求項54記載の方法。
- 有効量は1日あたり約2〜約150 IUの範囲である請求項55記載の方法。
- 有効量は1日あたり約2〜約80 IUの範囲である請求項56記載の方法。
- 有効量は1日あたり約2〜約40 IUの範囲である請求項57記載の方法。
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015512908A (ja) * | 2012-03-28 | 2015-04-30 | サノフイ | 基礎インスリン療法 |
JP2019505503A (ja) * | 2015-12-23 | 2019-02-28 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 心臓の代謝性に対するランタスの効果 |
Families Citing this family (55)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9006175B2 (en) | 1999-06-29 | 2015-04-14 | Mannkind Corporation | Potentiation of glucose elimination |
ATE385193T1 (de) | 2002-03-20 | 2008-02-15 | Mannkind Corp | Inhalationsgerät |
ES2328579T3 (es) * | 2003-07-25 | 2009-11-16 | Conjuchem Biotechnologies Inc. | Derivados de insulina de larga duracion y procedimientos asociados. |
AU2005277208B2 (en) | 2004-08-20 | 2011-11-24 | Mannkind Corporation | Catalysis of diketopiperazine synthesis |
DK1791542T3 (en) | 2004-08-23 | 2015-06-15 | Mannkind Corp | Diketopiperazinsalte for pharmaceutical delivery |
BRPI0615819B8 (pt) | 2005-09-14 | 2021-05-25 | Mannkind Corp | processo para preparar uma composição de distribuição de fármaco compreendendo um agente ativo e uma micropartícula fumaril dicetopiperazina cristalina. |
CN101389348A (zh) | 2006-02-22 | 2009-03-18 | 曼金德公司 | 用于改善包含二酮哌嗪和活性剂的微粒的药物性质的方法 |
CA3086027C (en) | 2008-06-13 | 2022-05-17 | Mannkind Corporation | A dry powder inhaler and system for drug delivery |
US8485180B2 (en) | 2008-06-13 | 2013-07-16 | Mannkind Corporation | Dry powder drug delivery system |
MX2010014240A (es) | 2008-06-20 | 2011-03-25 | Mankind Corp | Un metodo y aparato interactivo para perfilar en tiempo real esfuerzos de inhalacion. |
TWI532497B (zh) | 2008-08-11 | 2016-05-11 | 曼凱公司 | 超快起作用胰島素之用途 |
CA3016451A1 (en) | 2008-10-17 | 2010-04-22 | Sanofi-Aventis Deutschland Gmbh | Combination of an insulin and a glp-1 agonist |
US9117015B2 (en) | 2008-12-23 | 2015-08-25 | Roche Diagnostics Operations, Inc. | Management method and system for implementation, execution, data collection, and data analysis of a structured collection procedure which runs on a collection device |
US20120011125A1 (en) | 2008-12-23 | 2012-01-12 | Roche Diagnostics Operations, Inc. | Management method and system for implementation, execution, data collection, and data analysis of a structured collection procedure which runs on a collection device |
US10437962B2 (en) | 2008-12-23 | 2019-10-08 | Roche Diabetes Care Inc | Status reporting of a structured collection procedure |
US9659037B2 (en) | 2008-12-23 | 2017-05-23 | Roche Diabetes Care, Inc. | Management method and system for implementation, execution, data collection, and data analysis of a structured collection procedure which runs on a collection device |
US9918635B2 (en) | 2008-12-23 | 2018-03-20 | Roche Diabetes Care, Inc. | Systems and methods for optimizing insulin dosage |
US10456036B2 (en) | 2008-12-23 | 2019-10-29 | Roche Diabetes Care, Inc. | Structured tailoring |
US8849458B2 (en) * | 2008-12-23 | 2014-09-30 | Roche Diagnostics Operations, Inc. | Collection device with selective display of test results, method and computer program product thereof |
US8314106B2 (en) | 2008-12-29 | 2012-11-20 | Mannkind Corporation | Substituted diketopiperazine analogs for use as drug delivery agents |
DK2405963T3 (da) | 2009-03-11 | 2013-12-16 | Mannkind Corp | Apparat, system og fremgangsmåde til at måle modstand i en inhalator |
