Type 2 Diabetes Adult Outpatient Insulin Guidelines
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Metformin Plus Saxagliptin for Type 2 Diabetes
Treatment evaluation Metformin plus saxagliptin for type 2 diabetes André J. Scheen Division of Diabetes, Nutrition and Metabolic Disorders and Division of Clinical Pharmacology, Department of Medicine, CHU Sart Tilman, University of Liège, Liège, Belgium Running title : Saxagliptin plus metformin Word count : Abstract : 148 Main text : 2404 Tables : 4 Figures : 0 Address for correspondence : Pr André J. SCHEEN Department of Medicine CHU Sart Tilman (B35) B-4000 LIEGE 1 BELGIUM Phone : 32-4-3667238 FAX : 32-4-3667068 Page 1 Email : andre.scheen @ chu.ulg.ac.be SUMMARY Metformin is considered as the first-line drug therapy for the management of type 2 diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors, by promoting insulin secretion and reducing glucagon secretion in a glucose-dependent manner, offer new opportunities for oral therapy after failure of metformin. Saxagliptin, a DPP-4 inhibitor, and metformin may be administered together, separately or in fixed-dose combination (FDC), either as saxagliptin added to metformin or as initial combination in drug-naive patients. Both compounds exert complementary pharmacodynamic actions leading to better improvement in blood glucose control (fasting plasma glucose, postprandial glucose, HbA1c) than either compound separately. Adding saxagliptin to metformin monthotherapy results in a consistent, sustained and safe reduction in HbA1c levels. Tolerance is excellent without hypoglycemia or weight gain. The combination saxaglitpin plus metformin may be used as first-line or second-line therapy in the management of type 2 diabetes, especially as a valuable alternative to the classical metformin-sulfonylurea combination. Key-words : DPP-4 inhibitor – Fixed-dose combination - Metformin – Saxagliptin - Type 2 diabetes mellitus Page 2 1. -
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. -
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. -
CD26/DPP-4: Type 2 Diabetes Drug Target with Potential Influence On
cancers Review CD26/DPP-4: Type 2 Diabetes Drug Target with Potential Influence on Cancer Biology Emi Kawakita 1 , Daisuke Koya 2,3 and Keizo Kanasaki 1,3,* 1 Internal Medicine 1, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan; [email protected] 2 Department of Diabetology & Endocrinology, Kanazawa Medical University, Uchinada 920-0293, Japan; [email protected] 3 Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada 920-0293, Japan * Correspondence: [email protected]; Tel.: +81-853-20-2183 Simple Summary: Dipeptidyl peptidase (DPP)-4 inhibitor is widely used for type 2 diabetes. Al- though DPP-4/CD26 has been recognized as both a suppressor and inducer in tumor biology due to its various functions, how DPP-4 inhibitor affects cancer progression in diabetic patients is still unknown. The aim of this review is to summarize one unfavorable aspect of DPP-4 inhibitor in cancer-bearing diabetic patients. Abstract: DPP-4/CD26, a membrane-bound glycoprotein, is ubiquitously expressed and has diverse biological functions. Because of its enzymatic action, such as the degradation of incretin hormones, DPP-4/CD26 is recognized as the significant therapeutic target for type 2 diabetes (T2DM); DPP- 4 inhibitors have been used as an anti-diabetic agent for a decade. The safety profile of DPP-4 inhibitors for a cardiovascular event in T2DM patients has been widely analyzed; however, a clear association between DPP-4 inhibitors and tumor biology is not yet established. Previous preclinical Citation: Kawakita, E.; Koya, D.; Kanasaki, K. -
Insulin Aspart Sanofi, If It Is Coloured Or It Has Solid Pieces in It
ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions. 1. NAME OF THE MEDICINAL PRODUCT Insulin aspart Sanofi 100 units/ml solution for injection in vial Insulin aspart Sanofi 100 units/ml solution for injection in cartridge Insulin aspart Sanofi 100 units/ml solution for injection in pre-filled pen 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One ml solution contains 100 units insulin aspart* (equivalent to 3.5 mg). Insulin aspart Sanofi 100 units/ml solution for injection in vial Each vial contains 10 ml equivalent to 1,000 units insulin aspart. Insulin aspart Sanofi 100 units/ml solution for injection in cartridge Each cartridge contains 3 ml equivalent to 300 units insulin aspart. Insulin aspart Sanofi 100 units/ml solution for injection in pre-filled pen Each pre-filled pen contains 3 ml equivalent to 300 units insulin aspart. Each pre-filled pen delivers 1-80 units in steps of 1 unit. *produced in Escherichia coli by recombinant DNA technology. