DOCSLIB.ORG

Risk of Any Hypoglycemia with New Antihyperglycemic Agents in Patients with Type 2 Diabetes: a Systematic Review and Meta-Analysis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Risk of Any Hypoglycemia with New Antihyperglycemic Agents in Patients with Type 2 Diabetes: a Systematic Review and Meta-Analysis Risk of Any Hypoglycemia with New Antihyperglycemic Agents in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis by Sanaz Kamalinia A thesis submitted in conformity with the requirements for the degree of Master of Science Institute of Medical Sciences University of Toronto © Copyright by Sanaz Kamalinia (2019) Risk of Any Hypoglycemia with New Antihyperglycemic Agents in Patients with Type 2 Diabetes: A Systematic Review and Meta- Analysis Sanaz Kamalinia Master of Science Institute of Medical Sciences University of Toronto 2019 Abstract Background : Evaluation of hypoglycemia risk relative to placebo with new antihyperglycemic agents (AHA) including the dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose co-transporter- 2 inhibitors (SGLT2i) remains inconclusive. Objective: This systematic review and meta-analysis aimed to assess risk of any and severe hypoglycemia with new AHA relative to placebo by excluding studies with background sulfonylureas and insulin. Methods: Randomized, placebo-controlled studies, 12 weeks or greater in duration were considered for inclusion. Studies allowing background use of any other AHA, apart from metformin, were excluded. This study is registered with PROSPERO (CRD42018095458). Results: 141 studies included in the meta-analysis demonstrate that relative to placebo, risk of any and severe hypoglycemia did not significantly differ for any new AHA. ii Acknowledgments First and foremost, I wish to express my sincere gratitude to my program advisor committee members. To my supervisor Dr Tobe, thank you for accepting me as your student and presenting me with this challenge. I thoroughly enjoyed it. Especially given your positive words of encouragement and insightful guidance for every step of this journey. To my program advisory committee members, Drs Robert Josse and Baiju Shah, I am so grateful for the collaboration. As icons in your field, thank you for instilling your trust in me. A special note of appreciation to my independent reviewers Lindsay Leduc and Patrick J. Donio for taking on this massive project while in medical school. Their dedication and commitment to detail were key to the success of this analysis. It is reassuring to know the next generation of physicians will be of such high caliber. Finally, to my family. My husband and best friend Fardin, thank you for never questioning and encouraging my mid-life decision to quit my job and return to school. To my precious children, son Kayan and daughter Chloe, I am so blessed for your unconditional love. I hope this will encourage you to never stop learning. iii Contributions My supervisor, Dr Sheldon Tobe, originally conceived of the research question for the meta- analysis. My program advisor committee members including Dr Josse and Dr Shah provided instrumental support and guidance on the protocol, methodology and interpretation of the study results. They also provided valuable feedback on this thesis. Lindsay Leduc was an independent reviewer for study screening and selection phase. Pat Donio was an independent reviewer for the data extraction phase. I am truly grateful for everyone’s dedication and collaboration. iv Table of Contents Table of Contents Acknowledgments.......................................................................................................................... iii Contributions.................................................................................................................................. iv Table of Contents .............................................................................................................................v List of Tables ............................................................................................................................... xix List of Figures ................................................................................................................................xx List of Abbreviations ................................................................................................................... xxi List of Appendices ...................................................................................................................... xxii INTRODUCTION ......................................................................................................................1 TYPE 2 DIABETES ...................................................................................................................3 2.1 EPIDEMIOLOGY ................................................................................................................3 2.1.1 Global .......................................................................................................................3 2.1.2 Canada......................................................................................................................3 2.1.3 United States of America .........................................................................................4 2.1.4 Rest of the World .....................................................................................................5 2.2 PATHOPHYSIOLOGY ........................................................................................................5 2.3 RISK FACTORS ...................................................................................................................6 2.3.1 Multifactorial ...........................................................................................................6 2.3.2 Adiposity/Obesity ....................................................................................................6 2.3.3 Diet ...........................................................................................................................7 2.3.4 Particulate Matter .....................................................................................................8 2.3.5 Race..........................................................................................................................9 2.3.6 Sex/Gender ...............................................................................................................9 2.4 COMPLICATIONS ............................................................................................................11 v 2.4.1 All-Cause Mortality ...............................................................................................12 2.4.2 Cardiovascular Disease ..........................................................................................12 2.4.3 Dementia ................................................................................................................13 2.4.4 Muscle Strength .....................................................................................................14 2.4.5 Falls ........................................................................................................................15 2.4.6 Fractures .................................................................................................................16 2.4.7 Sex-Gender Differences in Complications ............................................................18 2.4.8 Insurance / License / Employment .........................................................................19 2.5 COST ..................................................................................................................................19 2.5.1 Canada....................................................................................................................19 2.5.2 USA........................................................................................................................20 2.6 SUMMARY ........................................................................................................................20 MANAGEMENT ......................................................................................................................21 3.1 PREVENTION ....................................................................................................................21 3.1.1 Lifestyle Modification ...........................................................................................21 3.2 DIAGNOSIS .......................................................................................................................22 3.2.1 Prediabetes .............................................................................................................22 3.2.2 Diabetes..................................................................................................................23 3.3 GLYCEMIC TARGETS .....................................................................................................23 3.4 INTENSIVE VS LESS INTENSIVE GLYCEMIC CONTROL ........................................24 3.4.1 UKPDS ..................................................................................................................25 3.4.2 ADVANCE ............................................................................................................26 3.4.3 VADT ....................................................................................................................26 3.4.4 ACCORD ...............................................................................................................27 3.4.5 Meta-analysis of Intensive Glucose Control Trials ...............................................31 vi 3.4.6 Intensive Glucose Control in Acute Coronary Syndrome .....................................31
Load more

Recommended publications
  • Treatment Patterns, Persistence and Adherence Rates in Patients with Type 2 Diabetes Mellitus in Japan: a Claims- Based Cohort Study
    Open access Research BMJ Open: first published as 10.1136/bmjopen-2018-025806 on 1 March 2019. Downloaded from Treatment patterns, persistence and adherence rates in patients with type 2 diabetes mellitus in Japan: a claims- based cohort study Rimei Nishimura,1 Haruka Kato,2 Koichi Kisanuki,2 Akinori Oh,2 Shinzo Hiroi,2 Yoshie Onishi,3 Florent Guelfucci,4 Yukio Shimasaki2 To cite: Nishimura R, Kato H, ABSTRACT Strengths and limitations of this study Kisanuki K, et al. Treatment Objective To determine real-world trends in antidiabetic patterns, persistence and drug use, and persistence and adherence, in Japanese ► This retrospective evaluation of administrative adherence rates in patients patients with type 2 diabetes mellitus (T2DM). with type 2 diabetes mellitus claims data (2011–2015) using the Japan Medical Design Retrospective evaluation of administrative claims in Japan: a claims-based Data Center (JMDC) and Medical Data Vision (MDV) data (2011–2015) using the Japan Medical Data Center cohort study. BMJ Open databases was conducted to determine real-world (JMDC) and Medical Data Vision (MDV) databases. 2019;9:e025806. doi:10.1136/ trends in antidiabetic drug use, and persistence and Setting Analysis of two administrative claims databases bmjopen-2018-025806 adherence, in Japanese patients with type 2 dia- for Japanese patients with T2DM. betes mellitus (T2DM); 40 908 and 90 421 patients ► Prepublication history and Participants Adults (aged ≥18 years) with an International additional material for this were included from the JMDC and MDV databases, Classification of Diseases, 10th Revision code of T2DM and paper are available online. To respectively. at least one antidiabetic drug prescription.
