How does semaglutide work?

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Semaglutide, the active ingredient in Wegovy, is a glucagon-like peptide-1 (GLP-1) receptor agonist that has been approved by the Food and Drug Administration (FDA) for weight loss in adults with overweight or obesity.

When combined with lifestyle changes like diet and exercise, semaglutide injections can help promote weight loss through several key mechanisms outlined below.

5 ways semaglutide promotes weight loss

1. Appetite regulation

Semaglutide mimics the natural hormone GLP-1, which is produced in the gut and plays a key role in regulating appetite and food intake. GLP-1 receptors are found in the brain, particularly in the hypothalamus and brainstem, which are involved in controlling hunger and satiety. By activating the GLP-1 receptors in the brain, semaglutide helps reduce feelings of hunger, leading to decreased calorie intake.

2. Delayed gastric emptying

Semaglutide slows down the rate at which food leaves the stomach and enters the small intestine, a process known as delayed gastric emptying. This delayed gastric emptying leads to a prolonged sense of fullness and satiety, further reducing food intake.

3. Glucose-dependent insulin secretion

Semaglutide enhances the secretion of insulin in a glucose-dependent manner, meaning it increases insulin release only when blood glucose levels are elevated. This helps to improve blood sugar levels and reduce the risk of hypoglycemia (low blood sugar).

4. Glucagon suppression

Glucagon is a hormone that is produced by the pancreas and plays a key role in regulating blood sugar levels by stimulating the liver to release glucose into the bloodstream. When semaglutide is administered, it works by binding to GLP-1 receptors in the pancreas, which leads to the suppression of the release of glucagon. By suppressing the release of glucagon, semaglutide helps to lower blood sugar levels in individuals with diabetes. By reducing glucagon levels, semaglutide further helps to maintain healthy blood sugar levels, which is particularly beneficial for individuals with type 2 diabetes.

5. Energy expenditure and lipid metabolism

Semaglutide has been shown to increase energy expenditure and promote fat burning, leading to reductions in body weight and improvements in body composition. It may also have a positive impact on lipid metabolism, contributing to favorable changes in cholesterol and triglyceride levels.

All of these above mechanisms make semaglutide a highly effective weight-loss medication when used as part of a comprehensive weight management program that includes a healthy diet and exercise. The sustained activation of the GLP-1 receptors by semaglutide is a key factor in its ability to achieve significant and sustained weight loss in individuals with overweight or obesity.

Already taking GLP-1s? Discover our companion to weight-loss medications from the experts at Mayo Clinic.

Who qualifies for semaglutide?

The criteria for individuals to qualify for semaglutide treatment can be summarized as follows:

For individuals with type 2 diabetes: (Ozempic)

• Have a body mass index (BMI) of 27 kg/m² or higher
• Have inadequate glycemic control (elevated blood sugar levels) despite the use of other diabetes medications

For individuals without diabetes (for weight loss): (Wegovy)

• Have a BMI of 30 kg/m² or higher (obesity)
• Have a BMI of 27 kg/m² or higher (overweight) and at least one weight-related condition, such as high blood pressure, high cholesterol, sleep apnea, or other obesity-related health conditions.

Semaglutide is generally not recommended for use in pregnant or breastfeeding women due to the limited data on its safety in these populations.

You should work closely with your healthcare provider to determine if you meet the criteria for semaglutide treatment. The provider will evaluate your medical history, current health status, and treatment goals to decide if semaglutide is the most appropriate medication.

It's also crucial to be aware of your insurance coverage and any potential out-of-pocket costs associated with semaglutide, as the level of coverage may vary.

Are there side effects?

While semaglutide is generally well-tolerated, like with all medications, it may come with some side effects, such as stomach pain, nausea, vomiting, and diarrhea.

More serious, less common side effects

On rare occasions, some weight-loss medications can cause symptoms including dizziness, light-headedness, shakiness or sweating. These symptoms may be due to the medication, they may be a symptom of dehydration, or they may result from a blood glucose level that’s too low (hypoglycemia). If you experience severe dizziness, shakiness or sweating, reach out immediately to your health care team.

Although uncommon, weight-loss medications also can cause other serious side effects, including an inflamed pancreas (pancreatitis), gallstones, kidney problems or allergic reactions.

These drugs also aren’t recommended if you have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia. Animal studies have linked these drugs with thyroid tumors. But until more long-term studies are done, the risk to humans isn't known. Therefore, you should work closely with your healthcare provider to carefully evaluate the risks and benefits for using semaglutide and monitor for any serious or long-term symptoms to ensure the safe and effective use of semaglutide.

Follow a comprehensive healthy lifestyle program

A healthy diet and physical activity, in conjunction with adequate sleep, social support, and stress management, will always be the bedrock of a healthy weight and overall good health. We've developed the Mayo Clinic Diet for Weight-Loss Medications as a companion lifestyle program to support you on your weight-loss journey. This program might be right for you if you are already taking weight-loss medications.

Using GLP-1s? The Mayo Clinic Diet now supports your journey with a special Companion program for weight-loss medication.