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Innovative Medicines & Omics Incretin mimetics in diabetes management

such as nausea and vomiting. In addition, semaglutide in approximately 3 – 5 days, with a metabolism similar to
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lowers LDL cholesterol but, like other GLP-1 Ras, does not human serum albumin in the vascular endothelium and a
increase high-density lipoprotein cholesterol levels. The half-life of up to 5 days. Its mechanism includes slowing
inhibition of cardiovascular events may be attributed to gastric emptying and increasing glucose-dependent insulin
improved lipid metabolism, increased insulin secretion, secretion. Compared to other GLP-1 RAs, albiglutide is
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and reductions in chronic systemic inflammation. associated with fewer episodes of nausea, likely due to its
Semaglutide has also shown promise in improving fatty substantial molecular structure that prevents crossing the
liver by reducing triglycerides and significantly enhancing blood-brain barrier. 76
liver function markers. It is metabolized through the Albiglutide is synthesized through recombinant DNA
proteolytic breakdown of the peptide framework, followed technology, comprising two tandem repeats of a fused
by β-oxidation of its fatty acid side chain, and is primarily 30-amino acid sequence. With only one amino acid
excreted through urine and feces. 64 alteration, the amino acid sequence of albiglutide closely
Rybelsus, an oral formulation of semaglutide, offers resembles endogenous human GLP-1, with this alteration
convenience in administration. It similarly delays gastric conferring resilience against DPP-4 degradation. The
emptying, aiding in the control of postprandial glucose fusion of two recombinant molecules with human serum
spikes. The starting dose is 3 mg daily for 30 days, albumin effectively prolongs the plasma half-life of
followed by an increase to 7 mg, with the option to go albiglutide. 77
up to 14 mg for additional glycemic control. Rybelsus Albiglutide may have cardioprotective effects by
also promotes weight loss by reducing appetite. Due to reducing endoplasmic reticulum stress, modulating
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nutrient-drug interactions, Rybelsus should be taken on an autophagy, and promoting anti-inflammatory pathways.
empty stomach, ideally on waking, with a small amount The indirect beneficial effects of GLP-1 RAs on the
of water, at least half an hour before any food, liquids, or ventricles largely stem from their positive impact
other oral prescriptions. While gastrointestinal adverse on inflammation, endothelial function, and glucose
effects are common with GLP-1 RAs, most individuals on uptake, as GLP-1 receptor expression in ventricular
oral semaglutide tolerate it well. Counseling on potential cardiomyocytes is relatively low. Furthermore, research
sensations of fullness or nausea can improve adherence, as suggests that GLP-1 RAs modulate extracellular matrix
nausea often subsides over time. 66 alterations, potentially attenuating cardiac remodeling

Recent publications indicate several new and, in post-myocardial infarction. In heart failure, characterized
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some cases, serious side effects of semaglutide, including by calcium overload, GLP-1 RA therapy may modulate
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hyperemesis gravidarum, psychiatric adverse events, cytosolic Ca levels by inhibiting phosphorylation of
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biliary disease, pancreatitis, appendicitis, bowel the ryanodine receptor 2 and blocking the activation of
obstruction, gastroparesis, and elevated liver enzymes. 75 calmodulin-dependent protein kinase II. Additionally,
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GLP-1 mimetics demonstrate antioxidative properties,
4.5. Albiglutide preventing the generation of intracellular and
Albiglutide (Figure 6), a complex polypeptide, acts as a mitochondrial ROS in methylglyoxal-treated cells. 78,79
GLP-1 RA and is commonly marketed under the trade Albiglutide is generally well tolerated, though rare
name Tanzeum. Available in 30 mg/pen and 50 mg/pen, it is adverse events such as pancreatitis and hypersensitivity
provided in a lyophilized state and requires reconstitution reactions may occur. To prevent DPP-4-mediated
before use. Albiglutide comprises two GLP-1 molecules degradation, a Gly8Ala mutation was introduced at the
fused with human serum albumin, and it is administered as cleavage site of the GLP-1 molecule. Albiglutide employs
a 30 mg subcutaneous injection once weekly. If the glycemic a unique approach: two DPP-4-resistant GLP-1 RA copies
response is insufficient, the dose can be increased to 50 mg are fused at the N-terminus, with the terminal arginine
weekly. Albiglutide reaches peak plasma concentrations linked to albumin to enhance stability. 80

Figure 6. Chemical structure of albiglutide. Reproduced from Al Musaimi 12

Volume 2 Issue 1 (2025) 9 doi: 10.36922/imo.4911