    [Show full text]
  • Renato Wilberto Zilli Eficácia Em Longo Prazo Das
    RENATO WILBERTO ZILLI EFICÁCIA EM LONGO PRAZO DAS GLIFLOZINAS VERSUS GLIPTINAS NO TRATAMENTO DO DIABETES MELLITUS TIPO 2 APÓS FALÊNCIA DA METFORMINA COMO MONOTERAPIA: REVISÃO SISTEMÁTICA E METANÁLISE EM REDE Tese apresentada ao Programa de Ciências Médicas da Faculdade de Medicina da Universidade de São Paulo para obtenção do título de Doutor em Ciências. Área de Concentração: Processos Imunes e Infecciosos Orientador: Prof. Dr. Fabiano Pinheiro da Silva (Versão corrigida. Resolução CoPGr 6018/11, de 13 de outubro de 2011. A versão original está disponível na Biblioteca da FMUSP) São Paulo 2017 Dados Internacionais de Catalogação na Publicação (CIP) Preparada pela Biblioteca da Faculdade de Medicina da Universidade de São Paulo ©reprodução autorizada pelo autor Zilli, Renato Wilberto Eficácia em longo prazo das gliflozinas versus gliptinas no tratamento do diabetes mellitus tipo 2 após falência da metformina como monoterapia : revisão sistemática e metanálise em rede / Renato Wilberto Zilli ‐‐ São Paulo, 2017. Tese(doutorado)--Faculdade de Medicina da Universidade de São Paulo. Programa de Ciências Médicas. Área de concentração: Processos Imunes e Infecciosos. Orientador: Fabiano Pinheiro da Silva. Descritores: 1.Diabetes mellitus tipo 2 2.Metanálise 3.Terapia combinada 4.Falha de tratamento 5.Metformina 6.Inibidores da dipeptidil peptidase IV 7.Transportador 2 de glucose‐sódio/inibidores 8.Empagliflozina 9.Dapagliflozina 10.Saxagliptina USP/FM/DBD ‐302/17 Esta tese de doutorado está de acordo com as seguintes normas, em vigor no momento desta publicação: Referências: adaptado de International Committee of Medical Journals Editors (Vancouver). Guia de apresentação e dissertações, teses e monografias. Elaborado por Anneliese Cordeiro da Cunha, Maria Julia de A.L.
    [Show full text]
  • Comparison of Clinical Outcomes and Adverse Events Associated with Glucose-Lowering Drugs in Patients with Type 2 Diabetes: a Meta-Analysis
    Online Supplementary Content Palmer SC, Mavridis D, Nicolucci A, et al. Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes: a meta-analysis. JAMA. doi:10.1001/jama.2016.9400. eMethods. Summary of Statistical Analysis eTable 1. Search Strategies eTable 2. Description of Included Clinical Trials Evaluating Drug Classes Given as Monotherapy eTable 3. Description of Included Clinical Trials Evaluating Drug Classes Given as Dual Therapy Added to Metformin eTable 4. Description of Included Clinical Trials Evaluating Drug Classes Given as Triple Therapy When Added to Metformin Plus Sulfonylurea eTable 5. Risks of Bias in Clinical Trials Evaluating Drug Classes Given as Monotherapy eTable 6. Risks of Bias in Clinical Trials Evaluating Drug Classes Given as Dual Therapy Added to Metformin eTable 7. Risks of Bias in Clinical Trials Evaluating Drug Classes Given as Triple Therapy When Added to Metformin plus Sulfonylurea eTable 8. Estimated Global Inconsistency in Networks of Outcomes eTable 9. Estimated Heterogeneity in Networks eTable 10. Definitions of Treatment Failure Outcome eTable 11. Contributions of Direct Evidence to the Networks of Treatments eTable 12. Network Meta-analysis Estimates of Comparative Treatment Associations for Drug Classes Given as Monotherapy eTable 13. Network Meta-analysis Estimates of Comparative Treatment Associations for Drug Classes When Used in Dual Therapy (in Addition to Metformin) eTable 14. Network Meta-analysis Estimates of Comparative Treatment Effects for Drug Classes Given as Triple Therapy eTable 15. Meta-regression Analyses for Drug Classes Given as Monotherapy (Compared With Metformin) eTable 16. Subgroup Analyses of Individual Sulfonylurea Drugs (as Monotherapy) on Hypoglycemia eTable 17.