WO2010144789A2 (en) | 2009-06-12 | 2010-12-16 | Mannkind Corporation | Diketopiperazine microparticles with defined specific surface areas |
WO2011056889A1 (en) | 2009-11-03 | 2011-05-12 | Mannkind Corporation | An apparatus and method for simulating inhalation efforts |
KR101772372B1 (ko) | 2009-11-13 | 2017-08-29 | 사노피-아벤티스 도이칠란트 게엠베하 | Glp-1 효능제 및 메티오닌을 포함하는 약제학적 조성물 |
RU2537239C2 (ru) | 2009-11-13 | 2014-12-27 | Санофи-Авентис Дойчланд Гмбх | Фармацевтическая композиция, включающая агонист glp-1, инсулин и метионин |
AU2011202239C1 (en) | 2010-05-19 | 2017-03-16 | Sanofi | Long-acting formulations of insulins |
US8532933B2 (en) | 2010-06-18 | 2013-09-10 | Roche Diagnostics Operations, Inc. | Insulin optimization systems and testing methods with adjusted exit criterion accounting for system noise associated with biomarkers |
KR20130117755A (ko) | 2010-06-21 | 2013-10-28 | 맨카인드 코포레이션 | 건조 분말 약물 운반 시스템 및 방법 |
HUE031181T2 (en) | 2010-08-30 | 2017-06-28 | Sanofi Aventis Deutschland | Use of AVE0010 for the manufacture of a medicament for the treatment of type 2 diabetes |
US20120173151A1 (en) | 2010-12-29 | 2012-07-05 | Roche Diagnostics Operations, Inc. | Methods of assessing diabetes treatment protocols based on protocol complexity levels and patient proficiency levels |
WO2012135765A2 (en) | 2011-04-01 | 2012-10-04 | Mannkind Corporation | Blister package for pharmaceutical cartridges |
US9821032B2 (en) | 2011-05-13 | 2017-11-21 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin |
US8755938B2 (en) | 2011-05-13 | 2014-06-17 | Roche Diagnostics Operations, Inc. | Systems and methods for handling unacceptable values in structured collection protocols |
US8766803B2 (en) | 2011-05-13 | 2014-07-01 | Roche Diagnostics Operations, Inc. | Dynamic data collection |
WO2012174472A1 (en) | 2011-06-17 | 2012-12-20 | Mannkind Corporation | High capacity diketopiperazine microparticles |
SI2750699T1 (sl) | 2011-08-29 | 2015-11-30 | Sanofi-Aventis Deutschland Gmbh | Farmacevtska kombinacija, za uporabo pri glikemični kontroli pri pacientih, ki imajo sladkorno bolezen tipa 2 |
TWI559929B (en) | 2011-09-01 | 2016-12-01 | Sanofi Aventis Deutschland | Pharmaceutical composition for use in the treatment of a neurodegenerative disease |
MX2014004983A (es) | 2011-10-24 | 2014-09-22 | Mannkid Corp | Metodos y composiciones para tratar dolor. |
EP2785366A1 (en) * | 2011-12-01 | 2014-10-08 | Sanofi | Insulin glargine versus metformin for the first-line treatment of early type 2 diabetes |
CN104619369B (zh) | 2012-07-12 | 2018-01-30 | 曼金德公司 | 干粉药物输送系统和方法 |
EP2911690A1 (en) | 2012-10-26 | 2015-09-02 | MannKind Corporation | Inhalable influenza vaccine compositions and methods |
WO2014144895A1 (en) | 2013-03-15 | 2014-09-18 | Mannkind Corporation | Microcrystalline diketopiperazine compositions and methods |
JP6457484B2 (ja) | 2013-04-03 | 2019-01-23 | サノフイSanofi | インスリンの長時間作用型製剤による糖尿病の治療 |
JP6491658B2 (ja) | 2013-07-18 | 2019-03-27 | マンカインド コーポレイション | 熱安定性乾燥粉末医薬組成物及び方法 |
US11446127B2 (en) | 2013-08-05 | 2022-09-20 | Mannkind Corporation | Insufflation apparatus and methods |
WO2015148905A1 (en) | 2014-03-28 | 2015-10-01 | Mannkind Corporation | Use of ultrarapid acting insulin |
WO2016001185A1 (en) * | 2014-07-02 | 2016-01-07 | Novo Nordisk A/S | Dosage regimen for the treatment of diabetes |
US10561806B2 (en) | 2014-10-02 | 2020-02-18 | Mannkind Corporation | Mouthpiece cover for an inhaler |
HRP20230470T1 (hr) | 2014-12-12 | 2023-07-21 | Sanofi-Aventis Deutschland Gmbh | Formulacija fiksnog omjera inzulin glargin/liksisenatid |
