Table 5.

Metabolism, elimination and drug interactions of current DPP-4 inhibitors currently on market.

Number	Name	Metabolism	Elimination	Drug interaction	Ref.
1	Sitagliptin	Half-life: 8–14 h; Tmax: 1–6 h; Enzymes: major CYP3A4, CYP2C8 made minor contribution	Majority of drug excreted through kidney; Clearance: 388 mL/min; 87% of drugs recovered in urine	Grapefruit interact with sitagliptin; No significant change in pharmacokinetic with lobeglitazone; No significant change in pharmacokinetic with tinospora cordifolia aqueous extract	137, 138, 139, 140, 141, 142, 143, 144
2	Saxagliptin	Half-life: 6.7  Active metabolite: 5-hydroxy saxagliptin; AUC: correlated with renal impairmen CYP3A4 and CYP3A5 played an important role in forming metabolites	74.9% in urine and 22.1% in feces; 24.0% saxagliptin and 44.1% 5-hydroxy saxagliptin; Mainly through renal and hepatic routes	Rifampicin would not significantly influence saxagliptin; Processed rhubarbs affect CYP450 enzymes, influencing saxagliptin	145, 146, 147, 148, 149, 150
3	Linagliptin	Cmax: 4 day Main metabolites: S-3-hydroxypiperidinly derivate; Enzymes: CYP3A4, aldo-keto reductases and some carbonyl reductases; Not have a linear dose-proportional AUC and Cmax	Excretion mainly through fecal; Most of the drugs maintained in its unchanged form	No significant pharmacokinetic change with fimasartan; Could be used together with digoxin; Inhibit OCT1 and OCT2 transporters	151, 152, 153, 154, 155, 156, 157
4	Alogliptin	Active metabolite: N-demethylation metabolite; Tmax: 1–2 h; Half-life: 12.5–21.1 h	Primarily eliminated in urine in the form of parent drug; Renal clearance: 8.6–13.6 L/h	Grapefruit interact with alogliptin; No significant change in pharmacokinetic with metformin or cimetidine	158, 159, 160, 161, 162
5	Vildagliptin	Major component in plasma: parent drug and a carboxylic acid derivate; Metabolic process: major through cyano group hydrolysis; Half-life: 1.32–2.43 h	Major excrete through urine; 22.6% maintained in the form of parent drug	limited interactions with CYP enzymes	163, 164, 165, 166, 167, 168
6	Gemigliptin	A total of 23 metabolites were observed in plasma; Major metabolite: hydroxylated metabolite; Cmax: 1.8 h; AUC increased proportionally with increasing of dosage; Terminal half-life: 17.1 h; dominantly metabolized by CYP3A4	90.5% recovered over 192 h major in urine; The parent drug is the most abundant component	Ketoconazole or rifampicin significantly change pharmacokinetics; Interactions with CYP3A4; No significant change in pharmacokinetics with glimepiride	169, 170, 171, 172, 173, 174
7	Teneligliptin	Major component: parent drug and thiazolidine-1-oxide derivative; Important enzymes: CYP3A4 and FMO3; Cmax and AUC increased in a dose dependent manner; elimination half-life: 24.2 h	Larger than 90% of teneligliptin could be excreted in 216 h; Excrete major in urine and feces; 65.6% goes through metabolism and 34.4% goes through excretion	No strong pharmacokinetics interactions with teneligliptin and canagliflozin; SLGT2 inhibitors have small interactions with teneligliptin	175, 176, 177, 178, 179
8	Omarigliptin	Tmax value could range from 0.75 to 4.0 h; Cmax and AUC almost in a dose dependent manner	74.4% of the drug in urine and 3.4% was observed in feces; Parent drug is the major component in urine; Renal excretion of the unchanged drug is the most important excretion method; Urinary excretion data is 1.6–2.7 L/h	Limited interactions with CYP450 enzymes and some key drug transporters.	180, 181, 182, 183, 184