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      Novel Hypoglycaemic Agents: Considerations in Patients with Chronic Kidney Disease

      *

      Nephron Clinical Practice

      S. Karger AG

      Type 2 diabetes, Renal impairment, Drug treatment

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          Abstract

          One of the commonest complications of type 2 diabetes is renal disease. Treatment guidelines emphasise the need for tight glycaemic control to reduce the development of future complications; however, with the development of renal impairment, the benefit of tight glycaemic control must be weighed against the potential for adverse effects from drugs or their metabolites which may accumulate. In this article, the glucose-lowering drugs used in the management of type 2 diabetes are reviewed, with particular emphasis on newer guidelines and agents.

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          Most cited references 5

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          Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial.

          Agonists of the glucagon-like peptide-1 (GLP-1) receptor provide pharmacological levels of GLP-1 activity, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors increase concentrations of endogenous GLP-1 and glucose-dependent insulinotropic polypeptide. We aimed to assess the efficacy and safety of the human GLP-1 analogue liraglutide versus the DPP-4 inhibitor sitagliptin, as adjunct treatments to metformin, in individuals with type 2 diabetes who did not achieve adequate glycaemic control with metformin alone. In this parallel-group, open-label trial, participants (aged 18-80 years) with type 2 diabetes mellitus who had inadequate glycaemic control (glycosylated haemoglobin [HbA(1c)] 7.5-10.0%) on metformin (>or=1500 mg daily for >or=3 months) were enrolled and treated at office-based sites in Europe, the USA, and Canada. Participants were randomly allocated to receive 26 weeks' treatment with 1.2 mg (n=225) or 1.8 mg (n=221) subcutaneous liraglutide once daily, or 100 mg oral sitagliptin once daily (n=219). The primary endpoint was change in HbA(1c) from baseline to week 26. The efficacy of liraglutide versus sitagliptin was assessed hierarchically by a non-inferiority comparison, with a margin of 0.4%, followed by a superiority comparison. Analyses were done on the full analysis set with missing values imputed by last observation carried forward; seven patients assigned to liraglutide did not receive treatment and thus did not meet criteria for inclusion in the full analysis set. This trial is registered with ClinicalTrials.gov, number NCT00700817. Greater lowering of mean HbA(1c) (8.5% at baseline) was achieved with 1.8 mg liraglutide (-1.50%, 95% CI -1.63 to -1.37, n=218) and 1.2 mg liraglutide (-1.24%, -1.37 to -1.11, n=221) than with sitagliptin (-0.90%, -1.03 to -0.77, n=219). Estimated mean treatment differences for liraglutide versus sitagliptin were -0.60% (95% CI -0.77 to -0.43, p<0.0001) for 1.8 mg and -0.34% (-0.51 to -0.16, p<0.0001) for 1.2 mg liraglutide. Nausea was more common with liraglutide (59 [27%] patients on 1.8 mg; 46 [21%] on 1.2 mg) than with sitagliptin (10 [5%]). Minor hypoglycaemia was recorded in about 5% of participants in each treatment group. Liraglutide was superior to sitagliptin for reduction of HbA(1c), and was well tolerated with minimum risk of hypoglycaemia. These findings support the use of liraglutide as an effective GLP-1 agent to add to metformin. Novo Nordisk. Copyright 2010 Elsevier Ltd. All rights reserved.
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            Helicobacter pylori eradication in long-term users of non-steroidal anti-inflammatory drugs

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              Cardiovascular effects of the DPP-4 inhibitors.

              Type 2 Diabetes continues to rise in prevalence throughout the globe, and cardiovascular diseases remain the most common cause of morbidity and mortality among patients. Dipeptidyl-peptidase-4 (DPP-4) inhibitors are a newer class of oral anti-hyperglycemic agents whose effect is mediated through the incretin hormones, GLP-1 and GIP. In this review, we discuss the incretin system, DPP-4 inhibitors and their mechanism of action and, principally, the potential impact of DPP-4 inhibition on the cardiovascular system. Some pre-clinical data, small mechanistic studies and post-hoc analyses of randomized clinical trials suggest a possible beneficial effect on cardiovascular risk. However, the relationship between DPP-4 inhibition and actual cardiovascular outcomes remains unknown. We therefore also review ongoing large, randomized clinical trials examining this very question.
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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2014
                April 2014
                11 January 2014
                : 126
                : 1
                : 14-18
                Affiliations
                Department of Diabetes and Endocrinology, Derby Hospitals NHS FT, Derby, UK
                Author notes
                *Dr. Fran Game, Department of Diabetes and Endocrinology, Derby Hospitals NHS FT, Uttoxeter Road, Derby DE22 3NE (UK), E-Mail frances.game@nhs.net
                Article
                357680 Nephron Clin Pract 2014;126:14-18
                10.1159/000357680
                24434725
                © 2014 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Pages: 5
                Categories
                Minireview

                Cardiovascular Medicine, Nephrology

                Drug treatment, Renal impairment, Type 2 diabetes

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