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. 2022 Nov 11;13(6):2383–2402. doi: 10.1016/j.apsb.2022.11.008

Table 4.

Metabolism, elimination and drug interactions of GLP-1 receptor agonists currently on market.

Number Name Metabolism Elimination Drug interaction Ref.
1 Exenatide Concentration in plasma: increased in a dose dependent manner;
Mean half-life: 3.3–4 h;
Tmax: 2.2 h		 Mainly degraded at kidney;
Completed degraded into peptides		 Delayed gastric emptying;
No significant effect with acetaminophen		 96, 97, 98, 99, 100
2 Liraglutide Mean half-life: 13.5 h;
Exposure increased in a dose dependent manner		 Cleaved by DPP-4 in the Ala 8–Glu 9 position of the N-terminus;
Product could be further degraded by NEP into several metabolites;
Rate of clearance is about 0.9–1.4 L/h;
Liraglutide degraded completely in body		 Liraglutide has small potential in reacting with CYP450;
Influence gastric emptying;
No pharmacokinetic interaction with insulin detemir		 101, 102, 103, 104, 105, 106
3 Albiglutide Metabolic process: urine ubiquitous proteolytic enzymes in vascular endothelium;
Half-life: five days;
Body clearance: 67 mL/h;
Maintain in a steady state after 4–5 days		 Degrade into small peptides and some single amino acids;
Could not be cleared in the glomeruli in normal state		 Safe in coadministration with digoxin or warfarin;
Have great influence on pharmacokinetics on simvastatin		 107, 108, 109, 110, 111, 112
4 Dulaglutide Cmax: 24–72 h;
Steady plasma concentration could maintain 2–4 weeks;
Elimination half-life: around 5 days		 Dulaglutide's excretion like general protein catabolism pathways;
Degrade into small polypeptides;
Not be eliminated through glomerular filtration or CYP450 enzymes		 Delayed gastric emptying;
No important pharmacokinetic interaction with digoxin, warfarin and atorvastatin		 113, 114, 115, 116
5 Lixisenatide Half-life: 2.7–4.3 h;
AUC and Cmax increased in a dose dependent manner		 Excreted like endogenous peptides;
CYP450 enzymes do not participate in metabolizing;
All the metabolites could be detected are polypeptides degraded from lixisenatide;
Main metabolites do not show any biological activities		 Delayed gastric emptying;
No need of adjusting dose with ethinylestradiol, levonorgestrel and atorvastatin		 44, 117, 118, 119, 120
6 Semaglutide A total of six metabolites were identified in human plasma;
Proteolytic cleavage in the peptide backbone area and beta-oxidation of the fatty acid side chain;
For oral given doses, median Tmax is 1.5 h, half-life is 1 week for the injection dose, Cmax within the range of 24–56 h.		 Metabolized prior to excretion slowly primarily in urine;
53% of the drug could be recovered in urine		 Delayed gastric emptying;
Potential increasing AUC of metformin;
Not increasing the half-life of lisinopril and warfarin.		 121, 122, 123, 124, 125, 126, 127, 128
7 Tirzepatide Catabolism of the peptide backbone and β-oxidation of the di-acid chain;
Main metabolites in circulation: parent drug, accounting to higher than 80%;
Cmax: is considered to be dose-proportional within the range of 26–874 ng/mL;
Tmax: 1–2 days after administration;
Half-life: 116.7 h.		 Mainly excreted through urine and feces. Delayed gastric emptying. 129, 130, 131, 132, 133, 134, 135, 136