Teneligliptin: a DPP-4 inhibitor for the treatment of type 2 diabetes

Abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitors have recently emerged as a new class of antidiabetic that show favorable results in improving glycemic control with a minimal risk of hypoglycemia and weight gain. Teneligliptin, a novel DPP-4 inhibitor, exhibits a unique structure characterized by five consecutive rings, which produce a potent and long-lasting effect. Teneligliptin is currently used in cases showing insufficient improvement in glycemic control even after diet control and exercise or a combination of diet control, exercise, and sulfonylurea- or thiazolidine-class drugs. In adults, teneligliptin is orally administered at a dosage of 20 mg once daily, which can be increased up to 40 mg per day. Because the metabolites of this drug are eliminated via renal and hepatic excretion, no dose adjustment is necessary in patients with renal impairment. The safety profile of teneligliptin is similar to those of other available DPP-4 inhibitors. However, caution needs to be exercised when administering teneligliptin to patients who are prone to QT prolongation. One study has reported that the postprandial blood glucose-lowering effects of teneligliptin administered prior to breakfast were sustained throughout the day, and the effects observed after dinner were similar to those observed after breakfast or lunch. Thus, although clinical data for this new drug are limited, this drug shows promise in stabilizing glycemic fluctuations throughout the day and consequently suppressing the progression of diabetic complications. However, continued evaluation in long-term studies and clinical trials is required to evaluate the efficacy and safety of the drug as well as to identify additional indications for its clinical use.

Teneligliptin: Heralding Change in Type 2 Diabetes

“…The maximum percentage of the inhibition in plasma DPP-4 activity was achieved within 2 hours after administration and was 81.3% and 89.7% with Teneligliptin 10 and 20 mg, respectively [10]. The percentage inhibition of DPP-4 activity at 24 hrs, after administration was 53.1% in Teneligliptin 10 mg group & 61.8% in Teneligliptin 20 mg group.…”

“…The active plasma GLP-1 concentration was higher after Teneligliptin administration than placebo throughout the day, even at 24 hours after administration. The AUC 0-2h values for the active GLP-1 concentration after breakfast, lunch and dinner were 8.0, 8.4 and 7.8 pmol⋅h/L respectively, in Teneligliptin 10 mg group and 8.3, 7.9, and 8.6 pmol⋅h/L respectively, in Teneligliptin 20 mg group [10]. As compared to Teneligliptin 10 mg group, increase in AUC 0-2h for active GLP-1 concentration was slightly greater after dinner in Teneligliptin 20 mg group.…”

“…The dose of Teneligliptin was increased to 40 mg in patients with HbA1c levels greater than 7.3% at any time after week 24. The mean body weight change of the patients at week 52 (mean ± SD) was +0.18 ± 2.14 kg (p = 0.3254), which indicated that the effect of Teneligliptin on body weight was neutral [10].…”

“…In vitro, Teneligliptin is a weak inhibitor of CYP2D6, CYP3A4 and FMO, but shows no inhibitory effect on CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C8/9, CYP2C19 and CYP2E1 [10] [26]. Teneligliptin does not induce CYP3A4 or CYP1A2 [10] [26].…”

“…In QT/ QTc studies, a supratherapeutic dose of Teneligliptin (160 mg/day) produced slight prolongation of the QTc interval which was detected temporally at the high concentrations of the drug (around tmax level). Teneligliptin at the daily dose of up to 40 mg (maximum dose used in clinical practice) is unlikely to cause clinically significant QTc interval prolongation [10].…”