DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 9,074,015 B2 Lancaster Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 9,074,015 B2 Lancaster Et Al US009074015B2 (12) United States Patent (10) Patent No.: US 9,074,015 B2 Lancaster et al. (45) Date of Patent: Jul. 7, 2015 (54) RECOMBINANTLY EXPRESSED INSULIN 5,922,675 A 7, 1999 Baker et al. POLYPEPTIDES AND USES THEREOF 33. A E. s al. SO (75) Inventors: Thomas M. Lancaster, Stoneham, MA 6,034,054 A 3/2000 DeFelippis et al. (US); Sylaja Murikipudi, Medford, MA 1932 R 38: SE tal (US); Rassol Laleau, Woburn, MA 6,323,3114. r. I B1 1 1/2001 Liujeldsen et al. et al. (US); Todd C. Zion, Marblehead, MA 6,342,225 B1 1/2002 Jones et al. (US) 6.410,053 B1 6/2002 Taylor (73) Assignee: SMARTCELLS, INC., Whitehouse 39SR. 339; its at Station, NJ (US) 6,551992 B1 4/2003 DeFelippis et al. (*) Notice: Subject to any disclaimer, the term of this 6,777.207 B2 8/2004 Kjeldsen et al. patent is extended or adjusted under 35 (Continued) U.S.C. 154(b) by 0 days. FOREIGN PATENT DOCUMENTS (21) Appl. No.: 13/811,910 (22) PCT Filed: Jul. 22, 2011 CN 1O1273961 10, 2008 EP O09842 4f1980 (86). PCT No.: PCT/US2O11AO4SOO8 (Continued) S371 (c)(1), (2), (4) Date: Jan. 24, 2013 OTHER PUBLICATIONS UniProtKB/Swiss-Prot Accession No. PO1314 (accessed Aug. 20, (87) PCT Pub. No.: WO2012/015692 2014 at URL uniprot.org/uniprot/P01314).* PCT Pub. Date: Feb. 2, 2012 UniProtKB/Swiss-Prot Accession No. C9JNR5 (accessed Aug. 20. O O 2014 at URL uniprot.org/uniprot/C9JNR5).* (65) Prior Publication Data UniProtKB/Swiss-Prot Accession No. P30410 (accessed Aug. 20, US 2013/O190476A1 Jul 25, 2013 2014 at URL uniprot.org/uniprot/P30410).* • 1-a-s Zion, Bringing the Cure Home, Slideshare.net, PowerPoint presen tation-2-1319001 (Apr. 6, 2009). Related U.S. Application Data Chu, Smart Insulin, MIT Technology Review, p. 2. (Oct. 30, 2008). (60) Provisional application No. 61/368,607, filed on Jul. Baudys, et al., “Physical Stabilization of Insulin by Glycosylation'J 28, 2010. Pharma Sci (1995) 64:28-33. Brownlee & Cerami, "A Glucose-Controlled-Insulin-Delivery-Sys (51) Skuo (2006.01) tem: Semisynthetic Insulin Bound to Lectin' Diabetes (1983) 32:499-504. A61 K38/28 (2006.01) (Continued) (52) U.S. Cl. CPC C07K 14/62 (2013.01); A6 IK 38/28 (2013.01) (58) Field of Classification Search Primary Examiner — Julie Ha CPC .......... ... SES 66. SS ,% Assistant Examiner — Kristina M Hellman See application file for complete search history (74) Attorney, Agent, or Firm — Immac J. Thampoe; John David Reilly (56) References Cited U.S. PATENT DOCUMENTS (57) ABSTRACT 3.591,574 A 7, 1971 Fenichel et al. The present disclosure provides recombinantly expressed 3,684,791 A 8/1972 Geiger et al. insulin polypeptides that comprise an N-linked glycan motif. 