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Innovative Medicines & Omics Incretin mimetics in diabetes management

which the dose can be increased to 5 mg once weekly. GLP-1. Following subcutaneous injection, lixisenatide is
Depending on individual patient needs and response, rapidly absorbed, reaching peak plasma concentration in
the dosage may be further increased up to a maximum of about 2 h, with a half-life of approximately 3 h. 85
15 mg once weekly. 82
The primary elimination pathway for lixisenatide
Zepbound is prescribed alongside a calorie-restricted is glomerular filtration. Cytochrome P450 isoenzymes
diet and increased physical activity to aid weight remain unaffected by lixisenatide. However, due to its
management in obese or overweight adults with at least effect on delaying gastric emptying, lixisenatide may
one weight-related comorbidity, such as hypertension, slow the absorption of orally administered medications,
dyslipidemia, T2DM, obstructive sleep apnea, or such as warfarin, ethinyl estradiol, and acetaminophen.
cardiovascular disease. Zepbound is administered Caution is advised when administering lixisenatide with
subcutaneously, starting at 2.5 mg once weekly and medications that have a narrow therapeutic range, such as
potentially increasing to a maximum of 15 mg once weekly warfarin, or with drugs that rely on precise dosing, such as
based on patient response and tolerance. The dual agonist antibiotics. For drugs that require timely absorption, it is
action on pancreatic β-cells promotes insulin production, recommended to administer them at least an hour before
while GIP activity enhances white adipose tissue function. lixisenatide. For oral contraceptives, the administration
In addition, signals of both receptor pathways in the brain should occur either 1 h before or 11 h after the lixisenatide
contribute to a stronger anorexigenic effect, supporting injection. 53
both glycemic control and weight reduction. The most
81
frequently reported side effects include gastrointestinal- Lixisenatide has a prolonged half-life due to its exendin-4
related events (nausea, diarrhea, and vomiting) and backbone and is administered once daily at an initial dose
decreased appetite. Some psychiatric adverse events have of 10 mcg via injection. After 2 weeks, the dose may be
83
also been noted. 84 increased to 20 mcg. Lixisenatide slows gastric emptying,
which significantly impacts postprandial glycemia. As
4.7. Lixisenatide monotherapy, it effectively reduces HbA1c, fasting glucose,
Lixisenatide (Figure 8), a GLP-1 RA, is commonly marketed and postprandial glycemia. In animal studies, lixisenatide
as Adlyxin. It is a peptide composed of 44 amino acids. administered peripherally has shown the ability to cross
Similar to exenatide, lixisenatide is derived from exendin-4 the blood-brain barrier. Its elimination is thought to occur
but includes six additional lysine residues at its C-terminus, through glomerular filtration, tubular reabsorption, and
replacing a proline residue. The C-terminal amino acid metabolic catabolism, although the composition of its
(position 44) is amidated. Approximately 55% of lixisenatide metabolites and their possible mechanisms of action remain
is bound to plasma proteins, and it binds to GLP-1 receptors unknown. Lixisenatide is linked to modest decreases in
with an affinity up to 4 times higher than that of human body weight, a considerable reduction in HbA1c (0.5–1%),

Figure 8. Chemical structure of lixisenatide
Notes: Blue: Differences from exenatide. Reproduced from Al Musaimi 12

Volume 2 Issue 1 (2025) 11 doi: 10.36922/imo.4911