Semaglutide for Weight Loss

Wegovy, Rybelsus, or Ozempic? So many options to choose from! Scroll down and learn more about these semaglutide-using medications.

What is Semaglutide?

Semaglutide is an FDA-approved compound that is used in the management of type 2 diabetes and obesity. Semaglutide is available in different formulations, including subcutaneous injection (Ozempic and Wegovy) and oral tablet (Rybelsus). Ozempic and Rybelsus are FDA-approved for the management of type 2 diabetes and can be used off-label to treat obesity. Wegovy is the only form of semaglutide that is FDA-approved to manage obesity. The other difference between Wegovy and Ozempic is the dose; however, they are functionally the same medication.

How Does Semaglutide Work?

Semaglutide belongs to a class of drugs called GLP-1 receptor agonists, which mimic the effects of the naturally occurring hormone GLP-1. Semaglutide works by increasing insulin secretion, slowing digestion, and reducing appetite, which helps control blood sugar levels and promote weight loss.

Along with regulating insulin secretion and appetite, there are also anti-inflammatory effects. There are GLP-1 receptors in a multitude of organs. When activated, they lead to a decrease in the amount of pro-inflammatory receptors and an increase of anti-inflammatory cells in the body. This anti-inflammatory effect may provide benefits in reducing the risk of atherosclerosis (plaque formation in the arteries) and improving cardiovascular conditions (1).

This may also open avenues for using Semaglutide in other inflammatory conditions such as arthritis, polycystic ovarian syndrome, and psoriasis. However, more studies are needed to say for sure.

Who Qualifies for Semaglutide?

Currently, Rybelsus and Ozempic are FDA approved for managing type 2 diabetes. Therefore, if you are diagnosed with type 2 diabetes, you may be eligible to start either Rybelsus or Ozempic.

Wegovy has been FDA-approved in managing obesity; however, Rybelsus and Ozempic can also be used off-label. If you have a BMI greater than 30 or a BMI greater than 27 and have an obesity-related condition (diabetes, hypertension, dyslipidemia), you may be eligible to take either of these medications.

Due to the weight loss and anti-inflammatory effects, Semaglutide may also be used in patients with Polycystic Ovarian Syndrome (PCOS). A narrative review of evidence published in 2021 reviewed over 800 articles and found that there may exist a promising therapeutic role of GLP-1 agonist medications, like semaglutide, in managing PCOS (2). However, more extensive clinical trials are needed to establish a possible role.

Can Semaglutide Be Used for Weight Loss?

Multiple studies have been published looking at the weight loss benefits for diabetic and non-diabetic patients taking semaglutide. It should be noted that these medications should not substitute but be supplemented with a calorie restriction diet and regular exercise.

Ozempic has been shown to reduce body weight significantly for patients with diabetes. The SUSTAIN-6 trial published in 2016 showed that participants receiving weekly Ozempic (semaglutide) lost an average of 3-5 kg (8-11 lbs) after a two-year period (3). It is important to note that the participants were not enrolled in a diet and exercise program. Therefore, dieting and exercising regularly may lead to a more substantial weight loss effect when paired with Ozempic.

Rybelsus has also been shown to reduce body weight significantly. In the PIONEER-1 trial, the researchers examined how well Rybelsus managed diabetes in type 2 diabetics compared to a placebo (4). The researchers found a significant difference in body weight in the treatment group receiving a 14 mg dosage of Rybelsus. This group experienced a 2.6 kg (~5lb) difference after just 26 weeks. It should also be noted that the treatment group was not on a diet plan, exercising around 150 minutes per week, nor did a dietician follow them.

For Wegovy, the STEP 1 Trial was a large randomized control trial with around 1900 participants that examined how effective Wegovy (semaglutide) was at treating obesity in non-diabetic patients (5). Wegovy was given as a once-weekly pen injection starting at a low dose that was gradually increased to a maximum of 2.4mg over a period of 68 weeks. After 68 weeks, they found that participants taking Wegovy along with diet and exercise experienced a significant reduction in body weight (around 15%) compared to the placebo group.

Semaglutide vs Other GLP-1 Medications

Semaglutide vs Tirzepatide (Mounjaro)

Tirzepatide is a new dual-action GLP-1 and GIP agonist medication sold under the name Mounjaro. It is slightly different from semaglutide since it also works on the GIP (Gastric Inhibitory Peptide) receptors in the body, which increases the effectiveness of GLP-1. Tirzeptatide is also given as a once-weekly injection.

When tirzepatide was compared to semaglutide in the management of type 2 diabetes, researchers found that tirzepatide had a more significant effect on weight loss at all doses when compared to semaglutide (6). Higher doses of tirzepatide showed greater changes in body weight and BMI. It should be noted that these participants were not enrolled in a diet and exercise program. Therefore, an even greater weight loss effect may be seen with either of these medications if supplemented with a calorie-restricted diet and regular exercise (~150 minutes/week).