3,847,890 A 11/1974 Green et al. The N-linked glycan motif is not present in wild-type insulins 4,348,387 A 9, 1982 Brownlee et al. and enables the recombinant expression of glycosylated insu 4,372,948 A 2f1983 Yoshikumi et al. lin polypeptides (e.g., in yeast cells). Based on results 4,377.567 A 3, 1983 Geho 4,444,683 A 4, 1984 Kim et al. obtained with synthetic glycosylated insulin conjugates we 4,603,044 A 7, 1986 Geho et al. predict that when these recombinant glycosylated insulin 4,863,896 A 9, 1989 Geho et al. polypeptides are administered to a mammal, at least one 5,239,062 A 8, 1993 Battler et al. pharmacokinetic or pharmacodynamic property of the glyco 5,395,924 A 3, 1995 Battler et al. 5,461,031 A 10/1995 De Felippis Sylated insulin polypeptide will be sensitive to serum concen 5,478,575 A 12/1995 Miyazaki et al. trations of glucose (or an exogenous saccharide Such as alpha 5,527,524. A 6, 1996 Tomalia et al. methyl mannose). Exemplary insulin polypeptides, 5,563,056 A 10, 1996 Swan et al. polynucleotides encoding these insulin polypeptides, glyco 5,723,589 A 3/1998 Miljkovic et al. Sylated insulin polypeptides, pharmaceutical formulations 5,830,506 A 1 1/1998 Taylor 5,843,886 A 12/1998 Weiner et al. and Sustained release formulations are provided in addition to 5,854.208 A 12/1998 Jones et al. methods of use and preparation. 5,866.538 A 2/1999 Norup et al. 5,902,607 A 5/1999 Taylor 5,905,140 A 5, 1999 Hansen 7 Claims, 50 Drawing Sheets US 9,074.015 B2 Page 2 (56) References Cited WO WO2006/082184 8, 2006 WO WO2006/088473 8, 2006 U.S. PATENT DOCUMENTS WO WO2006,102762 10, 2006 WO WO2007/042470 4/2007 6,844,166 Bl 1/2005 Wolf WO WO2007/043050 4/2007 6,869,930 B1 3, 2005 Havelund et al. WO WO2008/O12440 1, 2008 RE39,055 E 4, 2006 Jones et al. WO WO2008/O12528 1, 2008 7,063,863 B2 6, 2006 Taylor WO WO2008/036147 3, 2008 7,087.408 B2 8, 2006 Kjeldsen et al. WO WO2008/065372 6, 2008 7,101,971 B2 9, 2006 Meade et al. WO WO2009/033588 3, 2009 7,105,314 B2 9, 2006 Kjeldsen WO WO2009/05.9450 5, 2009 7,138,371 B2 11/2006 DeFrees et al. WO WO92f1 1378 T 2009 7,316,999 B2 1, 2008 Hoeg-Jensen et al. WO WO2009/089396 T 2009 7,317,000 B2 1, 2008 Hoeg-Jensen et al. WO WO2009/104.199 8, 2009 7,423,014 B2 9, 2008 Ekwuribe et al. WO WO2010.001134 1, 2010 7,531, 191 B2 5/2009 Zion et al. WO WO 2010.001134 A2 * 1, 2010 7,687,608 B2 3, 2010 Lancaster et al. WO WO2O10O882.94 8, 2010 8,062,668 B2 11/2011 Ying et al. WO WO2O11/OOO823 1, 2011 2006, OO19874 A1 1, 2006 Radhakrishnan et al. 2006/0216265 A1 9, 2006 Goodman et al. OTHER PUBLICATIONS 2006, O247154 A1 11, 2006 Palmieri et al. 2007/009982O A1 5/2007 Lancaster et al. Brownlee & Cerami. "Glycosylated Insulin Complexed to 2007/0207498 A1 9, 2007 Palmieri et al. Concanavalin A' Science (1979) 206: 1190-1191. 2009.0053167 A1 2, 2009 DeFrees Dea, et al., “Albumin Binding of Acylated Insulin (NN304) DoesNot 2009/O137454 A1 5/2009 Fynbo et al. Deter Action to Stimulate Glucose Uptake” Diabetes (2002) 51: 2010/0130726 A1 5, 2010 Lancaster et al. T62-769. 