The Unique Pharmacological and Pharmacokinetic Profile of Teneligliptin: Implications for Clinical Practice

Abstract

Teneligliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that was approved for the treatment of type 2 diabetes mellitus (T2DM) in Japan and Korea and is being researched in several countries. Teneligliptin is a potent, selective, and long-lasting DPP-4 inhibitor with a t ½ of approximately 24 h and unique pharmacokinetic properties: it is metabolized by cytochrome P450 (CYP) 3A4 and flavin-containing monooxygenase 3 (FMO3), or excreted from the kidney in an unchanged form. Because of its multiple elimination pathways, dose adjustment is not needed in patients with hepatic or renal impairment, and it is considered to have a low potential for drug–drug interactions. Clinical studies and postmarketing surveillance show that teneligliptin, administered as monotherapy and/or in combination with antihyperglycemic agents, is effective and well tolerated in T2DM patients, including in elderly patients and those with renal impairment. Furthermore, teneligliptin has antioxidative properties, which induce the antioxidant cascade, as well as ·OH scavenging properties. In addition, it has shown endothelial protective effects in several non-clinical and clinical studies. From its unique profile and clinical data, teneligliptin represents a potential therapeutic option in a wide variety of patients, including elderly diabetic patients and those with renal impairment. The fixed-dose combination (FDC) tablet of teneligliptin and canagliflozin has been approved in Japan; this is the first FDC tablet of a DPP-4 inhibitor and sodium glucose co-transporter 2 inhibitor in Japan, and the third globally. The FDC tablet may also provide additional prescribing and adherence benefits.

Long-Term, Real-World Safety and Efficacy of Teneligliptin: A Post-Marketing Surveillance of More Than 10,000 Patients with Type 2 Diabetes in Japan

“…This surveillance revealed that the incidence of any ADRs in teneligliptin-treated patients was 3.85% and serious ADRs in 1.09%. Of note, the overall rate of ADRs did not exceed the rates observed in clinical trials (9.48% of 1645 patients) [23] or over 1 year in clinical trials (6.7-18.9%) [13] in Japan. The safety profile of teneligliptin in this surveillance was generally similar to those reported for other DPP4 inhibitors [30][31][32][33][34][35][36].…”

“…Teneligliptin, a DPP4 inhibitor, was approved in Japan in 2012 and subsequently in Korea in 2014 [13]. The clinical trials for teneligliptin demonstrated its efficacy and safety as monotherapy [14,15] or in combination with oral antidiabetic agents or insulin [16][17][18][19][20][21][22].…”

“…On the basis of the approved label [23], if the prescribing physician thinks the patient's glycaemic control is inadequate, the dose of teneligliptin can be increased to 40 mg once daily with close monitoring of the patient. Teneligliptin can be used without the need for dose adjustment in patients with T2DM and impaired renal function, including those on dialysis, because of its unique pharmacokinetic profile involving elimination by multiple pathways: hepatic metabolism by cytochrome P450 3A4 and flavin-containing monooxygenase 3 or excretion in an unchanged form by the kidney [13].…”

Overview of the Clinical Pharmacology of Ertugliflozin, a Novel Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor

“…Dapagliflozin, canagliflozin, and empagliflozin also have approved FDCs with metformin [16]. In addition, dapagliflozin and empagliflozin are widely available as FDCs with saxagliptin and linagliptin, respectively [16]; a canagliflozin/ teneligliptin FDC has recently been approved in Japan [17]. This review will focus primarily on the phase I pharmacokinetics (PK) and pharmacodynamics (PD) of the ertugliflozin stand-alone therapy.…”

Long-Term Safety and Efficacy of Teneligliptin in Elderly Patients with Type 2 Diabetes: Subgroup Analysis of a 3-Year Post-Marketing Surveillance in Japan

“…Teneligliptin, a DPP4 inhibitor, is currently approved in Japan and Korea for the treatment of T2DM [ 9 – 11 ]. In Japan, it is prescribed at a starting dose of 20 mg once daily, but its dose can be increased to 40 mg once daily if the glucose-lowering effect of 20 mg once daily is insufficient.…”