The search for effective and safe weight loss treatments has led to the rise of semaglutide, a medication initially used for diabetes management. Semaglutide, particularly under the brand name Wegovy, has gained attention as a promising tool for chronic weight management in adults who are obese or overweight.
What is Semaglutide?
Semaglutide belongs to a class of medications known as glucagon-like peptide-1 receptor agonists (GLP-1 RAs). It mimics the GLP-1 hormone, which is released in the gut in response to eating. This hormone plays several roles in the body, including stimulating insulin production, reducing glucagon levels, and slowing down gastric emptying.
How Semaglutide Works
Semaglutide works by stimulating a receptor that increases insulin production and lowers glucagon levels (a hormone that raises blood sugar). It also slows down how quickly the stomach empties. In higher amounts, GLP-1 interacts with the parts of the brain that suppress appetite and signal fullness.
Semaglutide for Weight Loss
Currently, semaglutide is approved for weight loss under the brand name Wegovy. The typical dose for weight loss is 2.4 milligrams, administered weekly as subcutaneous (under the skin) self-injections.
Off-Label Use of Semaglutide
As interest in semaglutide for weight loss continues to grow, healthcare professionals are finding ways to manage the demand. Many prescribe other brands of semaglutide, such as Ozempic and Rybelsus, off-label (using a drug that is FDA-approved for a different reason). Many people use semaglutide off-label to help manage weight. The demand has become so high, that now there is a shortage for people who need this medication to help manage their diabetes.
Read also: Transformations with Ozempic
Efficacy of Semaglutide for Weight Loss
Research has consistently demonstrated the effectiveness of semaglutide injections for weight loss.
Clinical Trial Results
- Nondiabetic Patients: An RCT of nondiabetic patients (N = 1961) showed that after 68 weeks, the mean weight loss was 15% (15 kg) versus 2% (3 kg) with placebo (PC). The proportion of those who lost weight (≥ 5%) was 86% versus 32% (PC), with a number needed to treat (NNT) = 2, while the proportion who lost more weight (≥ 10%) was 69% versus 12% (PC), NNT = 2.
- Diabetic Patients: A dose-finding RCT3 of diabetic patients (N = 1210) given either 2.4 mg of SGT weekly, 1.0 mg of SGT weekly, or PC, found that after 68 weeks, mean weight loss was 10% (2.4 mg), 7% (1.0 mg), and 3% (PC). The proportion who lost weight (≥ 5%) was 69% (2.4 mg) versus 57% (1.0 mg) versus 29% (PC).
- Weight-Maintenance: A weight-maintenance RCT (N = 803) found that nondiabetic participants given 2.4 mg of SGT weekly for 20 weeks and then randomized to either continued SGT or PC.
Semaglutide vs. Liraglutide
In an SGT-sponsored RCT, high-dose SGT (0.4 mg/day) was superior to liraglutide (3 mg/day). Weight loss was 14% (17 kg) SGT versus 8% (8 kg) liraglutide. Besides weight loss, SGT increased quality of life for 40% to 50% of participants compared with about 30% taking PC.
Semaglutide Plus Lifestyle Changes
Used with lifestyle changes, 2.4 mg of subcutaneous SGT weekly resulted in a mean 10% to 15% weight loss (10 to 15 kg) over 68 weeks versus 2% to 3% (3 to 4 kg) with placebo (PC). Most (70% to 80%) lost 5% or more of their body weight.
Regaining Weight After Stopping Semaglutide
Studies have revealed that participants tend to regain the weight lost when they stop taking semaglutide. The fundamentals of obesity management will always be changes to diet and exercise. But having anti-obesity medications is another tool in the toolbox - depending on the person’s clinical history.
Side Effects of Semaglutide
The side effects of semaglutide are typically mild compared to the complications associated with overweight and obesity.
Read also: Comprehensive guide: Tirzepatide and Semaglutide for weight management
Common Side Effects
People taking semaglutide for weight loss may experience:
- Dizziness
- Fatigue
- Gastrointestinal issues, such as diarrhea, constipation, and gassiness
- Headache
- Stomach issues, including nausea, vomiting, pain, or distension (bloat)
Gastrointestinal issues are the most common complaint among people just starting semaglutide. These side effects may be reduced by beginning on a lower dose and then slowly increasing the amount taken.