2010/0266698 A1 10, 2010 Filvaroffet al. Eggert, et al., “A New Glucose Selective Fluorescent Bisboronic 2010, O298.212 A1 11, 2010 Miao et al. Acid'J Org Chem (1999) 64:3846-3852. 2011/0275560 A1 11/2011 Zion et al. Heinnemann, et al., “Time-action profile of the soluble, fatty acid 2011/0281791 A1 11, 2011 Zion et al. acylated, long acting insulin analogue NN304” Diabetic Med (1999) 2011/0281792 A1 11, 2011 Zion et al. 16:332-338. 2011/0281939 A1 11, 2011 Zion et al. Jeong, et al., “Self Regulating Insulin Delivery Systems I. Synthesis 2011/030 1083 A1 12, 2011 Zion et al. and Characterization of Glycosylated Insulin' J of Controlled 2012, 0046223 A1 2, 2012 Zion et al. Release (1984) 1: 57-66. Lee et al., “Biochemistry of crbohydrate-protein interaction” FASEB FOREIGN PATENT DOCUMENTS J (1992) 3193-3200. Monsigny, et al., “Endogenous Lectins and Drug Targeting” Annals EP O1196.50 9, 1984 NY AcadSci (1988) 551:399-414. EP O725648 8, 1996 Ruziak, et al., “Basal activity profiles of NPH and Ne-palmitoyl Lys RU 2381.238 8, 2009 (B29) human insulins in subjects with IDDM” Diabetologia (1998) WO WO81 00354 2, 1981 41: 116-120. WO WO84/O1896 5, 1984 Shojaee-Moradie, “Novel Hepatoselective Insulin Analog” Diabetes WO WO90, 10645 9, 1990 Care (2000) 23: 1124-1129. WO WO921 1378 A1 * 7, 1992 Yamazaki, et al., “Endogenous lectins as targets for drug delivery WO WO99/52934 10, 1999 Adv. Drug Delivery Rey (2000) 43:225-244. WO WOO1.92334 12/2001 WO WOO3,O18636 3, 2003 Yang et al., Tissue Targeting of Multivalent GalNAc Lex Terminated WO WOO3,O35O11 5, 2003 N-Glycans in Mice, Glycbiology 2000, vol. 10, p. 1341-1345. WO WOO3/047462 6, 2003 Office Action for U.S. Appl. No. 13/145.532 dated Sep. 15, 2014. WO WOO3/0489.15 6, 2003 Response to Office Action for U.S. Appl. No. 13/145.532 dated Dec. WO WOO3,O74087 9, 2003 4, 2014. WO WO2004/057 002 T 2004 WO WO2006/0O8238 1, 2006 * cited by examiner U.S. Patent Jul. 7, 2015 Sheet 1 of 50 US 9,074,015 B2 o GlcNAc: N-Acetylglucosamine NANA: N-Acetylneuraminic Acid OH HO OH HO-20 "S-HO NH OH l?o Os, H0 OH DMon: Monnose (2 Gal: Galactose O Glo: Glucose OH OH HO-a--0 OH HO OH HO s OH HO l OH HO OOH FIG. 1A GlcNAc2Mans GlcNAc2Mang GlcNAc2Man5(GlcNAc2 -- -- GlcNAc)Man5 -: GlcNAc2Man5(GlcNAc20al -- GlcNAC2 Mong-100 GlcNAc)Man5 -- . GlcNAc2Man5(GlcNAc20al?NANA2 GlcNAc2Mon3 ". GlcNAc2Man5(GlcNAc GlcNAc2Mang Glc3 --- -- GlcNAc2Man5(GlcNAc -- -- FIG. 1B U.S. Patent Jul. 7, 2015 Sheet 3 Of 50 US 9,074,015 B2 Endoplasmic Reticulum Golgi GlcNAc2MangGlc3 GlcNAc)Mang -- O-E. Glucosidose J. 1,6-MnT Glucosidase I GlcNAc2Mang GlcNAc2Mang N -- Series of 1,6-MnT and Transport to GlcNAC2 Mong-100 1,2-MnT Golgi 6. in S. cerevisiae, not in P. pastoris FIG.3 U.S. Patent Jul. 7, 2015 Sheet 4 of 50 US 9,074,015 B2 A0ch 1p Gene Endoplasmic Reticulum GlcNAc2MangGlc3 Glucosidose Glucosidase I GlcNAc2ManB GlcNAc2Man5 P. pastoris does not have an a-1,3-MnS FIG.4A U.S.
