The pharmacokinetics and pharmacodynamics of alogliptin in children, adolescents, and adults with type 2 diabetes mellitus

Abstract

PurposeThe aim of this study is to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of a single 12.5- or 25-mg dose of alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in pediatric (children and adolescents) and adult subjects with type 2 diabetes mellitus (T2DM).MethodsA randomized, open-label, multicenter study was conducted in pediatric and adult subjects. Subjects in two pediatric groups (children and adolescents) were randomized 1:1 to receive a single oral dose of alogliptin 12.5 or 25 mg, respectively; all gender- and race-matched adult subjects received alogliptin 25 mg. Blood and urine samples were collected at prespecified time points for PK/PD analyses. A PK/PD model was developed using data from the study for steady-state simulations. Safety was also assessed.ResultsIn pediatric subjects receiving the 25-mg dose, the mean alogliptin peak plasma concentrations (Cmax) and AUC0-inf values were 26 and 23% lower, respectively, than in adults receiving the 25-mg dose, but maximum observed DPP-4 inhibition effect (Emax) and AUEC0–24 values were similar to those in adults. In pediatric subjects receiving the 12.5-mg dose, the mean alogliptin Cmax and AUC0-inf values were 58 and 54% lower, respectively, than those in adults, hence Emax and AUEC0–24 values were also lower by 11 and 17%, respectively. The PK/PD model simulated data were consistent with study results. No safety concern was found.ConclusionsA 25-mg dose of alogliptin in pediatric subjects achieved alogliptin exposures and DPP-4 inhibition similar to those in adult T2DM patients without safety concerns; therefore, this dose is recommended for a pediatric phase 3 trial.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-016-2175-1) contains supplementary material, which is available to authorized users.

Systematic Review of Efficacy and Safety of Newer Antidiabetic Drugs Approved from 2013 to 2017 in Controlling HbA1c in Diabetes Patients

“…Despite decreased secretion, GLP-1 still keeps its glucoregulatory activity. Therefore, concentrations of active incretions such as GIP and GLP-1 increase due to the inhibition of DPP-4 activity [ 18 ]. These two incretins can activate the pancreatic β cells to secrete insulin, and also promote proliferation of the beta-cell and cytoprotects to improve homeostasis of glucose.…”

“…Alogliptin, a DDP-4 inhibitor has advantage over other antidiabetic agents as it does not produce weight gain [ 66 ], and its ability to inhibit atherosclerosis and inflammation [ 19 ]. Alogliptin helps to improve glycemic control in adults with T2DM together with diet and exercise plan [ 18 ]. It can produce rapid and sustained DPP-4 inhibition and improve both postprandial and fasting plasma glucose.…”

“…It can produce rapid and sustained DPP-4 inhibition and improve both postprandial and fasting plasma glucose. After 12 to 26 weeks of treatment in adult patients, the HbA1c has been reduced by approximately 0.5% to 1% [ 18 ]. However, many studies proved that it brings better glycemic control when combined with other non-DPP-4 inhibitor antidiabetic agents, instead of alogliptin alone [ 18 , 67 ].…”

“…After 12 to 26 weeks of treatment in adult patients, the HbA1c has been reduced by approximately 0.5% to 1% [ 18 ]. However, many studies proved that it brings better glycemic control when combined with other non-DPP-4 inhibitor antidiabetic agents, instead of alogliptin alone [ 18 , 67 ]. A primary analysis had demonstrated the superiority of combination of alogliptin and metformin OD over the use of alogliptin alone.…”

Do novel drugs for diabetes help in COVID‐19? Another brick in the wall?

“…4 Furthermore, as shown in a small proof-of-concept study, children were slightly less sensitive to DPP4 inhibitoralogliptin, compared to adults, possibly due to the increased level of soluble DPP4. 5 One can speculate that DPP4 inhibitors could block an alternative entry site for SARS-CoV-2, thus being beneficial for COVID-19 patients. On the other hand, while binding also to soluble DPP4, they could decrease its putative neutralizing/antiviral potential.…”