Introduction
Ozempic, known generically as semaglutide is a Glucagon-like peptide-1 (GLP-1) agonist which is widely popular in managing type-2 diabetes and obesity. It mimics the action of the natural hormone GLP-1 which is released from the small intestine.1
GLP-1 mainly acts in three ways on glucose and these actions are mediated by the GLP-1 receptors.1
Ozempic, basically a GLP-1receptor agonist (GLP-1RA) activates the receptors expressed in pancreas, gastrointestinal tract, heart, lungs, kidneys, and brain to triggers GLP-1 hormonal activities.2
The actions on pancreas, gut and brain together maintain blood sugar level along with weight management that are evident with liraglutide and semaglutide.2,3
Mechanism of Action on Pancreas: This is responsible for maintaining blood glucose levels.
- Triggers insulin release from pancreatic beta cells to move the sugar from blood into the cells therefore lowering the blood glucose level.
- Blocks the secretion of glucagon from pancreatic alpha cells which is responsible for raising blood glucose levels by making the liver release glucose when necessary.4,5
Slowing Down Digestion in Gut:
Ozempic delays gastric emptying which reduces the rate of glucose release from food in bloodstream right after meals. It makes a person feel full for a longer period which leads to less intake of food over time. This effect helps both in blood sugar stability as well as weight management.3,4
Feeling of Satiety in Brain:
Ozempic acts on the hypothalamic area of the brain that processes hunger and satiety.1
GLP-1, along with Glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones. Incretin hormones are released from the upper (GIP) and lower (GLP-1) gut cells after food intake to stimulate insulin secretory response by two to four-fold. In cases of type 2 diabetes mellitus this incretin effect of GIP and GLP-1 are diminished, however the glucagonostatic effects of GLP-1 are preserved to the extent that stimulating the GLP-1 receptors significantly reduces plasma glucose and improves glycaemic control. Thus, it has become a parent compound of incretin-based glucose-lowering medications. In obese people GLP-1 secretion is impaired which might explain why the hunger pangs are constantly active in these people. GLP-1agonist reduces cardiovascular events in type 2 diabetics further to its effects in adipose cells and bones and is now plays a key role in endocrine and obesity-related therapies.6
Discovery and Development
Semaglutide was developed by Novo Nordisk as a next-generation GLP-1 receptor agonist, following the clinical success of earlier agents like exenatide and liraglutide.
The connection between pancreas, gut and incretin hormones were discovered by Bayliss and Starling in the early part of the twentieth century. GLP-1 accounts for 70% of postprandial insulin secretion. Ever since this discovery, GLP-1’s potential therapeutic importance on type 2 diabetes was studied. GLP-1 itself is 30 amino acid peptide hormone and has short half-life which limits its therapeutic use; thereby, various approaches were used until the albumin binding human GLP-1RAs liraglutide, and subsequently semaglutide were developed. All current GLP-1RAs are injectable.
Plasma albumin are the most abundant of plasma proteins. 10-15gm albumin is produced by the liver daily and it has half-life of several weeks which results in its stable concentration in the blood stream. Albumin binds to a variety of components in plasma which include many drugs and is responsible for solubility and transportations of substances like fatty acids and steroids. The fatty acids C10, C12, C14, C16, and C18 were found to bind to seven sites on albumin. The drug giant Novo Nordisk studied the concept of using fatty acids as albumin tags to prolong the duration of action of peptides and proteins. The fatty acid derivatization was employed to prepare GLP-1 analogs that could bind to albumin in a reversible manner and resist degradation by dipeptidyl peptidase-4 (DPP-4) for a prolonged half-life.
The entire GLP-1 sequence was conducted to derive the role of each 30 amino acids. The C-terminal of GLP-1 binds to the extracellular domain, whereas the N-terminal binds to the transmembrane domain of the GLP-1 receptors. This led to manufacturing a series of GLP-1 analogs with various fatty acids to investigate the effect of the attachment of fatty-acid side chains.2
Based on these studies and comprehensive characterization, liraglutide, a 97% homologous of human GLP-1 was discovered.7
The 16-carbon fatty acid chain of liraglutide causes noncovalent reversible binding to albumin, has high receptor potency, slows absorption from the injection site, and protects the molecule from DPP-4 breakdown. Liraglutide’s elimination half-life of 13 hours makes it a once daily dosing drug. With a dose of 1.2 and 1.8 mg/day given as monotherapy for up to 52 weeks has shown to reduce hemoglobin A1c (A1C) level from 0.6-1.6%; combination therapy of liraglutide with oral antidiabetic agents demonstrated mean A1C reductions up to 1.5%. The satiety effect of liraglutide was documented to generate weight loss of 3.38 kg in clinical trials, making it ideal for obese patients with type 2 diabetes mellitus.7
There is a theory that only the free fraction of the drug in the plasma that is not bound to albumin would be available to activate the GLP-1R. Therefore, the stronger the affinity to albumin the smaller the free and active circulating fraction of the GLP-1 peptide. The challenge with liraglutide was its strong affinity for albumin, which lead to diminished potency for the GLP-1R and shorter plasma half-life and the reason for its once daily injectable dose.