    [Show full text]
  • Trelagliptin (SYR-472, Zafatek), Novel Once- Weekly Treatment for Type 2 Diabetes, Inhibits Dipeptidyl Peptidase-4 (DPP-4) Via a Non-Covalent Mechanism
    RESEARCH ARTICLE Trelagliptin (SYR-472, Zafatek), Novel Once- Weekly Treatment for Type 2 Diabetes, Inhibits Dipeptidyl Peptidase-4 (DPP-4) via a Non-Covalent Mechanism Charles E. Grimshaw1*, Andy Jennings2, Ruhi Kamran1, Hikaru Ueno3, Nobuhiro Nishigaki3, Takuo Kosaka4, Akiyoshi Tani4, Hiroki Sano5, Yoshinobu Kinugawa5, Emiko Koumura5, Lihong Shi1¤, Koji Takeuchi3 a11111 1 Enzymology and Biophysical Chemistry, Takeda California, Inc., San Diego, California, United States of America, 2 Computational Sciences and Crystallography, Takeda California, Inc., San Diego, California, United States of America, 3 Cardiovascular and Metabolic Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan, 4 Bio-Molecular Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan, 5 Takeda Development Center Japan, Takeda Pharmaceutical Company Limited, Osaka, Japan OPEN ACCESS ¤ Current address: Celgene Quanticel Research, San Diego, California, United States of America * Citation: Grimshaw CE, Jennings A, Kamran R, [email protected] Ueno H, Nishigaki N, Kosaka T, et al. (2016) Trelagliptin (SYR-472, Zafatek), Novel Once-Weekly Treatment for Type 2 Diabetes, Inhibits Dipeptidyl Peptidase-4 (DPP-4) via a Non-Covalent Mechanism. Abstract PLoS ONE 11(6): e0157509. doi:10.1371/journal. Trelagliptin (SYR-472), a novel dipeptidyl peptidase-4 inhibitor, shows sustained efficacy by pone.0157509 once-weekly dosing in type 2 diabetes patients. In this study, we characterized in vitro proper- Editor: Alessandro Giuffrè, National Research ties of trelagliptin, which exhibited approximately 4- and 12-fold more potent inhibition against Council of Italy (CNR), ITALY human dipeptidyl peptidase-4 than alogliptin and sitagliptin, respectively, and >10,000-fold Received: February 10, 2016 selectivity over related proteases including dipeptidyl peptidase-8 and dipeptidyl peptidase-9.
    [Show full text]
  • A Review on Impact of Glucose-Lowering Therapies on Cardiovascular System in Type 2 Diabetes Mellitus Patients
    World Journal of Advanced Research and Reviews, 2020, 07(01), 162–173 World Journal of Advanced Research and Reviews e-ISSN: 2581-9615, Cross Ref DOI: 10.30574/wjarr Journal homepage: https://www.wjarr.com (REVIEW ARTICLE) A review on impact of glucose-lowering therapies on cardiovascular system in type 2 diabetes mellitus patients Khatoon Ruquiyyah and Hoda Quaisul * Lloyd Institute of Management and Technology (Pharm), Plot No. 11, Knowledge Park-2, Greater Noida, India. Publication history: Received on 01 July 2020; revised on 10 July 2020; accepted on 12 July 2020 Article DOI: https://doi.org/10.30574/wjarr.2020.7.1.0242 Abstract The prevalence of diabetes mellitus (DM), a well-renowned metabolic diseases that comes under Top-10 lethal and incurable disease of the world, is increasing day by day. It is well-reported that the mortality rate of diabetic patients due to comorbidities is higher. Diabetic patients suffer from several cardiovascular events and such risk increases with an intermediate metabolite HbA1c. Control in HbA1c and lowering it does not appear to yield the same benefit on macrovascular endpoints, as observed for microvascular endpoints. Moreover, secondary diseases caused by diabetes mellitus are many and diabetic patients have been found to be more susceptible to diseases like cardiac injury. For instance, rosiglitazone has been found to cause myocardial infarction and ultimately leads to heart failure. Glucagon like Peptide -1 (GLP-1) agonists and sodium- glucose co-transporter 2 (SGLT2) inhibitors causes several cardiac side effects like myocardial infarction and stroke. In this concern, USFDA officially announced in2008 that all new glucose-lowering agents should be tested for its cardiac safety.
