Semaglutide is a pharmaceutical agent developed as an antidiabetic therapy to control blood glucose levels in individuals with type 2 diabetes mellitus. It functions as a glucagon-like peptide-1 (GLP-1) receptor agonist, enhancing insulin secretion and suppressing glucagon production, thereby aiding in the maintenance of glycaemic balance. Beyond its primary use in diabetes management, clinical trials have demonstrated its significant efficacy in promoting weight loss, even among non-diabetic obese individuals. These findings have sparked further research into its potential application as a pharmacological therapy for broader weight management.
Due to its dual benefits in glycaemic control and weight reduction, Semaglutide is increasingly adopted as a therapeutic solution for obesity management and healthy weight regulation.
Mechanism of Action
Semaglutide is an innovative GLP-1 receptor agonist that mimics the natural hormone responsible for regulating blood glucose levels and appetite. It stimulates insulin secretion, inhibits glucagon release, delays gastric emptying, and acts on brain centres to reduce hunger. These combined mechanisms make it effective in managing type 2 diabetes and facilitating substantial weight loss.
Key Benefits of Semaglutide
- Blood Glucose Regulation
Semaglutide triggers insulin secretion in response to elevated blood glucose levels, aiding type 2 diabetes patients in avoiding dangerous glycaemic spikes. - Appetite Suppression
By acting on the brain’s satiety centres, Semaglutide prolongs the sensation of fullness, thereby naturally reducing calorie intake. - Weight Reduction
By slowing gastric emptying and reducing portion sizes, Semaglutide supports obese individuals in achieving healthier body weight. - Cardiovascular Risk Reduction
Studies suggest that Semaglutide use can lower the risk of heart disease and stroke, particularly in type 2 diabetes patients with cardiovascular risk factors. - Overall Metabolic Health Improvement
In addition to glycaemic and weight control, Semaglutide contributes to better cholesterol and triglyceride profiles.
Efficacy in Obese Non-Diabetic Individuals
Semaglutide has also demonstrated substantial weight loss effects in non-diabetic obese populations. By reducing appetite and energy intake, it offers a sustainable weight management solution.
The Wilding et al. Study
A randomised clinical trial by Wilding et al. enrolled 1,961 obese participants (BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities) without diabetes, all of whom underwent lifestyle interventions. Participants were divided into two groups: one received 2.4 mg of subcutaneous Semaglutide weekly, and the other received a placebo.
Results after 68 weeks:
- Average weight loss was 14.9% in the Semaglutide group versus 2.4% in the placebo group.
- Mean body weight reduction: 15.3 kg with Semaglutide vs. 2.6 kg with placebo.
- 86.4% of the Semaglutide group lost ≥5% body weight vs. 31.5% in the placebo group.
- 50.5% of Semaglutide users lost ≥15% of their body weight compared to 4.9% in the placebo group.
- Participants on Semaglutide showed superior improvements in cardiometabolic parameters and physical functioning.
Dosage and Administration
Dosage must be individualised and prescribed by a healthcare professional. Treatment typically begins with a low dose to minimise side effects, gradually increasing to the therapeutic dose.
- Initial Dose:
- For type 2 diabetes: 0.25 mg weekly for the first 4 weeks
- For weight loss: 0.25 mg to 0.5 mg weekly, based on patient response
- Maintenance/Optimal Dose:
- For diabetes: 1 mg to 2 mg per week
- For weight management: Up to 2.4 mg per week
- Administration:
Semaglutide is administered subcutaneously once weekly in the abdomen, thigh, or upper arm. It should be injected on the same day each week for optimal efficacy.
Safety Profile and Side Effects
Most side effects are mild to moderate and gastrointestinal in nature, such as nausea or diarrhoea. Only 4.5% of Semaglutide users discontinued due to side effects, compared to 0.8% in the placebo group.
Common side effects include:
- Nausea and vomiting
- Diarrhoea or constipation
- Abdominal discomfort
- Headache
- Dizziness
- Injection site reactions (redness, swelling, irritation)
Serious but rare side effects:
- Acute pancreatitis
- Renal impairment
- Thyroid hormone level changes
These effects are generally transient. Seek immediate medical attention in case of severe symptoms such as pancreatitis, visual disturbances, or allergic reactions.
Contraindications: Who Should Avoid Semaglutide?
Semaglutide is not recommended for individuals with the following conditions, unless specifically advised by a physician:
- Personal or family history of medullary thyroid carcinoma
- History of acute pancreatitis
- Severe hepatic or renal impairment
- Pregnant or lactating women
- Individuals with severe gastrointestinal disorders like gastroparesis
Frequently Asked Questions (FAQs)
- Is Semaglutide safe for long-term use?
Yes, long-term safety has been supported by clinical trials. However, it should always be used under medical supervision to monitor for adverse effects and maintain appropriate dosing. - Can Semaglutide be used alongside other medications?
Yes, but only under the guidance of a healthcare provider. Dose adjustments of other antidiabetic drugs may be necessary to prevent hypoglycaemia or drug interactions.