Semaglutide is a drug primarily prescribed by healthcare providers to treat type 2 diabetes. It is also remarkably effective in helping patients lose weight when used with a healthy diet and exercise. Semaglutide is on everybody’s lips these days, as it is the active ingredient in popular brand-name drugs like Ozempic, Wegovy, and Rybelsus. But what is semaglutide? And does it really work for weight loss?

This article will detail the various uses of semaglutide, how it works, its common side effects, and who it may be suitable for.

What is semaglutide?

Semaglutide is the active ingredient in several diabetes and weight loss drugs like Ozempic, Wegoby, and Rybelsus. This compound is a synthetic form of the naturally occurring hormone called glucagon-like peptide-1 (GLP-1).

Developed by Novo Nordisk, semaglutide was initially approved by the U.S. Food and Drug Administration (FDA) in 2017 as a part of the approval process for Ozempic, an injectable medication used to treat type 2 diabetes in adults.

In 2019, a new form of semaglutide was FDA-approved under the brand name Rybelsus. Rybelsus was the first-ever oral GLP-1 receptor agonist in American markets for treating type 2 diabetes.

Most recently, in 2021, the FDA approved a more potent dose of injectable semaglutide, this time under the brand name Wegovy. Unlike the other two forms of semaglutide, which cause weight loss but aren’t explicitly FDA-approved weight loss aids, Wegovy is specifically indicated to help individuals with obesity or overweight individuals with weight-related health problems lose weight. It is prescribed in conjunction with a healthy diet and regular exercise.

Because of rising type 2 diabetes and obesity rates around the globe, semaglutide use is skyrocketing. Semaglutide prescriptions have gone up fortyfold in the last five years. About 1.6% of the US population takes a form of semaglutide medication. However, according to some studies, over 53% of the US population would be considered eligible for a semaglutide prescription.

Semaglutide’s multiple benefits can help lower blood sugar, reduce body weight, and lower the risk of cardiovascular events—like heart attack, stroke, or heart disease—in millions of patients.

How does semaglutide work?

Semaglutide is a synthetic compound that imitates the effect of the natural hormone GLP-1 in the body. Semaglutide is officially classified as a glucagon-like peptide-1 receptor agonist, and its impact on blood sugar metabolism and calorie intake is multiple.

After eating a meal, your intestines release a hormone called GLP-1, which signals your pancreas to release more insulin. Insulin is a hormone that plays a crucial role in reducing blood sugar levels by facilitating the entry of glucose (sugar) into cells, where it can be used for energy or stored for later use. GLP-1 is especially important in ensuring that insulin is released at the right times, particularly after meals when blood sugar levels typically rise.

In addition to its role in insulin regulation, GLP-1 also has the added benefit of reducing the secretion of another hormone, glucagon, produced by the pancreas. Unlike insulin, glucagon has the opposite effect, increasing blood sugar levels by instructing the liver to release stored glucose into the bloodstream. By inhibiting glucagon, GLP-1 prevents the excessive release of glucose from the liver, thus keeping blood sugar levels from becoming excessively high.

GLP-1 also has an impact on the rate at which your stomach empties. When the pancreas releases GLP-1, it helps control the pace at which food moves from the stomach to the small intestine. This action can slow down the absorption of nutrients, including glucose (sugar), from the digestive tract into the bloodstream. Consequently, this prevents rapid spikes in blood sugar levels after meals. Additionally, slower stomach emptying can create a feeling of fullness, reducing overall food intake and contributing to weight management.

How does semaglutide cause weight loss?

It should be noted that higher doses of semaglutide are more likely to cause significant weight loss than the lower doses that are administered via Rybelsus or Ozempic. In addition, semaglutide is most effective as a chronic weight management aid when combined with lifestyle changes like a reduced-calorie diet and regular exercise.

When taken correctly, semaglutide can affect weight loss through two primary actions: blood sugar management and appetite regulation.

Semaglutide stimulates the pancreas to release insulin. This hormone is crucial in transporting glucose (sugar) from the bloodstream into cells, where it can be utilized for energy. By facilitating this process, semaglutide helps maintain stable blood sugar levels, reducing the likelihood of sudden energy fluctuations that can trigger cravings for high-calorie foods.

Furthermore, semaglutide effectively inhibits the production of glucagon, another hormone responsible for elevating blood sugar levels. Glucagon prompts the liver to release stored glucose into the bloodstream, but semaglutide intervenes in this process. By controlling glucagon, semaglutide helps keep blood sugar levels steady, mitigating the hunger pangs often caused by low blood sugar.

Semaglutide also influences appetite by interacting with GLP-1 receptors in the brain, particularly in the hypothalamus. When semaglutide binds to these receptors, it signals the brain to reduce appetite and curb cravings. This means that individuals taking semaglutide tend to experience reduced hunger and greater satisfaction from smaller meals.