Load more

Recommended publications
  • Evidenz Und Versorgungsrealität Von Kurzwirksamen Insulinanaloga in Der Behandlung Des Typ-2-Diabetes Mellitus
    Evidenz und Versorgungsrealität von kurzwirksamen Insulinanaloga in der Behandlung des Typ-2-Diabetes mellitus – Eine Versorgungsanalyse auf der Basis von Sekundärdaten – Dissertation zur Erlangung des Doktorgrades der Naturwissenschaften vorgelegt beim Fachbereich 14 - Biochemie, Chemie und Pharmazie der Johann Wolfgang Goethe-Universität in Frankfurt am Main von Matthias S. Pfannkuche aus Brühl Frankfurt am Main, im Jahr 2009 vom Fachbereich 14 - Biochemie, Chemie und Pharmazie der Johann Wolfgang Goethe-Universität als Dissertation angenommen. Dekan: Prof. Dr. rer. nat. Dieter Steinhilber Gutachter: Prof. Dr. rer. nat. Theo Dingermann Prof. Dr. rer. nat. Gerd Glaeske (Universität Bremen) Datum der Disputation: 15. Februar 2010 Bildnachweis Titelseite: Insulin Hexamer: http://commons.wikimedia.org/wiki/File:Human-insulin-hexamer-3D-ribbons.png (letzter Zugriff: 11.06.2009) Non semper ea sunt, quae videntur. (Phädrus, fabulae 4, 2, 5) Danksagung Diese Dissertation sowie die hiermit in Verbindung stehenden Publikationen wären ohne die Anregungen und Unterstützung durch viele Kollegen, Freunde und Organisationen nicht möglich gewesen. Ihnen möchte ich an dieser Stelle danken. Mein besonderer Dank gilt Prof. Dr. rer. nat Gerd Glaeske und Prof. Dr. rer. nat. Theo Dingermann, die diese Arbeit in vielerlei Hinsicht erst ermöglichten. Überaus dankbar bin ich Prof. Dr. rer. nat. Gerd Glaeske für die freundliche Aufnahme in seine Arbeitsgruppe, die es mir ermöglichte weitere Einblicke in die Gesundheitsökonomie, Gesundheitspolitik und Versorgungsforschung zu nehmen. Für das Korrekturlesen der kompletten Arbeit, die zahlreichen Hinweise und konstruktiven Diskussionen sowie die zahlreichen Mittagspausen danke ich im besonderen Dr. P.H. Falk Hoffmann. Herzlicher Dank gilt auch dem gesamten Arbeitskreis in Bremen sowie den Projektbeteiligten Krankenkassen, allen voran der GEK, die mir durch den Zugriff auf ihre Daten erst viele Analysen ermöglichten.
    [Show full text]
  • LANTUS® (Insulin Glargine [Rdna Origin] Injection)
    Rev. March 2007 Rx Only LANTUS® (insulin glargine [rDNA origin] injection) LANTUS® must NOT be diluted or mixed with any other insulin or solution. DESCRIPTION LANTUS® (insulin glargine [rDNA origin] injection) is a sterile solution of insulin glargine for use as an injection. Insulin glargine is a recombinant human insulin analog that is a long-acting (up to 24-hour duration of action), parenteral blood-glucose-lowering agent. (See CLINICAL PHARMACOLOGY). LANTUS is produced by recombinant DNA technology utilizing a non- pathogenic laboratory strain of Escherichia coli (K12) as the production organism. Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain. Chemically, it is 21A- B B Gly-30 a-L-Arg-30 b-L-Arg-human insulin and has the empirical formula C267H404N72O78S6 and a molecular weight of 6063. It has the following structural formula: LANTUS consists of insulin glargine dissolved in a clear aqueous fluid. Each milliliter of LANTUS (insulin glargine injection) contains 100 IU (3.6378 mg) insulin glargine. Inactive ingredients for the 10 mL vial are 30 mcg zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, 20 mcg polysorbate 20, and water for injection. Inactive ingredients for the 3 mL cartridge are 30 mcg zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, and water for injection. The pH is adjusted by addition of aqueous solutions of hydrochloric acid and sodium hydroxide. LANTUS has a pH of approximately 4. CLINICAL PHARMACOLOGY Mechanism of Action: The primary activity of insulin, including insulin glargine, is regulation of glucose metabolism.