TWI748945B (zh) | 2015-03-13 | 2021-12-11 | 德商賽諾菲阿凡提斯德意志有限公司 | 第2型糖尿病病患治療 |
TW201705975A (zh) | 2015-03-18 | 2017-02-16 | 賽諾菲阿凡提斯德意志有限公司 | 第2型糖尿病病患之治療 |
WO2018096164A1 (en) * | 2016-11-28 | 2018-05-31 | Novo Nordisk A/S | Insulin degludec for treating diabetes |
EP3544683A1 (en) | 2016-11-28 | 2019-10-02 | Novo Nordisk A/S | Insulin degludec in cardiovascular conditions |
WO2018096163A1 (en) * | 2016-11-28 | 2018-05-31 | Novo Nordisk A/S | Insulin degludec for improvement of glycaemic control and reduction of acute and long-term diabetes complications |
US11366189B2 (en) * | 2020-09-25 | 2022-06-21 | Uih America, Inc. | Systems and methods for magnetic resonance imaging |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001206856A (ja) * | 2000-01-24 | 2001-07-31 | Pfizer Prod Inc | グリコーゲンホスホリラーゼ阻害剤を用いる糖尿病性心筋症の処置方法 |
WO2001080852A1 (en) * | 2000-04-19 | 2001-11-01 | Borody Thomas J | Compositions and therapies for hyperlipidaemia-associated disorders |
WO2002034259A1 (en) * | 2000-10-26 | 2002-05-02 | Fournier Laboratories Ireland Limited | Combination of fenofibrate and coenzyme q10 for the treatment of endothelial dysfunction |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001206856A (ja) * | 2000-01-24 | 2001-07-31 | Pfizer Prod Inc | グリコーゲンホスホリラーゼ阻害剤を用いる糖尿病性心筋症の処置方法 |
WO2001080852A1 (en) * | 2000-04-19 | 2001-11-01 | Borody Thomas J | Compositions and therapies for hyperlipidaemia-associated disorders |
WO2002034259A1 (en) * | 2000-10-26 | 2002-05-02 | Fournier Laboratories Ireland Limited | Combination of fenofibrate and coenzyme q10 for the treatment of endothelial dysfunction |
Non-Patent Citations (4)
Title |
---|
JPN6010013096; Diabetes Care vol.24, no.4, 2001, p.631-636 * |
JPN6010013099; 動脈硬化 第12巻、第5号, 1984, p.1293-1297 * |
JPN6011050508; Diabetes Care vol.25, no.12, 2002, p.2141-2146 |
JPN6011050509; Metabolism, Clinical and Experimental vol.46, Suupl.1, 1997, p.56-60 |
Cited By (3)
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JP2015512908A (ja) * | 2012-03-28 | 2015-04-30 | サノフイ | 基礎インスリン療法 |
JP2019505503A (ja) * | 2015-12-23 | 2019-02-28 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 心臓の代謝性に対するランタスの効果 |
JP7138565B2 (ja) | 2015-12-23 | 2022-09-16 | サノフィ-アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 心臓の代謝性に対するランタスの効果 |
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PT2596800T (pt) | 2016-12-02 |
US20080287343A1 (en) | 2008-11-20 |
DK2596800T3 (en) | 2016-12-12 |
AU2004206829A1 (en) | 2004-08-05 |
IL169697A (en) | 2011-06-30 |
US7405196B2 (en) | 2008-07-29 |
AU2010202738A1 (en) | 2010-07-22 |
MXPA05007470A (es) | 2005-09-21 |
IL169697A0 (en) | 2007-07-04 |
US20130012433A1 (en) | 2013-01-10 |
AU2004206829B2 (en) | 2010-04-08 |
IL197739A (en) | 2017-02-28 |
ES2604359T3 (es) | 2017-03-06 |
SI2596800T1 (sl) | 2017-04-26 |
GB0309154D0 (en) | 2003-05-28 |
WO2004064862A1 (en) | 2004-08-05 |
BRPI0406499A (pt) | 2005-12-06 |
EP2596800A1 (en) | 2013-05-29 |
AU2010202738B2 (en) | 2013-12-05 |
IL208525A0 (en) | 2010-12-30 |
US8809270B2 (en) | 2014-08-19 |
US20110281793A1 (en) | 2011-11-17 |
JP5389325B2 (ja) | 2014-01-15 |
IL197739A0 (en) | 2011-08-01 |
EP1589991A1 (en) | 2005-11-02 |
US20040229774A1 (en) | 2004-11-18 |
EP2596800B1 (en) | 2016-08-24 |
US7977310B2 (en) | 2011-07-12 |
CA2512820A1 (en) | 2004-08-05 |
CY1118738T1 (el) | 2017-07-12 |
HUE031892T2 (en) | 2017-08-28 |
CA2512820C (en) | 2013-06-04 |
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