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Solution for injection (injection). Clear, colourless, aqueous solution. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Insulin aspart Sanofi is indicated for the treatment of diabetes mellitus in adults, adolescents and children aged 1 year and above. 4.2 Posology and method of administration Posology The potency of insulin analogues, including insulin aspart, is expressed in units, whereas the potency of human insulin is expressed in international units. -
Combining a Glucagon-Like Peptide-1 Receptor Agonist with Basal Insulin: the Why and How
Combining a Glucagon-like Peptide-1 Receptor Agonist with Basal Insulin: The Why and How Case Study Mary is a 61 year-old female diagnosed with type 2 diabetes mellitus (T2DM) 8 years ago. She was initially managed with the combination of lifestyle modification and metformin. Since that time she was treated with a sulfonylurea, but it was discontinued due to symptomatic hypoglycemia. She was also treated with pioglitazone, but significant fluid retention led to it discontinuation. A year-and-a- half ago, basal insulin was added to her lifestyle and metformin management. She now administers 52 units (0.62 units/kg) once daily at bedtime. Since starting basal insulin, she has experienced 3 episodes of mild hypoglycemia. Since her diagnosis, Mary’s HbA1c has never been <7.0%; her current HbA1c is 7.9%. Over the past month, her fasting plasma glucose (FPG) has ranged from 103 mg/dL to 136 mg/dL and her postprandial glucose (PPG) from 164 mg/dL to 213 mg/dL. She has gained 2.6 kg since starting basal insulin and her body mass index is now 31 kg/m2. Her blood pressure is 134/82 mmHg. She experiences occasional tingling in her feet. Eye examination reveals grade 1 retinopathy. Current medications are: metformin 1000mg twice daily, basal insulin 52 units once daily at bedtime, and hydrochlorothiazide 25 mg once daily. Her family physician notes that Mary’s FPG is reasonably well-controlled, yet her HbA1c and PPG remain elevated. He is also concerned about her episodes of hypoglycemia and weight gain and the evidence indicating microvascular damage. -
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. -
Drug Information Center Highlights of FDA Activities
Drug Information Center Highlights of FDA Activities – 3/1/21 – 3/31/21 FDA Drug Safety Communications & Drug Information Updates: Ivermectin Should Not Be Used to Treat or Prevent COVID‐19: MedWatch Update 3/5/21 The FDA advised consumers against the use of ivermectin for the treatment or prevention of COVID‐19 following reports of patients requiring medical support and hospitalization after self‐medicating. Ivermectin has not been approved for this use and is not an anti‐viral drug. Health professionals are encouraged to report adverse events associated with ivermectin to MedWatch. COVID‐19 EUA FAERS Public Dashboard 3/15/21 The FDA launched an update to the FDA Adverse Event Reporting System (FAERS) Public Dashboard that provides weekly updates of adverse event reports submitted to FAERS for drugs and therapeutic biologics used under an Emergency Use Authorization (EUA) during the COVID‐19 public health emergency. Monoclonal Antibody Products for COVID‐19 – Fact Sheets Updated to Address Variants 3/18/21 The FDA authorized revised fact sheets for health care providers to include susceptibility of SARS‐CoV‐2 variants to each of the monoclonal antibody products available through EUA for the treatment of COVID‐19 (bamlanivimab, bamlanivimab and etesevimab, and casirivimab and imdevimab). Abuse and Misuse of the Nasal Decongestant Propylhexedrine Causes Serious Harm 3/25/21 The FDA warned that abuse and misuse of the nasal decongestant propylhexedrine, sold OTC in nasal decongestant inhalers, has been increasingly associated with cardiovascular and mental health problems. The FDA has recommended product design changes to support safe use, such as modifications to preclude tampering and limits on the content within the device. -
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 -
Performance of the Insulin-Only Ilet Bionic Pancreas and The
