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      Linagliptin: from bench to bedside

      review-article
      Drug Design, Development and Therapy
      Dove Medical Press
      dipeptidyl peptidase-4 inhibitor, linagliptin, type 2 diabetes

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          Abstract

          Purpose

          The nature of biomedical research affords a broad range of investigational topics at the preclinical stage, not all of which may be explored in subsequent clinical studies. To provide a comprehensive perspective on the physiologic effects of the dipeptidyl peptidase-4 inhibitor linagliptin, this review will discuss the results of both preclinical and clinical research, summarizing data describing outcomes associated with its use.

          Summary

          Clinical studies demonstrate an overall favorable safety profile, low risk for hypoglycemia, weight neutrality, primarily nonrenal clearance, and efficacy for glycosylated hemoglobin reduction, typically ranging from 0.6% to 0.8% depending on baseline levels. In addition to these characteristics, preclinical research on linagliptin has yielded several interesting findings such as improved wound healing, reduced hepatic fat content, decreased infarct size following myocardial infarction or intracranial stroke, and improved vascular function with decreased oxidative stress. In accordance with its preclinical profile, linagliptin is unique among available dipeptidyl peptidase-4 compounds because it does not require dose adjustment when used in patients with renal dysfunction. Reduction of albuminuria with linagliptin on top of inhibitors of the renin–angiotensin–aldosterone system in both preclinical and post hoc clinical analysis serves as the foundation for ongoing clinical trials.

          Conclusion

          In addition to its efficacy for glycemic control, current literature points to other potential opportunities associated with linagliptin therapy. These results warrant further investigation and underscore the importance of translational study based on findings from preclinical research. Moving forward, we can expect that future research on linagliptin and other incretin-based therapies will continue to expand their applications beyond the maintenance of glycemic control in patients with type 2 diabetes.

          Most cited references89

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          Inflammation in wound repair: molecular and cellular mechanisms.

          In post-natal life the inflammatory response is an inevitable consequence of tissue injury. Experimental studies established the dogma that inflammation is essential to the establishment of cutaneous homeostasis following injury, and in recent years information about specific subsets of inflammatory cell lineages and the cytokine network orchestrating inflammation associated with tissue repair has increased. Recently, this dogma has been challenged, and reports have raised questions on the validity of the essential prerequisite of inflammation for efficient tissue repair. Indeed, in experimental models of repair, inflammation has been shown to delay healing and to result in increased scarring. Furthermore, chronic inflammation, a hallmark of the non-healing wound, predisposes tissue to cancer development. Thus, a more detailed understanding in mechanisms controlling the inflammatory response during repair and how inflammation directs the outcome of the healing process will serve as a significant milestone in the therapy of pathological tissue repair. In this paper, we review cellular and molecular mechanisms controlling inflammation in cutaneous tissue repair and provide a rationale for targeting the inflammatory phase in order to modulate the outcome of the healing response.
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            The molecular biology of chronic wounds and delayed healing in diabetes.

            Wound healing is a complicated and integrated process. Although there is some tolerance in terms of redundancy and interrelated control mechanisms, pushing beyond such limits may contribute to delayed wound healing, and in extreme cases lead to chronic wounds/ulcers and thus potentially to lower extremity amputation. Diabetes is associated with such disruption in wound healing. Research in humans and in animal models has identified a large number of changes associated with diabetes at the molecular level in delayed wound healing and to a lesser extent in chronic diabetic ulcers. Better overall understanding of these changes and how they are interrelated would allow for specifically targeted treatment, thus ensuring improved quality of life for patients and providing savings to the high costs that are associated with all aspects of chronic diabetic ulcers. This review examines the work done at the molecular level on chronic diabetic ulcers, as well as considering changes seen in diabetes in general, both in humans and animal models, that may in turn contribute to ulcer formation.
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              Diabetes in older adults: a consensus report.

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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2014
                05 May 2014
                : 8
                : 431-446
                Affiliations
                Iatriko Palaiou Falirou Medical Center, Division of Diabetes, Athens, Greece
                Author notes
                Correspondence: John Doupis, Iatriko Palaiou Falirou Medical Center, Division of Diabetes, Areos 36. 175 62, P Faliro, Athens, Greece, Tel +30 210 989 2300, Email john.doupis@ 123456joslin.harvard.edu
                Article
                dddt-8-431
                10.2147/DDDT.S59523
                4018312
                24851042
                e4d0acc5-f2d9-4c29-8bae-096b639be879
                © 2014 Doupis. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                dipeptidyl peptidase-4 inhibitor,linagliptin,type 2 diabetes

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