    [Show full text]
  • Dipeptidyl Peptidase IV (DPP4) Inhibitors As Potential
    Supporting Materials Drug repurposing: Dipeptidyl peptidase IV (DPP4) inhibitors as potential agents to treat SARS-CoV-2 (2019-nCov) infection Praveen P. N. Rao 1*, Amy Trinh Pham 1, Arash Shakeri 1, Amna El Shatshat 1, Yusheng Zhao 1, Rahul C. Karuturi 1 and Ahmed A. Hefny 1 School of Pharmacy, University of Waterloo, Health Sciences Campus, 200 University Ave West, Waterloo, Ontario N2L 3G1, Canada *Corresponding author Praveen P. N. Rao, School of Pharmacy, Health Sciences Campus, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1, phone: 519-888-4567; ext: 21317; email: [email protected] Contents 1. Figure S1: Binding modes of DPP4 inhibitors anagliptin (A), alogliptin (B), trelagliptin (C) and sitagliptin (D) in the SARS-CoV-2 Mpro protomer 2. Figure S2: Binding modes of DPP4 inhibitors teneligliptin (A) and gosogliptin (B) in the SARS-CoV-2 Mpro protomer 3. Figure S3: Electrostatic surface potential map of SARS-CoV-2 Mpro protomer (A) and (B) dimer 4. Figure S4: Binding modes of DPP4 inhibitors gemigliptin, linagliptin and evogliptin in the MERS-CoV 3CLpro dimer 5. Figure S5: Pharmacophore model to design SARS-CoV-2 Mpro dimer inhibitors based on the docked poses of DPP4 inhibitors - gemigliptin, linagliptin and evogliptin 6. Figure S6: 2D Interaction map of linagliptin in the active sites of the serine protease DPP4 and cysteine protease SARS-CoV-2 Mpro 7. Table S1: Physicochemical properties of DPP4 inhibitors and the SARS-CoV-2 Mpro dimer inhibitor 1 1 Figure S1. Binding modes of DPP4 inhibitors anagliptin (A), alogliptin (B), trelagliptin (C) and sitagliptin (D) in the SARS-CoV-2 Mpro protomer (PDB ID: 6Y2F).
    [Show full text]
  • Implications Current Drugs for Type 2 Diabetes Mellitus
    Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus Abd A. Tahrani1,2, Anthony H. Barnett1,2 and Clifford J. Bailey3 Abstract |6[RG|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|TGEGRVQT ).24 CIQPKUVUFKRGRVKF[N RGRVKFCUG| &22 KPJKDKVQTUCPFUQFKWOINWEQUGEQVTCPURQTVGT|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ype 2 diabetes mellitus (T2DM) is a global epidemic with an dysfunction, as
    [Show full text]
  • Dipeptidyl Peptidase-4 Inhibitors and the Risk of Heart Failure: a Systematic Review and Meta-Analysis
    CMAJ OPEN Research Dipeptidyl peptidase-4 inhibitors and the risk of heart failure: a systematic review and meta-analysis Subodh Verma MD PhD, Ronald M. Goldenberg MD, Deepak L. Bhatt MD MPH, Michael E. Farkouh MD MSc, Adrian Quan MPhil, Hwee Teoh PhD, Kim A. Connelly MBBS PhD, Lawrence A. Leiter MD, Jan O. Friedrich MD DPhil Abstract Background: Given recent discrepant results from randomized controlled trials (RCTs), we examined the totality of RCT evidence assessing the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and heart failure. Methods: MEDLINE, Embase and