Additionally, semaglutide slows down the rate at which the stomach empties its contents into the small intestine. This delay in stomach emptying leads to prolonged feelings of fullness after eating, ultimately reducing the inclination to consume more food.

It's important to note that semaglutide is typically prescribed with lifestyle modifications such as calorie reduction and increased physical activity. It is not intended to be the sole treatment for obesity but rather a supportive component of a comprehensive approach to weight management.

Is semaglutide effective for weight loss?

From October 5, 2018, to February 1, 2019, a study was conducted with 304 participants. They were randomly assigned to receive either semaglutide (152 participants) or a placebo (152 participants). This study looked at their body weight and various health parameters. Most of the participants were female (77.6%) and white (93.1%), with an average age of 47.3 years, an average weight of 106.0 kg, and an average body mass index—BMI—of 38.5 kg/m².

The study used two different approaches to analyze the effectiveness of semaglutide. The first approach, the 'treatment policy' estimand, looked at how semaglutide worked for all participants throughout the study, regardless of whether they stopped taking the medication or received other weight loss treatments. The second approach, the 'trial product' estimand, focused on how semaglutide worked when participants took it as intended.

Based on the 'treatment policy' estimand, semaglutide significantly reduced body weight compared to the placebo after 104 weeks. Participants taking semaglutide lost an average of 15.2% of their initial body weight, while those on the placebo only lost 2.6%. Semaglutide users were also more likely to achieve a weight loss of at least 5%. The study concluded that semaglutide was effective in helping participants lose weight.

Semaglutide also positively affected waist circumference, blood pressure, blood sugar levels, and other health markers. For example, it improved both systolic and diastolic blood pressure. It also positively affects glycated hemoglobin, fasting plasma glucose, and lipid profiles. These effects can reduce the risk of cardiovascular disease or events like heart attack or stroke.

In participants with prediabetes at the beginning of the study, semaglutide helped a significant number of them revert to normal blood sugar levels. Conversely, in participants with normal blood sugar at the start, very few developed prediabetes. None of the participants on semaglutide developed type 2 diabetes during the study.

In summary, the study found that semaglutide was effective in helping participants lose weight and improving various health parameters, making it a promising treatment for obesity and related health conditions.

Does semaglutide cause side effects?

Semaglutide has undergone numerous clinical trials to determine its safety and efficacy in treating type 2 diabetes and obesity. The FDA has approved three versions of semaglutide, indicating that it is safe for many patients requiring treatment for one or both conditions.

The most common side effects of semaglutide use are gastrointestinal issues. These include nausea, vomiting, diarrhea, constipation, gas, and heartburn. These side effects are usually mild.

While instances are rare, semaglutide may cause more serious side effects in some patients. These include:

• Pancreatitis
  
• Increased heart rate
  
• An increased risk of gallbladder disease
  
• Low blood sugar (hypoglycemia)
  
• Kidney problems
  
• Increased risk of thyroid cancer or tumors
  
• Allergic reactions like skin rash, swelling, breathing difficulties
  
  

Talk to your healthcare provider right away if you experience any side effects while taking oral semaglutide or semaglutide injections.

Who should take semaglutide for weight loss?

Semaglutide is FDA-approved as Wegovy for chronic weight management in patients without type 2 diabetes. When supplied as Ozempic or Rybelsus, its use as a weight loss aid is “off-label.”

Semaglutide is intended for adults with obesity (with a body mass index— BMI—of 30 kg/m2 or greater) or overweight adults (a BMI of 27 kg/m2 or greater) who also have weight-related health conditions such as hypertension (high blood pressure), high cholesterol, or obstructive sleep apnea.

Wegovy is approved for use in children over 12 with an initial BMI in the 95th percentile for their age.

Semaglutide is commonly prescribed as a subcutaneous injection, applied just under the skin. Those uncomfortable with needles should talk to the prescribing healthcare professional about alternatives to injectable weight loss medications.

Who should not take semaglutide for weight loss?

Semaglutide is an anti-obesity medication, meaning that it is specifically designed and prescribed to help people manage and reduce their body weight as a treatment for obesity. These medications are intended to assist individuals struggling to lose weight through diet and exercise alone. It is not prescribed to individuals who are of normal weight but want to lose a few pounds.

Before starting treatment with semaglutide, you should tell your provider about any medical conditions you have, any prescription drugs or supplements you are taking, and any allergies you may have. This information will help reduce the risk of any drug interactions or severe side effects.

• A history of pancreatitis
  
• Gallbladder problems
  
• Kidney disease
  
• Personal or family history of medullary thyroid carcinoma (MTC) (thyroid tumors)
  
• Multiple endocrine neoplasia syndrome type 2 (MEN2)
  
• Diabetic retinopathy
  
• High triglyceride levels
  
• Any digestive disorders
  
  

Additionally, pregnant women, women who are trying to conceive, or women who are breastfeeding may not be prescribed semaglutide.

What does “off-label” mean?