    [Show full text]
  • Diabetes Mellitus: Patterns of Pharmaceutical Use in Manitoba
    Diabetes Mellitus: Patterns of Pharmaceutical Use in Manitoba by Kim¡ T. G. Guilbert A Thesis submitted to The Faculty of Graduate Studies in Partial Fulfillment of the Requirements for the Degree of MASTER OF SCIENCE Faculty of Pharmacy The University of Manitoba Winnipeg, Manitoba @ Kimi T.G. Guilbert, March 2005 TIIE UMYERSITY OF MANITOBA F'ACULTY OF GRADUATE STTJDIES +g+ù+ COPYRIGIIT PERMISSION PAGE Diabetes Mellitus: Patterns of Pharmaceutical Use in Manitoba BY Kimi T.G. Guilbert A ThesisÆracticum submitted to the Faculty of Graduate Studies of The University of Manitoba in partial fulfillment of the requirements of the degree of MASTER OF SCIENCE KIMI T.G. GTIILBERT O2()O5 Permission has been granted to the Library of The University of Manitoba to lend or sell copies of this thesis/practicum, to the National Library of Canada to microfïlm this thesis and to lend or sell copies of the film, and to University Microfilm Inc. to publish an abstract of this thesis/practicum. The author reserves other publication rights, and neither this thesis/practicum nor extensive extracts from it may be printed or otherwise reproduced without the author's written permission. Acknowledgements Upon initiation of this project I had a clear objective in mind--to learn more. As with many endeavors in life that are worthwhile, the path I have followed has brought me many places I did not anticipate at the beginning of my journey. ln reaching the end, it is without a doubt that I did learn more, and the knowledge I have been able to take with me includes a wider spectrum than the topic of population health and medication utilization.
    [Show full text]
  • A Critical Appraisal of the Role of Insulin Analogues in the Management of Diabetes Mellitus Ralph Oiknine, Marla Bernbaum and Arshag D
    Drugs 2005; 65 (3): 325-340 REVIEW ARTICLE 0012-6667/05/0003-0325/$39.95/0 2005 Adis Data Information BV. All rights reserved. A Critical Appraisal of the Role of Insulin Analogues in the Management of Diabetes Mellitus Ralph Oiknine, Marla Bernbaum and Arshag D. Mooradian Division of Endocrinology, Department of Internal Medicine, Diabetes, and Metabolism, St Louis University School of Medicine, St Louis, Missouri, USA Contents Abstract ....................................................................................325 1. Physiology of Insulin Secretion .............................................................326 2. Conventional Insulin Preparations ..........................................................327 3. Insulin Analogues ........................................................................328 3.1 Rapid-Acting Insulin Analogues .......................................................328 3.1.1 Insulin Lispro ...................................................................328 3.1.2 Insulin Aspart ..................................................................329 3.1.3 Insulin Glulisine .................................................................329 3.1.4 Clinical Utility of Rapid-Acting Insulin Analogues ...................................330 3.2 Premixed Insulins and Insulin Analogues ................................................331 3.3 Basal Insulin Analogues ...............................................................331 3.3.1 Insulin Glargine ................................................................331
    [Show full text]
  • IHS PROVIDER September 2017
    September 2017 Volume 42 Number 9 Indian Health Service National Pharmacy and Therapeutics Committee SGLT-2 inhibitors (Update) NPTC Formulary Brief August Meeting 2017 Background: The FDA has currently approved three SGLT-2 inhibitors, two of which have completed FDA-mandated cardiovascular outcomes trials. Last year, in the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG), empagliflozin not only reduced cardiovascular events, but also mortality.1 This year, the Canagliflozin Cardiovascular Assessment Study (CANVAS) demonstrated equivocal cardiovascular benefits, no mortality benefit, and significant harms in those receiving canagliflozin.2 The DECLARE-TIMI 58 cardiovascular study of dapagliflozin will be completed in April 2019 (ClinicalTrials.gov Identifier: NCT01730534). Uncertainty remains regarding the current data, long- term benefits and harms, and differentiation among SGLT-2 inhibitors. Following a review of SGLT2 inhibitors at the August 2017 NPTC meeting on their cardiovascular outcomes, net benefit and place in therapy, no modifications were made to the National Core Formulary (NCF). Discussion: EMPA-REG enrolled 7,020 patients with Type 2 diabetes mellitus (T2DM) and HgbA1c values between 7.0-10.0%. All patients had established cardiovascular disease (CVD) and were observed for a median duration of 3.1 years. Empagliflozin reduced the primary outcome of cardiovascular (CV) death, nonfatal myocardial infarction (MI), or nonfatal cardiovascular accident (CVA) by 6.5 events per 1000 patient-years (pt-yrs). Mortality decreased by 9.2 events per 1000 pt-yrs, primarily driven by a reduction in CV mortality of 7.8 events per 1000 pt-yrs. Heart failure hospitalization decreased by 5.1 events per 1000 pt-yrs.
