Linagliptin: from bench to bedside

Abstract

PurposeThe 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.SummaryClinical 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.ConclusionIn 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.

Kidney Disease End Points in a Pooled Analysis of Individual Patient–Level Data From a Large Clinical Trials Program of the Dipeptidyl Peptidase 4 Inhibitor Linagliptin in Type 2 Diabetes

“…19 All patients provided written informed consent. Local ethics committees/institutional review boards reviewed and approved all study protocols.…”

Dipeptidyl peptidase-4 inhibitor linagliptin attenuates neointima formation after vascular injury

“…Pooled analysis of clinical studies revealed that sitagliptin has a good tolerability in elderly patients with type 2 diabetes [8], with a lower rate of cardiovascular-related events compared with sulphonylurea [9]. Linagliptin is a newly identified, biliary excreted DPP-4 inhibitor, which has recently been approved as a once-daily oral glucose-lowering agent [10]. Similar to sitagliptin, the cardiovascular safety of linagliptin has been suggested to be acceptable in high-risk patients [11], and its efficacy and safety are acceptable as an add-on therapy to metformin and sulphonylurea [12].…”

Preferential prescribing of linagliptin in type 2 diabetes patients in an expanded post‐marketing surveillance study in Japan

“…The expansion of the linagliptin Japan PMS study to include collection of baseline characteristics in patients who were eligible for linagliptin treatment, but initiating GLDs other than linagliptin, showed the spectrum of patients receiving linagliptin, and enabled the identification of preferential prescribing of linagliptin in patients with cardiac, vascular, renal/urinary and metabolism/nutritional disorders. Although preferential prescribing could be anticipated based on pharmacokinetic data (indicating that dose adjustment is not required) and clinical trial data reflected in the prescribing information (showing safety and efficacy in these patients), this phenomenon can only be determined in a real‐world data study with comparator data.…”

“…The first DPP‐4 inhibitor was launched in Japan in 2009, and has since been followed by eight other drugs from this class, including linagliptin in 2011. Unlike many other glucose‐lowering drugs (GLDs), linagliptin can be administered in patients with renal or hepatic impairment without adjustment of the standard clinical dosage (5 mg once daily). Clinical trials have confirmed the efficacy of linagliptin in patients with kidney disease, liver disease and cardiovascular disease.…”