e118 Diabetes Care Volume 44, June 2021 Performance of the Insulin-Only Luz E. Castellanos,1 Courtney A. Balliro,1 Jordan S. Sherwood,1 Rabab Jafri,1 iLet Bionic Pancreas and the Mallory A. Hillard,1 Evelyn Greaux,1 Rajendranath Selagamsetty,2 Hui Zheng,3 Bihormonal iLet Using Firas H. El-Khatib,2 Edward R. Damiano,2,4 and Dasiglucagon in Adults With Type Steven J. Russell1 1 Diabetes in a Home-Use Setting Diabetes Care 2021;44:e118–e120 | https://doi.org/10.2337/dc20-1086 Reductions in blood glucose levels in with insulin lispro (Eli Lilly) or aspart (Table 1). The mean CGM glucose and people with diabetes are often achieved (Novo Nordisk), the bihormonal iLet for time in range (70–180 mg/dL) were 149 at the expense of increased hypoglyce- 7dayswithdasiglucagon(4mg/mL) ±13mg/dLand72±8%,respectively,in mia. A novel approach is to automati- and insulin lispro or aspart, or both, us- the insulin-only period, and 139 ± 11 cally deliver microdose glucagon when ing the same glucose target (110 mg/ mg/dL and 79 ± 9%, respectively, in the automation of insulin delivery alone is dL), in random order. There were no re- bihormonal period. The mean daily car- not sufficient to prevent hypoglycemia. strictions on diet or exercise. The prima- bohydrates consumed to prevent or The approach requires a bihormonal de- ry outcomes were prespecified iLet treat hypoglycemia were 16 ± 13 g and vice and a stable form of glucagon or operational thresholds. The key second- 18 ± 21 g in the insulin-only and bihor- glucagon analog. -
(Pram) and Insulin A21G Improves Post-Prandial Glucose Vs Novolog
ADO09, A Co-Formulation Of Pramlintide (Pram) and Insulin A21G improves Post-Prandial Glucose Vs Novolog® in Type 1 Diabetes (T1DM) G.Meiffren¹, G.Andersen², R.Eloy¹, C.Seroussi¹, C.Mégret¹, S.Famulla², Y.-P Chan¹, M.Gaudier¹, O.Soula¹, J.H. DeVries²,T.Heise² (1 Adocia, Lyon, France ; 2 Profil, Neuss, Germany) Introduction & Background Overall safety Outpatient period results - CGM metrics o ADO09 (M1Pram) is a co-formulation of pramlintide and insulin A21G o Both treatments were well tolerated without any treatment-related serious adverse events o Most of the CGM metrics (TiR [70-180], TiR [80-140], mean blood glucose per day), were significantly improved developed to leverage the beneficial effects of pramlintide on post-prandial (Table 2). As expected M1Pram had numerically more, mostly gastrointestinal adverse events with M1Pram (Table 4). Postprandial and mean 24-hour glucose profiles were improved with M1Pram (Fig. 3) glucose without additional injections than insulin aspart Table 4: CGM metrics, all days. Significant differences are marked in bold Objective and design o No severe hypoglycemia were seen, slightly more hypoglycemic events occurred with M1Pram Ratio of LSMean* o To compare the effect of M1Pram and insulin aspart (Novolog®, Novo than with aspart (Table 3) Difference Parameter Treatment LS Mean M1Pram / Aspart P-value Nordisk) on post-prandial glucose control, glycemic control assessed by Table 2: Incidence of adverse events throughout the trial (M1Pram-Aspart) (95% CI) CGM and safety/tolerability M1Pram Aspart M1Pram -
Komboglyze, INN-Saxagliptin, Metformin
ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT Komboglyze 2.5 mg/850 mg film-coated tablets Komboglyze 2.5 mg/1,000 mg film-coated tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Komboglyze 2.5 mg/850 mg film-coated tablets Each tablet contains 2.5 mg of saxagliptin (as hydrochloride) and 850 mg of metformin hydrochloride. Komboglyze 2.5 mg/1,000 mg film-coated tablets Each tablet contains 2.5 mg of saxagliptin (as hydrochloride) and 1,000 mg of metformin hydrochloride. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablet (tablet). Komboglyze 2.5 mg/850 mg film-coated tablets Light brown to brown, biconvex, round, film-coated tablets, with “2.5/850” printed on one side and “4246” printed on the other side, in blue ink. Komboglyze 2.5 mg/1,000 mg film-coated tablets Pale yellow to light yellow, biconvex, oval shaped, film-coated tablets, with “2.5/1000” printed on one side and “4247” printed on the other side, in blue ink. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Komboglyze is indicated in adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control: in patients inadequately controlled on their maximally tolerated dose of metformin alone in combination with other medicinal products for the treatment of diabetes, including insulin, in patients inadequately controlled with metformin and these medicinal products (see sections 4.4, 4.5 and 5.1 for available data on different combinations) in patients already being treated with the combination of saxagliptin and metformin as separate tablets.