    [Show full text]
  • Type 2 Diabetes Adult Outpatient Insulin Guidelines
    Diabetes Coalition of California TYPE 2 DIABETES ADULT OUTPATIENT INSULIN GUIDELINES GENERAL RECOMMENDATIONS Start insulin if A1C and glucose levels are above goal despite optimal use of other diabetes 6,7,8 medications. (Consider insulin as initial therapy if A1C very high, such as > 10.0%) 6,7,8 Start with BASAL INSULIN for most patients 1,6 Consider the following goals ADA A1C Goals: A1C < 7.0 for most patients A1C > 7.0 (consider 7.0-7.9) for higher risk patients 1. History of severe hypoglycemia 2. Multiple co-morbid conditions 3. Long standing diabetes 4. Limited life expectancy 5. Advanced complications or 6. Difficult to control despite use of insulin ADA Glucose Goals*: Fasting and premeal glucose < 130 Peak post-meal glucose (1-2 hours after meal) < 180 Difference between premeal and post-meal glucose < 50 *for higher risk patients individualize glucose goals in order to avoid hypoglycemia BASAL INSULIN Intermediate-acting: NPH Note: NPH insulin has elevated risk of hypoglycemia so use with extra caution6,8,15,17,25,32 Long-acting: Glargine (Lantus®) Detemir (Levemir®) 6,7,8 Basal insulin is best starting insulin choice for most patients (if fasting glucose above goal). 6,7 8 Start one of the intermediate-acting or long-acting insulins listed above. Start insulin at night. When starting basal insulin: Continue secretagogues. Continue metformin. 7,8,20,29 Note: if NPH causes nocturnal hypoglycemia, consider switching NPH to long-acting insulin. 17,25,32 STARTING DOSE: Start dose: 10 units6,7,8,11,12,13,14,16,19,20,21,22,25 Consider using a lower starting dose (such as 0.1 units/kg/day32) especially if 17,19 patient is thin or has a fasting glucose only minimally above goal.
    [Show full text]
  • Effects of Basal Insulin Analog and Metformin on Glycaemia Control and Weight As Risk &Factors for Endothelial Dysfunction
    EFFECTS OF BASAL INSULIN ANALOG AND METFORMIN ON GLYCAEMIA CONTROL AND WEIGHT AS RISK &FACTORS FOR ENDOTHELIAL DYSFUNCTION Belma Aščić – Buturović¹*, Mirsad Kacila² ¹ Clinic of Endocrinology, Diabetes Mellitus and Metabolic Diseases, University of Sarajevo Clinics Centre, Bolnička , Sarajevo, Bosnia and Herzegovina ² Center for Heart Diseases, University of Sarajevo Clinics Centre, Bolnička , Sarajevo, Bosnia and Herzegovina * Corresponding author Abstract Obese patients with type diabetes and impaired glucose tolerance are at increased risk of develop- ment of cardiovascular diseases. Endothelial dysfunction may be a reason for development of ath- erosclerosis and cardiovascular diseases. Lifestyle modifi cation, increased physical activity, weight reduction, energy restricted diet and good glycaemia control can be useful for the endothelial func- tion improvement and may decrease the risk of cardiovascular diseases. Th e aim of this study was to evaluate the eff ects of basal insulin analog and metformin on glycaemia control and weight as risk factors of endothelial dysfunction. Total of patients ( male and female) with type dia- betes were studied. Th e patients were monitored over six months period. Glycated hemoglobin (HbAc), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and body mass index (BMI) were observed. Mean age of the subjects was , ± , years. Mean diabetes duration was , ± , years. At the end of the study mean body mass index decreased from , ± , kg/m to , ±, kg/m. In this study we included diabetic patients with fasting glycaemia over mmol/ dm, postmeal glycaemia over , mmol/dm and glycated hemoglobin over . Prior to the study, the patients were treated with premix insulin divided in two daily doses and metformin after the lunch, which did not result in suffi cient regulation of glycaemia.
