Semaglutide for weight loss

If you’ve been trying to lose weight, you’ve probably heard of Ozempic and Wegovy. The two medications have surged in popularity over the last few years, thanks to their effectiveness in helping people shed excess weight — and keep it off.

But you may be less familiar with semaglutide, the active ingredient behind these two brand-name drugs (as well as another medication, called Rybelsus). So, how does semaglutide help with weight loss, and how effective is it, really? Read on as we explain. 

Semaglutide is the active ingredient in the brand name drugs Ozempic, Wegovy, and Rybelsus. Semaglutide is one of several glucagon-like peptide-1 (GLP-1) receptor agonists, along with liraglutide (brand names Saxenda, Victoza), dulaglutide (brand name Trulicity), and others. These medications mimic GLP-1, an incretin hormone produced naturally in your gut. 

GLP-1 plays a role in insulin and glucagon production and appetite regulation. Your gut produces the hormone after you eat to regulate your blood sugar levels. Essentially, GLP-1’s job is to tell your pancreas to release more insulin and hold off on glucagon, keeping blood sugar levels in check. These effects have led to the development of GLP-1 agonists as a treatment for type 2 diabetes. Semaglutide and other GLP-1 drugs effectively control blood sugar levels, a key component of managing type 2 diabetes.

Researchers soon discovered that as a GLP-1 receptor agonist, semaglutide has other effects on appetite that can be beneficial for people with type 2 diabetes, as well as those with obesity struggling to lose weight. 

For example, GLP-1 sends signals to your brain that impact both your appetite and your brain’s reward center regarding food. GLP-1 tells your brain when you’re full, reducing your appetite so you stop eating. And, semaglutide slows down how quickly food moves through your stomach (the longer it stays there, the sooner you feel full). These findings have led to the development of semaglutide as a standalone medication for weight management.

Semaglutide is currently available in two forms of administration. These include:

• Subcutaneous injections, like Wegovy and Ozempic

• Oral tablets, like Rybelsus

Subcutaneous semaglutide

Both Wegovy and Ozempic are injected subcutaneously on a weekly basis, under the skin of the thigh, abdomen, or upper arm. Each pen of Wegovy contains a single dose of the medication, while an Ozempic pen contains several doses of the medication, so you’ll need to replace the needle with each injection. You can inject Wegovy or Ozempic regardless of when you last ate. The important thing is to perform your injection on the same day each week, rotating through the injection sites each time. 

With either Wegovy or Ozempic, your health provider will likely have you start with a low dosage of 0.25 milligrams (mg) of semaglutide per week, before increasing your dosage every 4 weeks until the desired effect is achieved. This helps your body get used to the medication and reduces the intensity of side effects. Maintenance dosages of Ozempic include 0.5 mg, 1 mg, and 2 mg. The maintenance dosage of Wegovy is 1.7 mg or 2.4 mg. 

Oral semaglutide

Rybelsus tablets should be taken daily with water, at least 30 minutes before your first meal, beverage, or other medications. Rybelsus is available in 3 mg, 7 mg, and 14 mg dosage amounts.

Currently, semaglutide is FDA-approved for weight loss under the brand name Wegovy. Ozempic and Rybelsus, on the other hand, are FDA-approved for type 2 diabetes, although they may be prescribed off-label for weight management as well. Generic versions of semaglutide are not currently available, but compounded versions are available if you have difficulty filling a prescription of a brand name drug.

Semaglutide has shown to be very effective as a weight loss intervention, when paired with diet and exercise. In clinical trials, the average person taking semaglutide lost anywhere from 7% to over 17% of their body weight within a year and a half, depending on the dose of semaglutide. 

In one trial of nearly 2,000 adults with obesity, but not type 2 diabetes, those taking 2.4 mg of semaglutide (a typical maintenance dosage for Wegovy) lost nearly 15% of their body weight in about a year and a half. Those taking the placebo, on the other hand, lost less than 3%. Both groups also made lifestyle changes like reducing their diet by 500 calories and exercising for 150 minutes per week. In addition to losing more weight, the participants taking semaglutide shed almost 4 more inches off their waistlines, and improved their blood pressure and cholesterol to a larger extent. Individuals taking lower doses of semaglutide also experience significant weight loss. 

If you have type 2 diabetes, you may find that you lose less weight on semaglutide than people without diabetes. For example, in a trial of people with type 2 diabetes that observed the same time frame and the same dosage as the above trial above, those taking semaglutide lost a little less than 10% of their body weight. This is not unique to semaglutide, though. With most weight loss interventions, people with type 2 diabetes tend to lose less weight than those without diabetes. Still, the weight loss produced by semaglutide is more than enough to produce significant health benefits such as lower blood pressure, cholesterol, depression, and knee pain; as well as improved mobility, sexual function, fertility, and quality of life.

