Linagliptin: from bench to bedside

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.

Keywords:

• dipeptidyl peptidase-4 inhibitor
• linagliptin
• type 2 diabetes

Acknowledgments

The author was fully responsible for all content and editorial decisions, was involved at all stages of manuscript development, and has approved the final version of the review that reflects the author’s interpretation and conclusions. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Michael P Bennett, PhD, and Marissa Buttaro, MPH, of Envision Scientific Solutions during the preparation of this review. Boehringer Ingelheim was given the opportunity to check the data used in the manuscript for factual accuracy only.

Disclosure

The author has declared no potential conflicts of interest.