    [Show full text]
  • Tresiba-Product-Monograph.Pdf
    PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION TRESIBA® insulin degludec injection TRESIBA® FlexTouch® 100 U/mL, Solution for injection in a pre-filled pen TRESIBA® FlexTouch® 200 U/mL, Solution for injection in a pre-filled pen Subcutaneous Antidiabetic Agent Long-Acting Basal Insulin Analogue ATC Code: A10AE06 Novo Nordisk Canada Inc. Date of Initial Authorization: AUG 25, 2017 101-2476 Argentia Road Date of Revision: Mississauga, Ontario JUL 23, 2021 Canada L5N 6M1 Submission Control Number: 250276 Product Monograph Master Template Template Date: September 2020 TRESIBA® (insulin degludec injection) Page 1 of 2 RECENT MAJOR LABEL CHANGES 7 Warnings and Precautions 03/2021 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. TABLE OF CONTENTS ..............................................................................................................2 1 INDICATIONS ..................................................................................................................4 1.1 Pediatrics ................................................................................................................4 1.2 Geriatrics ................................................................................................................4 2 CONTRAINDICATIONS ..................................................................................................4 3 SERIOUS WARNINGS AND PRECAUTIONS BOX .......................................................4 4 DOSAGE AND ADMINISTRATION
    [Show full text]
  • INSULIN-CONTAINING PRODUCTS from NOVO NORDISK Storage, and Savings Information
    Please see the following pages for Tresiba®, ® ® Xultophy 100/3.6, and Fiasp Dosing, 1 INSULIN-CONTAINING PRODUCTS FROM NOVO NORDISK Storage, and Savings Information. BASAL 100 units/mL; total of 200 units/mL; total of 100 units/mL; total of 300 units/pen; 5-pen pack1 600 units/pen; 3-pen pack1 1000 units/vial; 1 vial/pack1 NDC: 0169-2660-15 NDC: 0169-2550-13 NDC: 0169-2662-11 100 units/mL insulin degludec and 3.6 mg/mL liraglutide; total of 300 units insulin degludec and 10.8 mg liraglutide; 5-pen pack2 NDC: 0169-2911-15 BASAL/GLP-1 RA Approved for use in pumps3 Refer to the insulin infusion pump user manual to see if Fiasp® can be used. Use in accordance with the insulin pump’s Instructions for Use. 100 units/mL; total of 300 units; 100 units/mL; total of 100 units/mL; total of PRANDIAL 5-pen pack3 300 units/pen; 5-cartridge pack3 1000 units/vial; 1 vial/pack3 NDC: 0169-3204-15 NDC: 0169-3205-15 NDC: 0169-3201-11 GLP-1 RA=glucagon-like peptide-1 receptor agonist. Tresiba® Indications and Usage Xultophy® 100/3.6 Indications and Xultophy® 100/3.6 Important Safety Fiasp® Indications and Usage Tresiba® (insulin degludec injection) is indicated to Limitations of Use Information Fiasp® (insulin aspart injection) 100 U/mL is a improve glycemic control in patients 1 year of age and Xultophy® 100/3.6 (insulin degludec and liraglutide injection) rapid-acting insulin analog indicated to improve older with diabetes mellitus. WARNING: RISK OF THYROID C-CELL TUMORS 100 units/mL and 3.6 mg/mL is a combination of insulin ® glycemic control in adult and pediatric patients with degludec and liraglutide and is indicated as an adjunct to diet • Liraglutide, one of the components of Xultophy 100/3.6, causes dose-dependent and treatment-duration-dependent thyroid diabetes mellitus.