Semaglutide, on the other hand was designed to address the challenges of liraglutide, particularly its once daily dosing. The structure of GLP-1RAs and its activity are dependent on the length of fatty di-acid. After a systematic test of derivatives from C12 to C20 fatty acids, the C18 di-acid was used in semaglutide as it was concluded to be the optimal choice. The C18 di-acid (containing two carboxyl groups as opposed to one in fatty acids) together with a γGlu-2xOEG linker results in the highest albumin affinity combined with GLP-1R potency; it resisted DPP-4 degradation, extending its half-life to a week to achieve plasma levels sufficient to control blood glucose following a once weekly dosing.2
The U.S. FDA approved Ozempic in December 2017 for adults with T2DM.8In June 2021, semaglutide received approval under the name Wegovy at a higher dose (2.4 mg weekly) for chronic weight management in adults with obesity or overweight conditions.9
Novo Nordisk has not granted patent rights for semaglutide/Ozempic to any other company for the US market or outside the US market. They have the patency right till 2032 in the US and have claimed to be the only approved manufacturer of semaglutide globally. However, countries like Bangladesh and Laos, classified as least developed nations by the United Nations, enjoy exemptions from industry patent rules and may have access to generic semaglutide despite Novo Nordisk’s international patency rights. On that note, Novo Nordisk also pronounced that they cannot attest to the safety and effectiveness of products claiming to contain semaglutide made by other manufacturers.10
Indications for Use
FDA-Approved Indications (Ozempic):
- Type 2 Diabetes Mellitus & Weight Loss – as an adjunct to diet and exercise to improve glycemic control, and improved A1C.
- Cardiovascular Risk Reduction – in adults with T2DM and established cardiovascular disease to reduce the risk of major adverse cardiovascular events (CV death, nonfatal MI, or nonfatal stroke).
- Reduces Risk of Chronic Kidney Disease Progression- For adults with T2D and CKD, to reduce the risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death.11
Off-Label Use:
- Weight loss in individuals without diabetes, although the 2.4 mg version (Wegovy) is preferred due to official approval.12
How Ozempic Aids in Weight Loss
Weight reduction is one of semaglutide’s most striking effects, even in people without diabetes. Clinical trials demonstrate substantial body weight loss through reduced caloric intake, not increased energy expenditure.
In a double-blind trial, 1961 non-diabetic adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 were randomly assigned in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The mean change in body weight from baseline to week 68 was −14.9% in the semaglutide group as compared with −2.4% with placebo group.13
In another study, 408 people in the US were given weekly semaglutide injections. Over the first three months, those included in the final analysis (175 people) lost an average of 6.7kg. Over the first six months, they lost an average of 12.3kg.14
A Mayo Clinic study of 297 patients showed that “the effectiveness of semaglutide in promoting weight loss varies significantly with a patient’s level of diabetes severity — provides valuable insights for clinical practice. Our data suggest that patients with less severe diabetes may experience more substantial weight-loss benefits from semaglutide.” 15
The actual drug that is approved for weight loss is Wegovy, also semaglutide. Ozempic is not approved for weight loss.Ozempic has a smaller dose of semaglutide than Wegovy.16
The once weekly dose of Ozempic may cause withdrawal after it is stopped. Within a week after stopping the medicine, the hunger pangs and cravings may return since one may not feel full for as long as they felt while they were on the drug. People with type 2 diabetes may experience high blood sugar levels.16
Side Effects
Common Side Effects:
- Nausea, vomiting, diarrhea, constipation, and stomach pain are the common side effects.
- It is advisable to eat bland, low-fat foods (crackers, rice, toast), food that contain water (soup, gelatin), avoid fried and greasy food, avoid sweets, and avoid lying down after eating.17
Serious Risks:
- Thyroid C-cell tumors: Contraindicated in individuals with personal/family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 syndrome. Studies on rodents showed Ozempic causing thyroid tumors, including thyroid cancer. It is not confirmed in humans.
- Pancreatitis: Risk is rare but notable.
- Cholelithiasis: Increased risk due to rapid weight loss.