ClinicalTrials.gov were searched without language restrictions to August 2016 for RCTs compar- ing DPP-4 inhibitors to placebo or no therapy for a period of 24 weeks or more. We included all heart failure outcomes when listed either as a serious adverse event or adverse event. Pooled analyses used random-effects. Results: We identified 100 RCTs (n = 79 867) — 3 large cardiovascular-safety RCTs (SAVOR-TIMI 53[saxagliptin]/n = 16 492, EXAMINE[alogliptin]/n = 5380, and TECOS[sitagliptin]/n = 14 735), and 97 smaller RCTs with a primary outcome that was usually change in glycated hemoglobin. Virtually all RCTs were high-quality, multicentre, placebo-controlled trials. A total of 96% (1192/1244) of heart failure events were prespecified, blindly adjudicated and required hospital admission. Pooled results suggested a 13% increase in heart failure (relative risk [RR] 1.13, 95% confidence interval [CI] 1.01–1.26, I2 = 0%; 32 RCTs, n = 54 640, 1244 events). When including only the 3 large RCTs, the increase was similar, but not significant (RR 1.14, 95% CI 0.97–1.32; 3 RCTs, n = 36 543, 1169 adjudicated events; number needed to harm 246) owing to heterogeneity (I2 = 42%), which lead to wider CIs, because SAVOR- TIMI 53 showed increased heart failure (RR 1.26, 95% CI 1.06–1.49) and TECOS showed no effect (RR 1.00, 95% CI 0.83–1.19).
    [Show full text]
  • Title Long-Term Safety and Efficacy of a Novel Once-Weekly Oral Trelagliptin As Monotherapy Or in Combination with an Existing O
    Long-term safety and efficacy of a novel once-weekly oral trelagliptin as monotherapy or in combination with an existing Title oral antidiabetic drug in patients with type 2 diabetes mellitus: A 52-week open-label, phase 3 study Inagaki, Nobuya; Sano, Hiroki; Seki, Yoshifumi; Kuroda, Author(s) Shingo; Kaku, Kohei Citation Journal of Diabetes Investigation (2016), 7(5): 718-726 Issue Date 2016-09 URL http://hdl.handle.net/2433/215204 © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd; This is an open access article under the terms of the Creative Commons Right Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Type Journal Article Textversion publisher Kyoto University CLINICAL TRIAL Long-term safety and efficacy of a novel once- weekly oral trelagliptin as monotherapy or in combination with an existing oral antidiabetic drug in patients with type 2 diabetes mellitus: A 52-week open-label, phase 3 study Nobuya Inagaki1*, Hiroki Sano2,YoshifumiSeki2, Shingo Kuroda2, Kohei Kaku3 1Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, 2Takeda Development Center Japan, Takeda Pharmaceutical Company Limited, Osaka, and 3Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan Keywords ABSTRACT Long-term safety and efficacy, Aims/Introduction: Trelagliptin is a novel once-weekly oral dipeptidyl peptidase-4 inhi- Trelagliptin, Type 2 diabetes mellitus bitor for type 2 diabetes mellitus that was first approved in Japan.