Semaglutide vs Liraglutide (Saxenda, Victoza)

Liraglutide is another type of GLP-1 agonist medication sold under Saxenda or Victoza. Liraglutide works very similarly to semaglutide and also has weight loss benefits. Saxenda is FDA-approved for the treatment of obesity, while Victoza is approved for the treatment of type 2 diabetes in patients ages ten and older. Both of these medications are once-daily injections.

When comparing semaglutide to liraglutide, semaglutide has been shown to have a more significant weight loss effect. In a study published in 2022 called the STEP-8 clinical trial, researchers compared the weight loss effect of semaglutide vs. liraglutide for non-diabetic patients struggling with obesity (7). Participants were given either semaglutide or liraglutide, were started on a calorie restriction diet and regular exercise, then were followed for a 68-week period. The researchers found that participants taking semaglutide noticed a 15.8% change in body weight, while participants taking liraglutide noticed a change of 6.4%.

Semaglutide vs Dulaglutide (Trulicity)

Dulaglutide is another type of GLP-1 agonist medication sold under the name Trulicity. It is currently FDA-approved for the treatment of type 2 diabetes and to prevent heart problems in people with type 2 diabetes. It can be used off-label in the treatment of obesity. It is also given as a once-weekly injection.

In a study published in 2018 called the SUSTAIN-7 trial, semaglutide was compared to dulaglutide in treating type 2 diabetes. This large clinical trial lasted around 40 weeks and involved over 100 hospitals worldwide. At the end of the study, participants taking semaglutide lost around 4.6 kg (~10 lbs), while participants taking dulaglutide lost 2.3 kg (~5 lbs)(7). Larger doses of either medication showed greater changes in body weight. The participants were not enrolled in a diet and exercise program, so there may be a more substantial change in body weight if this is supplemented as well.

Semaglutide Side Effects

The most common side effects when taking semaglutide are gastrointestinal side effects. This includes abdominal pain, nausea, vomiting, and diarrhea. The frequency of these symptoms varies between Ozempic, Wegovy, and Rybelsus, as well as with different dosages of these medications. When comparing the SUSTAIN-6 Trial to the PIONEER-1 trial, these gastrointestinal side effects were less common for people taking Rybelsus than those taking Ozempic (5-16% vs. 50-52%). People taking Wegovy compared to Ozempic (44% vs. 50-52%) had similar gastrointestinal side effects rates.

For all of these medications, the side effects were only mild to moderate in severity and went away over time. Animal studies examining the use of semaglutide in pregnant rats and rabbits have revealed a higher risk of fetal abnormalities and miscarriage. Though there are no human studies, these medications should be taken cautiously if you are pregnant or planning to become pregnant. Talk to your provider to determine if the benefits of taking semaglutide outweigh the risks to the fetus.

Semaglutide Dosage and Administration

As mentioned before, Ozempic, Rybelsus and Wegovy all use semaglutide as the active ingredient. The difference between these medications is that they are dosed and administered differently.

Wegovy is given as a once-weekly pen injection that is started at a dose of 0.25mg over four weeks. After four weeks, the dose will be increased to 0.5 mg. Each four-week treatment period, the dose can be increased to 1 mg, 1.7mg to a maximum of 2.4mg. A dose of 2.4 mg is considered the “maintenance dose” that you would continue with.

Similarly, Ozempic is a once-weekly pen injection starting at 0.25 mg. After 4 weeks, the dose will be increased to 0.5mg. The dose can be increased to 1mg or to a maximum of 2 mg after every four weeks. This makes it different from Wegovy since the dosing is different.

Wegovy and Ozempic are injected into the abdomen, thigh, or upper arm. Make sure to rotate the injection locations with each dose. It can be taken with or without a meal. If you miss a dose, take it at least 2-5 days after the day you were supposed to take it.

Rybelsus is a once-daily tablet that is started at a dose of 3 mg for 30 days. After 30 days, the dose can be increased to 7 mg or to a max of 14 mg. Rybelsus should be taken 30 minutes before your first meal, beverage, or oral medication. You should take Rybelsus with water. You should not split, crush or chew the tablet.

Semaglutide Contraindications and Warnings

Pancreatitis

Pancreatitis occurs when the pancreas becomes inflamed. This is an infrequent but potential side effect of semaglutide. If you have a history of pancreatitis, please inform your provider before starting semaglutide.

Hypoglycemia (Low Blood Sugar)

Since semaglutide increases insulin secretion, there is a risk that your blood sugar can be lowered to dangerous levels. This is known as hypoglycemia. If you have a history of hypoglycemia or are currently using insulin, you must inform your provider before starting semaglutide.