Researchers believe there are several reasons that make semaglutide so effective at weight loss. As a GLP-1 receptor agonist, semaglutide mimics GLP-1, the hormone that helps regulate your appetite. However, while natural GLP-1 only remains active in your body for about 2 minutes, semaglutide keeps working for about a week. 

GLP-1 drugs like semaglutide keep food in your stomach for longer, so you feel full sooner, and end up eating less. And, in addition to sending satiety signals to your brain telling you you’re full, semaglutide has been shown to reduce your appetite and even your desire for certain foods. In one study, after taking semaglutide for 12 weeks, people reported fewer cravings overall, and for fatty foods in particular.

The side effects of semaglutide include:

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

• Constipation

• Headache

• Fatigue

• Indigestion

• Dizziness

• Bloating

• Belching

• Flatulence

• Hypoglycemia (in people with type 2 diabetes)

• Stomach flu

• Gastroesophageal reflux disease (GERD)

• Cold-like symptoms

The above side effects were reported by at least 5% of people in clinical trials. Of these, the most common side effects are usually the gastrointestinal ones, such as nausea, diarrhea, vomiting, and constipation. 

The good news is that side effects are most common when you first begin taking semaglutide, and typically resolve and lessen with time as your body gets used to the medication. Semaglutide’s side effects also seem to be dose-dependent, meaning that they are more common with higher dosages of the medication, regardless of whether you take an injectable or oral form of semaglutide.

It’s impossible to predict which side effects you’ll experience if you take semaglutide, but some people may be more at risk than others. For example, people with type 2 diabetes may be more likely to experience low blood sugar on semaglutide, especially if they are also taking insulin, which also helps to lower blood sugar levels. To minimize this risk, your healthcare provider may adjust your insulin dosage.

People with certain health conditions, including a history of pancreatitis, diabetic retinopathy (vision loss or changes in people with type 2 diabetes), or kidney or gallbladder problems, may require extra monitoring while taking semaglutide to ensure the medication remains safe for them to use. People who are pregnant or breastfeeding (or plan to be in the near future), as well as those with a personal or family history of certain thyroid cancers, should not use semaglutide.

Serious side effects of semaglutide

In rare cases, semaglutide can cause serious side effects, including:

• Acute pancreatitis

• Acute gallbladder disease

• Acute kidney injury

• Allergic reaction

• Diabetic retinopathy

• Heart rate increase

• Severe hypoglycemia

• Suicidal behavior and ideation

Finally, animal studies have shown that semaglutide led to the development of thyroid tumors in rats. While it is not known if semaglutide has the same effect in humans, people with a personal or family history of medullary thyroid carcinoma, or those with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), should not use semaglutide.

Studies show that semaglutide can produce weight loss as high as 17.4% within about a year and a half, depending on the dosage you’re prescribed and whether or not you have type 2 diabetes. But, how soon can you expect to see results?

Semaglutide begins working as soon as you start taking it, and produces weight loss in a matter of weeks, according to studies of people with obesity. In one study, those taking 1 mg of semaglutide started eating about 24% less throughout the day, resulting in an average weight loss of 11 pounds, mostly from fat, within just 12 weeks. In another study, people taking 2.4 mg of semaglutide lost nearly 10% of their body weight within 20 weeks.

Research suggests that semaglutide keeps working as long as you keep taking it, helping you to not only lose weight, but to keep it off as well. In one study, individuals with overweight or obesity took 2.4 mg of semaglutide for 20 weeks, and lost 10.6% of their body weight, on average. When the researchers checked in 48 weeks later, they had lost even more weight — to the tune of an additional 7%–8%.

Because semaglutide is a prescription drug, you’ll need to meet with a licensed healthcare provider to get it. Semaglutide is prescribed to people with:

• Type 2 diabetes that isn’t adequately controlled with diet and exercise alone

• A body mass index (BMI) of 30 or higher (classified as obesity)

• A BMI of 27 or higher (classified as overweight) and a weight-related health condition such as diabetes, high blood pressure, or heart disease

If you fall into one or more of the above categories, your healthcare provider may recommend semaglutide as a treatment option. To get semaglutide, you’ll need to make an appointment with your primary care provider or a physician who specializes in obesity medicine. You can also get semaglutide online through the Ro Body program, a comprehensive, 12-month program that includes: 

• Metabolic testing (if needed)

• A personalized treatment plan

• 1:1 health coaching

• A step-by-step curriculum

• Ongoing support from your provider

• Insurance concierge services to help you get coverage

If you’re struggling to lose weight and keep it off, speak to your healthcare provider to see if semaglutide is right for you.

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Current version

November 15, 2023

Written by

Amelia Willson

Fact checked by

Felix Gussone, MD

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About the medical reviewer

Felix Gussone, MD, Ro

Felix Gussone is a physician, health journalist and a Manager, Medical Content & Education at Ro.