- Allergic Reaction: Stop Ozempic is there is swelling of face, lips, tongue, throat, severe rash or itching, fainting or feeling dizzy, or rapid heartbeat.
- Patients on Ozempic: Must inform physicians that they are on Ozempic before any surgery since Ozempic might increase the change of food or liquid getting into the lungs during surgery or other procedures.17
- Hypoglycemia- When used with sulfonylurea or insulin, it may cause hypoglycemia. Must check blood sugar regularly if there are change in diet, exercise and additional diabetic medicines.18
- Ozempic intake must be monitored under a physician.
Safety in Special Populations
| Population | Safety Concern |
| Pregnancy | Contraindicated; discontinue at least 2 months before planned pregnancy. |
| Breastfeeding | Insufficient data; caution advised. |
| Renal/Hepatic Impairment | No dose adjustment required in mild/moderate dysfunction; monitor symptoms.18 |
Drug Interactions
- If a dose of Ozempic is missed, then it must be taken as soon as possible (within 5 days). But if more than 5 days have passed then skip the missed dose and take the next dose as per schedule.18
| Drug group or drug name | Drug examples | What can happen |
| insulin | • insulin lispro (Humalog) • insulin degludec (Tresiba) • insulin glargine (Lantus, Basaglar) | can increase the risk of side effects from Ozempic and insulin |
| sulfonylureas, a kind of diabetes medication | • glimepiride • glyburide (DiaBeta) • glipizide (Glucotrol XL) | can increase the risk of side effects from sulfonylureas and Ozempic |
| antimalarial drugs | • hydroxychloroquine (Plaquenil) • chloroquine | can increase the risk of side effects from Ozempic |
| oral medications | • warfarin (Jantoven) • digoxin (Lanoxin) • sitagliptin (Januvia) • many others | can make oral medications less effective than usual |
| certain antibiotic drugs | • amoxicillin • clarithromycin | can increase the risk of side effects from Ozempic |
19
Conclusion
Ozempic (semaglutide) has changed the paradigm of diabetes and obesity management. It not only improves glycemic control but also promotes weight loss and reduces cardiovascular events. Clinicians must be aware of its contraindications and manage side effects appropriately to optimize its clinical benefits.
Author of this article
Dr. Maliha Mannan Ahmed, MBBS (BMC), MBA (ULAB), Masters in Healthcare Leadership (Brown University, USA) and Level 1 Certification on Precision Nutrition. The Executive Editor of The Coronal.
References
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3. The Mechanism Behind Ozempic: How It Aids in Weight Loss | Spa Black. August 1, 2024. Accessed July 17, 2025. https://spablack.com/how-does-ozempic-work-for-weight-loss/
4. GLP-1 RA Mechanism of Action | Ozempic® (semaglutide) injection 0.5 mg, 1 mg, or 2 mg. Accessed July 17, 2025. https://www.novomedlink.com/diabetes/products/treatments/ozempic/about/mechanism-of-action.html
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8. Ozempic (semaglutide) FDA Approval History. Drugs.com. Accessed July 17, 2025. https://www.drugs.com/history/ozempic.html
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10. Silver A. How Asian pharma suppliers cash in on Ozempic copies. Reuters. https://www.reuters.com/business/healthcare-pharmaceuticals/how-asian-pharma-suppliers-cash-ozempic-copies-2024-11-01/. November 1, 2024. Accessed July 17, 2025.
11. Ozempic® (semaglutide) injection 0.5 mg, 1 mg, or 2 mg | Official HCP Site. Accessed July 17, 2025. https://www.novomedlink.com/diabetes/products/treatments/ozempic.html
12. Semaglutide, also known as Ozempic, for weight loss – what you need to know | UCLA Health. Accessed July 17, 2025. https://www.uclahealth.org/news/article/semaglutide-weight-loss-what-you-need-know
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14. Considering taking a weight-loss drug like Ozempic? Here are some potential risks and benefits. 1712121300. Accessed July 17, 2025. https://public-health.uq.edu.au/article/2024/04/considering-taking-weight-loss-drug-ozempic-here-are-some-potential-risks-and-benefits
15. Association between individualized metabolic surgery scores and weight-loss outcomes in patients treated with semaglutide – Mayo Clinic. Accessed July 17, 2025. https://www.mayoclinic.org/medical-professionals/digestive-diseases/news/association-between-individualized-metabolic-surgery-scores-and-weight-loss-outcomes-in-patients-treated-with-semaglutide/mac-20569221
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19. Ozempic Interactions: Other Medications, Alcohol, and More. Accessed July 17, 2025. https://www.healthline.com/health/drugs/ozempic-interactions