    [Show full text]
  • Report on Investigation Results
    Pharmaceuticals and Medical Devices Agency This English version is intended to be a reference material for the convenience of users. In the event of inconsistency between the Japanese original and this English translation, the former shall prevail. Report on Investigation Results August, 21, 2019 Pharmaceuticals and Medical Devices Agency I. Summary of drug [Branded name] Zafatek Tablets 25 mg, 50mg, 100 mg [Non-proprietary name] Trelagliptin succinate [Approval holder] Takeda Pharmaceutical Company Limited. [Indications] Type 2 diabetes mellitus [Dosage and administration] The usual adult dosage is 100 mg of trelagliptin orally administered once weekly. [Investigating office] Office of Pharmacovigilance I II. Investigation background Zafatek Tablets (hereinafter referred to as “Zafatek”) 50 mg and 100 mg is an oral hypoglycemic agent that inhibits dipeptidyl peptidase-4 (hereinafter “DPP-4”) and is administered once weekly. Zafatek was approved for marketing with an indication for “type 2 diabetes mellitus” in March, 2015 in Japan. In the clinical pharmacology study of Zafatek 50 mg and 100 mg (101 Study) conducted up to the products’ application for marketing, the plasma concentration-area under the concentration curve (hereinafter, “AUC”) of unchanged trelagliptin after a single dose of Zafatek at 50 mg was 3.01 fold and 3.68 fold in patients with severe renal impairment and end stage renal failure, respectively, in comparison to that of patients with normal renal function. Based on this result, the marketing authorization holder (hereinafter,
    [Show full text]
  • Canagliflozin, Dapagliflozin and Empagliflozin Monotherapy for Treating Type 2 Diabetes: Systematic Review and Economic Evaluation
    HEALTH TECHNOLOGY ASSESSMENT VOLUME 21 ISSUE 2 JANUARY 2017 ISSN 1366-5278 Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation Rhona Johnston, Olalekan Uthman, Ewen Cummins, Christine Clar, Pamela Royle, Jill Colquitt, Bee Kang Tan, Andrew Clegg, Saran Shantikumar, Rachel Court, J Paul O’Hare, David McGrane, Tim Holt and Norman Waugh DOI 10.3310/hta21020 Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation Rhona Johnston,1 Olalekan Uthman,2 Ewen Cummins,1 Christine Clar,3 Pamela Royle,2 Jill Colquitt,4 Bee Kang Tan,2 Andrew Clegg,5 Saran Shantikumar,2 Rachel Court,2 J Paul O’Hare,2 David McGrane,6 Tim Holt7 and Norman Waugh2* 1McMDC, Harrogate, UK 2Warwick Evidence, Division of Health Sciences, University of Warwick, Coventry, UK 3Berlin, Germany 4Effective Evidence, Waterlooville, UK 5University of Central Lancashire, Preston, UK 6Queen Elizabeth University Hospital, Glasgow, UK 7University of Oxford, Oxford, UK *Corresponding author Declared competing interests of authors: David McGrane has spoken at educational meetings sponsored by AstraZeneca, Eli Lilly, Sanofi, MSD, Takeda Pharmaceutical Company, Novo Nordisk, Janssen, and has served on Advisory Boards for Eli Lilly, Sanofi, Novo Nordisk. J Paul O’Hare has received lecture fees, advisory board meeting fees, and grants for research from Novo Nordisk and Sanofi. All fees are paid through University of Warwick to fund access to insulin projects in sub-Saharan Africa. Published January 2017 DOI: 10.3310/hta21020 This report should be referenced as follows: Johnston R, Uthman O, Cummins E, Clar C, Royle P, Colquitt J, et al.
    [Show full text]
  • 2011/064352 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date , , ,, , 3 June 2011 (03.06.2011) 201 1/064352 Al (51) International Patent Classification: (74) Agents: HAMMANN, Heinz et al; Boehringer Ingel A61K 31/155 (2006.01) A61K 31/519 (2006.01) heim GmbH, Corporate Patents, Binger Str. 173, 55216 A61K 31/44 (2006.01) A61K 45/06 (2006.01) Ingelheim am Rhein (DE). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/EP20 10/068349 kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, (22) International Filing Date: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, 26 November 2010 (26.1 1.2010) DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (25) Filing Language: English HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (26) Publication Language: English ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, (30) Priority Data: NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, 09177418.2 27 November 2009 (27.1 1.2009) EP SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, 10166714.5 2 1 June 2010 (21 .06.2010) EP TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicant (for all designated States except US): (84) Designated States (unless otherwise indicated, for every BOEHRINGER INGELHEIM INTERNATIONAL kind of regional protection available): ARIPO (BW, GH, GMBH [DE/DE]; Binger Str.
    [Show full text]