Focus on Pharmacology: Semaglutide

Semaglutide, which is sold under the brand names Ozempic, Wegovy and Rybelsus, has become increasingly popular and is a medication you are likely to encounter in the clinical setting and when reviewing your patient’s medical histories. In this article, you’ll learn the key things to know about semaglutide using the Straight A Nursing DRRUGS framework.

D: Drug Class

Semaglutide is in a pharmacologic class called glucagon-like peptide-1 receptor agonists, more commonly known as GLP-1 agonists. These medications work by increasing intracellular cyclic AMP, which causes insulin to be released when blood glucose levels are elevated. The insulin release ceases as the blood glucose level approaches a normal range, which reduces or alleviates the risk of hypoglycemia. Semaglutide also decreases the secretion of glucagon and delays gastric emptying which helps suppress appetite.

R: Routes of Administration

Semaglutide can be taken as a subcutaneous injection or by mouth. Note that injected semaglutide has 89% absorption, compared to only 0.4 to 1% absorption when taken orally. What this means is that oral doses will be significantly higher than injectable doses. A key advantage of the oral formulation is that it makes this medication available to individuals who are unwilling or unable to self inject. For example, an individual with severe rheumatoid arthritis, low visual acuity, cognitive impairment, peripheral neuropathy, or hemiparesis may find injecting a medication challenging. 

It is also important to note that despite its lower absorption, the oral preparation is no less effective in lowering blood glucose levels or reducing the patient’s weight. 

R: Regular dose range

When taken PO, the dose for an adult is 3 to 14 mg, with the dose starting out low and increasing slowly as needed to achieve glycemic control. The PO formulation of semaglutide (Rybelsus) is taken daily.

Subcutaneous doses are smaller, ranging from 0.25 mg to 2.4 mg and are injected weekly (Ozempic and Wegovy).

U: Uses

Semaglutide has two main uses – as a treatment for type 2 diabetes and as a weight loss medication. Initially it was approved to treat type 2 diabetes in December 2017. However, during the drug’s clinical trials, it was noted that, in addition to reducing blood glucose levels, it also caused weight loss. The medication was then approved by the FDA as a treatment for obesity in adults in June 2021. Subsequently, it was approved for use in children aged 12 years and older in December 2022.

Another benefit is that semaglutide has been shown to reduce inflammation and c-reactive protein in parallel with weight loss. This is significant mainly because inflammation is associated with many pathological processes, and CRP levels are specifically correlated with cardiovascular risk. For this reason, it is used in patients with type 2 diabetes and cardiovascular disease to decrease their risk for cardiovascular complications.

The three formulations of semaglutide are:

• Ozempic – Available as subcutaneous injection, Ozempic is approved for the treatment of type 2 diabetes in coordination with diet and exercise and also to lower cardiovascular risk in patients with type 2 diabetes and cardiovascular disease. However, you will see it used off-label for weight loss. This has led to shortages of Ozempic, meaning those who rely on it to treat diabetes have difficulty filling their prescriptions.
• Rybelsus – Rybelsus is the PO formulation of semaglutide. It is approved for the treatment of type 2 diabetes in coordination with diet and exercise.
• Wegovy – Available as a subcutaneous injection, Wegovy is approved for use in weight loss in individuals with a BMI of 27 or greater and at least one weight-related condition such as hyperlipidemia, hypertension, or type 2 diabetes.

G: Guidelines

Administration – PO semaglutide is administered at least 30 minutes prior to taking any medications or eating the first meal of the day, and should be taken with water only. Subcutaneous formulations are stored in the refrigerator and administered once a week without regard to meals. Patients are instructed to inject in the upper arm, abdomen or thigh and they should rotate sites each week. 

If your patient is taking both semaglutide and insulin, be sure they understand not to mix these two medications together and to avoid using injecting sites near one another.

Safety considerations – Unlike insulin and other medications used to treat hyperglycemia, semaglutide does not put the patient at risk for hypoglycemia on its own. However, hypoglycemia can occur when it is used in coordination with other antidiabetic medications such as sulfonyureas (ex: Glipizide) or insulin.

Semaglutide is contraindicated in type 1 diabetes, DKA and in those with a history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN2). It is used with extreme caution or not at all in individuals with a history of diabetic retinopathy, pancreatitis, or suicidal attempt/ideation. It is also used cautiously in patients who have had a hypersensitivity reaction to other GLP-1 receptor agonists such as dulaglutide (Trulicity) or exenatide (Byetta).

Semaglutide is generally avoided during pregnancy and lactation, with insulin being the preferred method of blood glucose control in these situations.

Another key safety factor comes into play with anesthesia. Because semaglutide causes delayed gastric emptying, studies show that food remains in the stomach longer than standard fasting guidelines allow for. Patients should be advised to inform all health care providers, including surgeons and anesthesiologists, that they are taking semaglutide. A longer fasting period may be advised and the patient will likely be instructed to stop taking their medication prior to the procedure in order to prevent aspiration.

Assessment – Key assessments for a patient taking semaglutide are blood glucose levels and weight. It’s also important to monitor for signs of hypoglycemia when other antidiabetic medications are being utilized. 

Drug-to-drug interactions – The main drug-to-drug interactions involve concurrent use with insulin and/or medications that increase insulin secretion such as sulfonylureas. When used together, the risk for hypoglycemia is pronounced. It’s also important to note that the delayed gastric emptying that occurs with semaglutide can lead to altered absorption of other medications taken by mouth. 

S: Side Effects

Serious side effects, though rare, can occur with semaglutide. These include pancreatitis, gastric paralysis, bowel obstruction, gallbladder complications, hypersensitivity reactions, thyroid cancer, and suicidal ideation/attempt. More common adverse effects include abdominal pain, nausea/vomiting, diarrhea, constipation, headache and fatigue. The medication can also cause tachycardia, so be sure to monitor the patient’s heart rate when taking semaglutide. In addition, acute kidney injury can occur so the patient should report any concerning signs and symptoms such as flank pain, decreased urine output or hematuria.

In addition, patients taking these medications may be at higher risk for aspiration while under anesthesia due to delayed gastric emptying. The American Society of Anesthesiologists advises patients to stop the injected medication for at least a week prior to any sedating procedures. Ongoing research in this area may provide standardized guidelines in the future.

Another effect of using semaglutide you may have seen in the news and on social media is “Ozempic face” which was first described by dermatologist Dr. Frank after treating many patients with this symptom. It is thought to be due to the rapid weight loss that occurs with the medication which leads to a swift reduction in facial fat. With this loss of fat, the individual’s skin loses elasticity and the appearance changes. Common signs of semaglutide’s effect on the face include more lines and wrinkles, saggy or loose skin, and a hollowed-out appearance. Individuals concerned about these effects may choose to lower their dose in efforts to lose weight more slowly, increase fluid and protein intake, or switch to another method for weight loss altogether.

I hope this brief overview of semaglutide has increased your understanding of this popular medication. For more pharmacology lessons, click here.

I also want to let you know about an easy way to review pharmacology concepts on-the-go, and that’s with my audio based program, Fast Pharmacology. In this program, I review key pharmacology concepts and over 80 drug classes in 5 minutes or less. This program is perfect for use while you’re in nursing school, studying for NCLEX, or wanting to gain confidence administering medications as a working nurse. Learn more here!

Take this topic on the go by tuning in to episode 325 of the Straight A Nursing podcast. Listen from any podcast platform, or straight from the website here.

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Last Updated on January 11, 2024 by Maureen Osuna, MSN, RN