Serious Side Effects
Stop taking Wegovy® and get medical help right away if you get a lump or swelling in your neck or an allergic reaction, serious side effects may happen, including pancreatitis. Gallbladder or severe stomach problems may occur. Call your provider if you have symptoms such as stomach pain, fever, yellowing of the skin or eyes, or clay-colored stools. In those with diabetes, taking Wegovy® with insulin or a sulfonylurea can increase the risk of low blood sugar. This can be a serious side effect. Wegovy® may increase the chance of food or liquid getting into your lungs during surgery, or other procedures that use anesthesia or deep sleepiness. Common side effects include nausea, diarrhea, vomiting, constipation, stomach pain, headache, tiredness, upset stomach, dizziness, feeling bloated, belching, low blood sugar in people with type 2 diabetes, gas, stomach flu, and heartburn. Some side effects may lead to dehydration, which may worsen kidney problems.
Adverse Effects
- Gastrointestinal adverse effects (AEs): 74% versus 48% (PC), number needed to harm (NNH) = 3.
Who Should Take Semaglutide?
The FDA recommends Wegovy for weight loss if you meet one of the following criteria:
- Have a body mass index (BMI) of 27kg/m2 or greater and at least one weight-related condition, such as high blood pressure, Type 2 diabetes, or high cholesterol
- Have a BMI of 30kg/m2 or greater
Who Should Avoid Semaglutide?
Avoid semaglutide if you have:
Read also: Semaglutide Without Diet Changes
- History of medullary thyroid cancer
- History of gallbladder disease
- History of pancreatitis
- Multiple endocrine neoplasia syndrome type 2 (MEN2)
Other glucagon-like peptide 1 agonists and SGT should likely be avoided in patients with a history of medullary thyroid carcinoma, pancreatitis, or tachyarrhythmias.
Consulting a Healthcare Provider
If you’re considering semaglutide for weight loss, your first step should be consulting your primary care physician (PCP). They know your personal and family medical history and can guide you in the best treatment for your condition. Semaglutide should be prescribed by a healthcare provider who can evaluate your specific health needs and medical history. Self-injecting without medical supervision can also increase the risk of infection, incorrect dosing and the possibility of severe allergic reactions.
Dosing and Administration
Semaglutide is usually started at 0.25 mg weekly and is increased by 0.25 mg every 4 weeks until the target dose is reached (as tolerated). Nausea and gastrointestinal upset are reported AEs, particularly during dose escalation. Adherence to weekly subcutaneous injections may be better than for daily injections.
Concerns with Compounded Versions of Semaglutide
Compounded drugs should only be used in patients whose medical needs cannot be met by an FDA-approved drug. Patients should obtain a prescription from their doctor and fill the prescription at a state-licensed pharmacy.
Risks of Compounded Semaglutide
Concerns with compounded versions of these drugs include:
- Improper storage during shipping may lead to quality issues.
- Counterfeit drugs may contain the wrong ingredients or harmful ingredients.
- Dosing errors can occur.
- Salt forms should not be used to compound semaglutide.
FDA Recommendations for Consumers
The agency encourages patients to be vigilant and know the source of their medicine. Carefully check labels of compounded GLP-1 drugs for warning signs such as spelling errors or incorrect addresses and ensure your medicine is provided by a licensed pharmacy and prescribed by a licensed health care provider. If you receive a product with a licensed pharmacy name on the label that you think might be fraudulent, contact the pharmacy to ask if it is their product. Talk to your doctor if you have questions about your medicines.
Important Considerations
- It is very important that your doctor check your progress at regular visits.
- Tell your doctor if you are pregnant or planning to become pregnant.
- Discuss alcohol consumption with your health care team.
- Do not take other medicines during the time you are using semaglutide unless they have been discussed with your doctor.
- Make sure you stay hydrated while taking this medication.
- If you are going to need surgery or a procedure, tell your care team that you are taking this medication.
Potential Benefits
Besides weight loss, SGT increased quality of life for 40% to 50% of participants compared with about 30% taking PC. In addition to weight loss, semaglutide can lead to a reduced risk of cancer, diabetes, and heart disease in people who are obese or overweight.
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