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Innovative Medicines & Omics Incretin mimetics in diabetes management

such as cardiovascular disease. In T2DM patients with improved glycemic control, as it lowers HbA1c, fasting
cardiovascular disease or at high risk, liraglutide treatment glucose, and postprandial glucose levels. In addition,
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lowers cardiovascular event risk. It is also approved for dulaglutide supports weight loss and improves pancreatic
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secondary prevention of cardiovascular disease. Beyond its β-cell function by promoting cellular regeneration, which
antidiabetic properties, liraglutide exhibits anti-apoptotic, increases β-cell mass and prevents apoptosis in various cell
anti-inflammatory, antioxidant, and neuroprotective types, including muscle, lung, and pancreatic β-cells. These
effects, potentially making it useful in treating neurological regenerative effects help slow the progression of T2DM
diseases. Notably, liraglutide can traverse the blood-brain and delay the need for insulin therapy. 50
barrier. Its anti-inflammatory effects after intracerebral Dulaglutide also provides cardioprotective benefits,
hemorrhage are mediated by GLP-1 amide, a metabolite including reductions in blood pressure and improvements
generated through DPP-4 cleavage of liraglutide. in lipid profiles, such as lowering LDL cholesterol. It has
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Liraglutide further aids insulin sensitivity by suppressing been shown to increase the number of endothelial cells and
endogenous glucose production and glucagon release, endothelial progenitor cells in peripheral blood, reduce
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while its effects on gastric emptying and appetite reduction persistent inflammation, enhance endothelial function, and
support weight management. ultimately boost arterial elasticity in patients with T2DM.
Victoza, a formulation of liraglutide for T2DM As a second-line therapy, dulaglutide is recommended in
management, is prescribed with an initial dose of addition to diet and exercise for patients who struggle to
0.6 mg once daily, titrating to 1.2 mg and up to 1.8 mg achieve glycemic control with metformin monotherapy.
as needed. It enhances blood glucose control through Dulaglutide has shown particular effectiveness in reducing
multiple mechanisms, including increasing insulin fasting plasma glucose compared to postprandial blood
secretion, reducing glucagon, slowing gastric emptying, glucose and acts through a glucose-dependent mechanism,
and promoting weight loss through appetite suppression. resulting in a minimal risk of severe hypoglycemia. Mild
Common side effects include nausea, vomiting, diarrhea, gastrointestinal adverse effects, such as nausea, vomiting,
and headaches, while more serious risks involve and diarrhea, may occur, typically worsening in the first
pancreatitis and kidney injury. Victoza is contraindicated 2 weeks but diminishing over time. No dose adjustments
in patients with a history of medullary thyroid carcinoma are required in patients with renal or hepatic impairment
or multiple endocrine neoplasia syndrome Type 2 due to when administering dulaglutide. 51,52
an increased risk of thyroid tumors. 48 Beyond its role as an antidiabetic agent, a 2023 study
In addition to its use in diabetes management, highlighted dulaglutide’s potential to protect against sepsis-
liraglutide is also available as Saxenda for long-term induced lung injury in mice. 53 Sep sis can trigger the excessive
weight management in patients with weight-related release of inflammatory mediators, including cytokines,
conditions. Approved as an adjunct to a reduced-calorie ROS, and reactive nitrogen species. Through the activation
diet and increased physical activity, Saxenda is indicated of cyclic adenosine monophosphate/protein kinase A
for individuals with conditions such as hypertension, and cyclic guanosine monophosphate/protein kinase G
dyslipidemia, or obesity. Common side effects include signaling pathways, these reactive nitrogen species and
headache, constipation, heartburn, malaise, and localized ROS can damage mitochondria, leading to mitochondrial
reactions at the injection site. Proper storage is essential: apoptosis. Sepsis-related cardiac damage is also linked to
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unused pens should be refrigerated at 4–8 °C and protected oxidative stress, primarily induced by elevated ROS levels.
from light and heat, and they should not be frozen. 49 Activation by lipopolysaccharides (LPS) markedly increases
oxidative stress in cardiac cells, as evidenced by heightened
4.3. Dulaglutide nitric oxide generation and reduced glutathione levels.
Dulaglutide (trade name Trulicity) is a long-acting GLP-1 Following dulaglutide treatment, markers of oxidative
RA with two modified GLP-1 analogs connected to an Fc stress are reduced, implying that dulaglutide may protect
fragment of human IgG4 (Figure 4). It is administered cardiac cells from LPS-induced oxidative stress injury.
subcutaneously once weekly, at any time of the day, with Two key markers of myocardial cell dysfunction, creatine
or without food. The initial dose is 1.5 mg, with an option kinase-myoglobin, and troponins, are frequently employed
to gradually increase to 3 mg as needed. Dulaglutide to evaluate acute myocardial infarction. LPS stimulation
has a half-life of 5 days, allowing for its weekly dosing. markedly increases creatine-kinase myoglobin expression
Patients using dulaglutide alongside insulin should avoid in myocardial cells, confirming that LPS is a primary
injecting it into the same area. It has demonstrated efficacy factor in myocardial dysfunction. Dulaglutide significantly
comparable to other GLP-1 RAs and is associated with decreased this dysfunction, suggesting a protective effect

Volume 2 Issue 1 (2025) 7 doi: 10.36922/imo.4911