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Linagliptin: from bench to bedside.

AbstractPURPOSE:
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.
AuthorsJohn Doupis
JournalDrug design, development and therapy (Drug Des Devel Ther) Vol. 8 Pg. 431-46 ( 2014) ISSN: 1177-8881 [Electronic] New Zealand
PMID24851042 (Publication Type: Journal Article, Review)
Chemical References
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Purines
  • Quinazolines
  • hemoglobin A1c protein, human
  • Linagliptin
Topics
  • Animals
  • Diabetes Mellitus, Type 2 (drug therapy)
  • Dipeptidyl-Peptidase IV Inhibitors (therapeutic use)
  • Glycated Hemoglobin (analysis)
  • Humans
  • Hypoglycemic Agents (therapeutic use)
  • Linagliptin
  • Purines (adverse effects, pharmacokinetics, pharmacology, therapeutic use)
  • Quinazolines (adverse effects, pharmacokinetics, pharmacology, therapeutic use)
  • Wound Healing (drug effects)

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