"Off-label" means a doctor uses a medication to treat a condition or symptom for which it was not explicitly designed or officially approved. This can happen for various reasons, such as when a doctor believes the medication may benefit a particular patient's condition, even though it hasn't been officially tested and approved for that specific use.

It's important to note that off-label use is legal and sometimes necessary in medical practice, allowing doctors to adapt treatments to individual patient needs. Patients should be informed when a medication is being used off-label and have the opportunity to discuss the decision with their healthcare provider.

What’s the difference between Ozempic, Wegovy, and Rybelsus?

Novo Nordisk produces three medications, Rybelsus, Ozempic, and Wegovy, all containing semaglutide. These three medications have different uses and methods of administration.

Rybelsus is designed to assist in regulating blood sugar levels for individuals with type 2 diabetes. It comes in a convenient pill form taken by mouth, enhancing sugar processing while supporting weight loss.

Ozempic is also used for managing blood sugar levels in type 2 diabetes but requires a weekly injection under the skin. It is beneficial for lowering blood sugar, aiding weight loss, and reducing the risk of cardiovascular issues in people with diabetes.

Wegovy, the third medication, is specifically intended for weight management in individuals who are either overweight or obese, regardless of whether they have diabetes. Administered via a weekly injection, Wegovy helps control weight by reducing hunger and increasing satisfaction from smaller meals.

In summary, Rybelsus and Ozempic primarily focus on blood sugar and weight control for individuals with type 2 diabetes. Wegovy is specifically designed for weight management in overweight or obese individuals with or without diabetes. Wegovy and Ozempic are injectable medications, while Rybelsus is supplied as an oral pill.

What are the alternatives to semaglutide?

There are a host of weight loss medications on the market. If you or your healthcare provider determine that semaglutide isn’t right for you, discuss these alternatives.

Tirzepatide, available as Mounjaro or Zepbound, is a medication used to manage both type 2 diabetes and obesity. It works by helping regulate blood sugar levels, curbing appetite, and slowing down stomach emptying. The brand name Zepbound, containing tirzepatide, is specifically approved for treating obesity in individuals without type 2 diabetes.

Liraglutide, marketed as Saxenda, is an FDA-approved treatment for obesity in adults and adolescents aged 12 and above. It belongs to a class of medications called GLP-1 receptor agonists. Liraglutide helps with weight loss by lowering blood sugar levels, suppressing appetite, and delaying stomach emptying.

Metformin, a prescription medication primarily used for diabetes management, can lead to weight loss in some individuals. It achieves this by regulating blood sugar levels and improving insulin sensitivity, which reduces the amount of sugar in the bloodstream.

Topiramate, available as Topamax, is an anticonvulsant drug that has weight loss effects in specific patients. Although its exact mechanism of action is not fully understood, it is believed to work by suppressing appetite, preventing excess fat storage, reducing particular fat and cholesterol levels, and potentially influencing the brain's reward system to reduce binge eating. It's important to note that while Topiramate is not FDA-approved as a weight loss medication, clinical trials have demonstrated significant weight loss in individuals taking it compared to those on a placebo.

Contrave is a combination drug composed of two active ingredients, bupropion, and naltrexone, each with distinct mechanisms contributing to its weight loss effects. Primarily, Contrave acts on the brain to control appetite and reduce cravings for high-calorie foods. It's essential to be aware that Contrave may have serious side effects, including the potential for suicidal thoughts.

How do I get a prescription for semaglutide?

Semaglutide is a prescription drug, meaning that you must have a written order from a licensed healthcare provider to get it. It cannot be purchased over the counter.

Semaglutide is available under its brand names Ozempic, Wegovy, and Rybelsus. These drugs come in various strengths and different forms (injectable vs. oral tablet). There are no generic versions of these drugs currently available.

Weight loss drugs are prescribed to individuals with obesity or individuals who are overweight and managing a weight-related health condition. If you are curious about semaglutide or any other weight loss drug, talk to your healthcare provider about whether or not these treatment options are right for you. You should also discuss the cost, potential side effects, and any concerns you may have.

How Sesame can help

Sesame offers a comprehensive online weight loss program to help you get started on your weight loss journey.

Sesame’s online weight loss program is a subscription which renews every 3 months and includes a video consultation with a weight loss doctor or specialist, a GLP-1 prescription (if appropriate), insurance coordination for medication coverage, and 90 days of unlimited messaging with your provider.

Note that all prescriptions are at the discretion of your healthcare provider.

Sources:

• Ghusn, W., De la Rosa, A., Sacoto, D., Cifuentes, L., Campos, A., Feris, F., Hurtado, M. D., & Acosta, A. (2022). Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity. JAMA.
• Lu, Y., Liu, Y., & Krumholz, H. M. (2022). Racial and Ethnic Disparities in Financial Barriers Among Overweight and Obese Adults Eligible for Semaglutide in the United States. Journal of the American Heart Association.
• Garvey, W.T., Batterham, R.L., Bhatta, M. et al. (2022). Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med.

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