    [Show full text]
  • 8. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2018
    Diabetes Care Volume 41, Supplement 1, January 2018 S73 8. Pharmacologic Approaches to American Diabetes Association Glycemic Treatment: Standards of Medical Care in Diabetesd2018 Diabetes Care 2018;41(Suppl. 1):S73–S85 | https://doi.org/10.2337/dc18-S008 8. PHARMACOLOGIC APPROACHES TO GLYCEMIC TREATMENT The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations, please refer to the Standards of Care Introduction. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. PHARMACOLOGIC THERAPY FOR TYPE 1 DIABETES Recommendations c Most people with type 1 diabetes should be treated with multiple daily in- jections of prandial insulin and basal insulin or continuous subcutaneous insulin infusion. A c Most individuals with type 1 diabetes should use rapid-acting insulin analogs to reduce hypoglycemia risk. A c Consider educating individuals with type 1 diabetes on matching prandial insulin doses to carbohydrate intake, premeal blood glucose levels, and anticipated physical activity. E c Individuals with type 1 diabetes who have been successfully using continuous subcutaneous insulin infusion should have continued access to this therapy after they turn 65 years of age.
    [Show full text]
  • Dynamic Approaches to Improve Glycemic Control and Primary Diabetes Care 1‑Or 2‑Or 3‑Or
    DYNAMIC APPROACHES TO IMPROVE GLYCEMIC CONTROL AND PRIMARY DIABETES CARE DYNAMIC APPROACHES TO IMPROVE GLYCEMIC Figure. CONTROL AND PRIMARY DIABETES CARE 1‑OR Characterizing Clinical Inertia in a Large, National Database CORI R. RATTELMAN, ANUPAMA ARORA, JOHN K. CUDDEBACK, ELIZABETH L. CIEMINS, Alexandria, VA Objective: To characterize clinical inertia in the treatment of diabetes using a large, geographically diverse clinical database. Study Design: A retrospective descriptive analysis was conducted in a clinical database containing 22 million patient records across 22 health care organizations (HCOs). Population Studied: A total of 281,000 patients aged 18-75 were included during the 5.5-year study period (1/2012-6/2017). Patients had an outpatient visit in the last 12 months of the study period, an HbA1c in the last 24-30 months (index A1c), and a diagnosis of type 2 DM on a claim or EHR prob- lem list at least 6 months prior to index A1c. A subset of 47,693 patients with an index A1c ≥8 and a prior A1c ≥8 or lack thereof, was observed for Supported By: National Institute of Diabetes and Digestive and Kidney Diseases four 6-month follow-up periods for actions including a new class of diabetes (T35DK104689); Yale University medication prescribed or an A1c <8. The absence of observable action fol- lowing index A1c suggests potential “clinical inertia.” Principal Findings: Six months following an index A1c≥8, 55% of patients 3‑OR received no observable clinical action ranging from 45-65% across HCOs Influence of Diabetes Complications on the Cost‑Effectiveness of and 18-96% across individual providers.
    [Show full text]
  • Diabetes: Putting It All Together to Design a High Value Diabetes Regimen for Your Patient
    Diabetes: Putting it all together to design a high value diabetes regimen for your patient Cecilia C. Low Wang, MD Professor of Medicine Division of Endocrinology, Metabolism and Diabetes University of Colorado School of Medicine [email protected] Disclosures • None Objectives • Describe the benefits, side effects/risks, and costs of the newer diabetes medications • Discuss the value of the newer diabetes medications • Make high-value patient-centered decisions when intensifying diabetes therapy Worsening HbA1c • Ms L is a 48 year old woman here for routine f/u • She has Type 2 diabetes (x 5 years; no complications), obesity (BMI 41), chronic knee pain from osteoarthritis, and is postmenopausal s/p TAH 6 yr ago for uterine leiomyomas • You last saw her 6 months ago. At that time, her A1c was 6.4% on metformin 1000 mg BID • You see that her A1c is now 8.5%. • What other information do you need? • How would you intensify her diabetes treatment? “New-onset” diabetes • Mr. B is a 53 year old M hospitalized for NSTEMI and underwent 3v CABG • He had HTN but no other medical history and was on no medications prior to admission • Admission point-of-care (POC) glucose: 263 mg/dL • HbA1c: 11.5% • He agrees that he needs to be on insulin upon discharge • Are there any non-insulin medications that should be considered for him? • How would you design his regimen? ADVANCE: Diabetes complications and A1c relationship CVA CV death • Linear relationship (no threshold) for eye complications • J-curve: Increasing DKD Retinopathy risk with A1c <6.5% for CV and renal complications 6 Zoungas, et al.
    [Show full text]