Serious Allergic Reaction

You may experience a severe allergic reaction to semaglutide when first taking it. Signs of a severe allergic reaction include swelling of your face, lips, tongue, or throat, problems breathing or swallowing, severe rash or itching, fainting or feeling dizzy, and very rapid heartbeat. Let your provider know immediately if you have experienced this with other GLP-1 medications or are currently experiencing this when taking semaglutide.

Kidney Disease

Though semaglutide is safe for people with kidney disease, the stomach problems associated with semaglutide may lead to fluid loss by vomiting, nausea, or vomiting. If you do have kidney problems, it is essential to stay hydrated while on semaglutide. If the gastrointestinal side effects of semaglutide are preventing you from adequately staying hydrated, then let your provider know immediately.

Severe Stomach Problems

The most common side effect of Semaglutide is gastrointestinal upset, which includes stomach ache, nausea, diarrhea, vomiting, and loss of appetite. If these symptoms become so severe that they significantly affect your daily life or ability to eat regularly, then let your provider know.

Changes in Vision

For patients with a history of diabetic retinopathy, there is a chance that your vision can worsen when taking semaglutide. If you do have a history of diabetic retinopathy, then let your provider know before starting semaglutide.

Gallbladder Disease

Semaglutide can also cause some gallbladder issues along with other gastrointestinal side effects. Since semaglutide can decrease food movement through the gastrointestinal system, it can also reduce the gallbladder's function. This can lead to gallstone formation, which can block the release of bile, leading to the inflammation of the gallbladder.

If you have a history of gallstones or cholecystitis (inflammation of the gallbladder), then let your provider know before starting semaglutide. If you have had your gallbladder removed in the past, then you can still take semaglutide.

Thyroid Cancer or Family History of MEN-2

Though very rare, there is a risk of the development of a specific type of thyroid cancer when taking Semaglutide, called Medullary Thyroid Cancer. If you have a history of medullary thyroid cancer or a family history of Multiple Endocrine Neoplasia Cancer Syndrome Type 2 (MEN-2), let your provider know before starting semaglutide. MEN-2 is a genetic cancer syndrome that puts a patient at risk for the development of Medullary Thyroid Cancer, which is why patients with this syndrome should avoid taking semaglutide.

Pregnancy

The use of Semaglutide is not well studied. The current guidelines suggest that the weight loss effects of Wegovy may not benefit you during pregnancy and can potentially cause harm to the fetus. Therefore you should avoid taking Semaglutide for weight loss alone if you are pregnant or are planning on becoming pregnant. For Ozempic and Rybelsus, you should discuss with your provider if the benefits of treatment for Type 2 diabetes out weight the risks for the fetus.

Semaglutide Coverage and Cost

The cost of semaglutide can be very expensive. The average cost for Rybelsus and Ozempic can range from $900-950 for a month’s supply. For Wegovy, it can cost upwards of $1400. Therefore, you should discuss which medication your plan covers with your insurance provider or if you qualify for any benefit plans.

You may be eligible for a Wegovy Savings Coupon to help lower the price of a 28-day supply to $0 for up to 12 refills depending on your insurance plan. You can use the following link to check if your insurance plan covers Wegovy.

Depending on your insurance plan, you may be eligible for an Ozempic Savings Card, where you can pay as little as $25 for a 1,2, or 3-month prescription. Around 92% of commercial insurance plans cover Ozempic, so your plan can help with the costs. You may also be eligible for the Patient Assistance Program offered by NovoCare, where you may receive Ozempic for free!

If you are interested in Rybelsus, there is a Rybelsus savings Card that you can apply for, where you can pay as low as $10 for a 30 - 90 day supply of medication. For Rybelsus, around 99% of commercial insurance plans can help cover the costs. There is also the option to apply for the Patient Assistance Program through NovoCare.

Where Can I Get Semaglutide?

If you would like to learn more about GLP-1 medications or want to see if you might be eligible for medication-assisted weight loss, check out Mochi Health, where board-certified obesity medicine physicians can offer expertise in this realm!

Mochi Health is a virtual obesity medicine practice that connects you with medical providers, like licensed physicians and nurse practitioners, to help you optimize your weight loss journey. We provide monthly video chats with actual medical providers to provide guidance about weight management and to get you started on prescription weight loss medications to supplement your weight loss plan.

Frequently Asked Questions

Check out our Mochi Health Blogs to learn about different topics on weight loss medications.

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References

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8. Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, Viljoen A; SUSTAIN 7 investigators. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomized, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018 Apr;6(4):275-286. doi: 10.1016/S2213-8587(18)30024-X. Epub 2018 Feb 1. PMID: 29397376.