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Innovative Medicines & Omics Incretin mimetics in diabetes management

against sepsis-induced myocardial injury. In sepsis, the most common form of heart failure, with its onset and
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nitric oxide synthase overactivity leads to excessive nitric progression significantly influenced by obesity and T2DM.
oxide production, which, along with superoxide radicals, Patients with heart failure and preserved ejection fraction
forms peroxynitrite. Peroxynitrite interferes with cardiac (HFpEF)) are more likely to have T2DM individuals
function by modifying cardiac load, downregulating without heart failure, and this association is linked to
β-adrenergic receptors, impairing Type I calcium channel worse hemodynamic and clinical outcomes, such as higher
function, and reducing the efficiency of the mitochondrial symptom burden and reduced functional capacity. Few
electron transport chain complex in cardiac cells. effective treatment options exist for this population. 59
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Dulaglutide therapy drastically reduces nitric oxide Ozempic, a semaglutide-based GLP-1 RA, is indicated
production and nitric oxide synthase expression induced for T2DM management, with dosing that begins at
by LPS, indicating that dulaglutide may inhibit nitric oxide 0.25 mg weekly for 4 weeks, then increases to 0.5 mg,
synthase activation driven by inflammatory factors. 56 and may reach 1 mg if needed for glycemic control.

4.4. Semaglutide Administered subcutaneously, Ozempic enhances insulin
secretion, suppresses glucagon release, and slows gastric
Semaglutide (Figure 5) is an acylated GLP-1 analog with a emptying, helping manage post-meal blood glucose spikes.
modified amino acid structure. It is commonly marketed Its appetite-suppressing effects also contribute to weight
under various names and formulations: Ozempic and loss, making it particularly beneficial for overweight or
Wegovy as subcutaneous injections (at different doses obese individuals with diabetes. Studies indicate Ozempic
and strengths), and Rybelsus as an oral formulation. effectively lowers HbA1c, improves blood glucose control,
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Semaglutide is prescribed as an adjunct to diet and exercise and supports weight loss. 60
for glycemic control in individuals with T2DM. In addition,
it is indicated to reduce the risk of major cardiovascular Semaglutide, a GLP-1 RA, promotes glucose-dependent
events, such as non-fatal myocardial infarction and stroke, insulin release from pancreatic β-cells, inhibits excessive
glucagon secretion, and delays gastric emptying. As a weight
in patients with a history of cardiovascular disease and loss agent, it acts as a physiological regulator of appetite,
T2DM. No dose adjustment is necessary for patients with reducing caloric intake centrally. While it influences
renal failure or hepatic impairment when administering insulin secretion, delayed gastric emptying is thought to
semaglutide. 58
play a larger role in regulating postprandial hyperglycemia.
Wegovy is approved as a weight loss agent to be used Semaglutide has demonstrated excellent efficacy in
in conjunction with a reduced-calorie diet and increased reducing weight and lowering blood glucose levels. Unlike
physical activity in individuals with obesity (body mass conventional GLP-1 RAs, semaglutide directly affects
index [BMI] ≥30 kg/m ) or overweight (BMI ≥27 kg/m ) the brainstem, hypothalamus, and lateral septal nucleus,
2
2
with at least one weight-related comorbidities. It is also impacting central neurons, and thus promoting weight
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indicated for overweight or obese individuals with existing reduction. Semaglutide’s distinct anorexigenic mechanism
cardiovascular disease at an increased risk of major adverse may explain its superior weight reduction effects compared
cardiovascular events. The growing incidence of obesity to other GLP-1 RAs. This weight reduction effect appears to
has made heart failure with preserved ejection fraction be independent of common gastrointestinal adverse events,

Figure 4. Chemical structure of dulaglutide. Reproduced from Al Musaimi 12

Figure 5. Chemical structure of semaglutide
Notes: Black: peptide backbone; Red: 17-carboxyheptadecanoyl (C18 diacid); Pink: Glu; Blue: 8-amino-3,6-dioxaoctanoic acid (ADO). Reproduced from
Al Musaimi 12

Volume 2 Issue 1 (2025) 8 doi: 10.36922/imo.4911