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Innovative Medicines & Omics Pharmacotherapy of obesity

nervous system. Its main function is to stimulate insulin pancreatitis or severe gastrointestinal issues, as well as
secretion in response to increased blood glucose levels. during pregnancy and breastfeeding.
Besides, GLP-1 stimulates the growth and replication
of pancreatic β-cells and reduces their apoptosis. The 11.9. Metformin
mechanism of action of GLP-1 is through the binding of Recent research indicates that the weight loss associated
the peptide to its receptor, a G protein-coupled receptor with metformin may result from its effects on hypothalamic
that activates multiple important intracellular pathways. appetite regulation, changes in the gut microbiome,
One pathway includes adenylate cyclase, resulting in and the reversal of aging-related effects. In addition,
an intracellular increase in levels of cyclic AMP. The metformin is being investigated for its potential in treating
intracellular increase in cyclic AMP activates protein kinase obesity-related complications, including hepatic steatosis,
A, which enhances the exocytosis of insulin-containing obstructive sleep apnea, and osteoarthritis. 78
vesicles from pancreatic β-cells, thus enhancing glucose- Metformin is administered orally in three different
induced insulin secretion. GLP-1 also inhibits the release release rates: immediate release-IR , sustained release-SR /
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of glucagon from pancreatic α-cells, which decreases tablets, and extended Release-ER /tablets. For adults, the
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glucose production by the liver.
IR tablets are administered 500 mg twice daily or 850 mg
11.8. Tirzepatide once daily with meals, with an increase of 500 mg weekly or
850 mg every two weeks based on tolerance. The maximum
Tirzepatide is a gastric inhibitory polypeptide analog and dose is 2,550 mg/day (divided into 2 – 3 doses). The ER
GLP-1 receptor agonist. It works by activating the GLP-1 tablets for adults are administered in 500 mg or 1,000 mg
receptors in the brain’s hypothalamus, which controls daily with dinner, with a dosage increase by 500 mg weekly.
appetite. GLP-1 receptor agonists reduce hunger and The maximum dose is 2,000 mg/day. For adults, the SR
cause the patient to eat less by activating these receptors. tablets are given 500 mg once daily with dinner and then
To reduce appetite and promote fullness, GLP-1 receptor increased by 500 mg weekly based on tolerance, with a
agonists also attach to the GLP-1 receptors on specific maximum dose of 2,000 mg/day (some guidelines allow
brain neurons. It has been demonstrated that they cause up to 2,500 mg in divided doses). On the other hand for
79
the sensation of fullness by delaying the emptying of the children, metformin SR/ER starting dose is 500 mg once
stomach during the 1 h after eating. GLP-1 receptor daily with dinner and then increase by 500 mg weekly based
st
agonist users report feeling less hungry and arousing, on tolerance with maximum dose being 2,000 mg/day (in
preferring fewer high-calorie foods, experiencing less food one or two doses). The starting dose of IR metformin for
cravings, and having greater overall control over their children is 500 mg twice daily with the maximum dose of
eating patterns. 76 2,000 mg/day (divided into 2 – 3 doses).
Tirzepatide (Mounjaro) comes as a pre-filled pen for Metformin is generally well-tolerated, but it can
subcutaneous injection. After four weeks, the starting cause some side effects, particularly in the digestive
dose is increased to 5 mg from the initial 2.5 mg once each system. Common side effects include nausea, diarrhea,
week. Depending on response and tolerance, doses may be abdominal discomfort, and bloating, especially when
increased to 7.5 mg, 10 mg, 12.5 mg, or 15 mg/week. starting treatment. Long-term use may lead to a vitamin
Headache, nausea, vomiting, diarrhea, constipation, B12 deficiency. In rare cases, metformin can cause
and abdominal pain are typical Mounjaro’s side effects. lactic acidosis, a serious condition that leads to muscle
Fatigue, decreased appetite, and dizziness are possible pain, difficulty breathing, and confusion, especially in
additional adverse effects. Rarely, this medicine results in individuals with kidney or liver problems. It can also cause
severe adverse effects such as kidney issues, gallbladder a metallic taste in the mouth. These side effects are usually
illness, and pancreatitis. Hypoglycemia, or low blood sugar, manageable with dose adjustments or by taking metformin
can also occur in patients using Mounjaro. Hypoglycemia with food. 80
can cause dizziness, perspiration, shakiness, and confusion. Another research conducted a 6-month study on 154
Furthermore, thyroid hormone levels may fluctuate as consecutive outpatients with a BMI ≥27 kg/m², treating
a result of Mounjaro. Last but not least, Mounjaro could them with metformin up to 2,500 mg/day, while 45
alter cholesterol levels. While using this drug, patients’ untreated patients served as controls. Weight changes were
cholesterol levels should be routinely monitored. 77
monitored, and before starting treatment, insulin sensitivity
Patients with MEN 2 or personal or family history was assessed using the homeostasis model assessment and
of medullary thyroid cancer should not use Mounjaro. Matsuda indices after a 75 g oral glucose tolerance test.
It is also contraindicated in individuals with a history of Results showed that the metformin group lost an average

Volume 2 Issue 2 (2025) 12 doi: 10.36922/imo.8316