Clinical Overview: Semaglutide (Wegovy) for Weight Management

Semaglutide (Wegovy) is a glucagon-like peptide-1 (GLP-1) receptor agonist for chronic weight management in adult patients, when combined with a reduced calorie diet and exercise.¹

Patients with a body mass index (BMI) of or exceeding 30 kg/m² or with a BMI of or exceeding 27 kg/m² and have a least 1 weight-related comorbid condition, such as hypertension, diabetes, or dyslipidemia, can take semaglutide.

Semaglutide is also indicated with diet and exercise to improve blood sugar control in adults with type 2 diabetes mellitus. Semaglutide 1 mg injection (Ozempic) was initially approved as a treatment for type 2 diabetes in 2017.

Clinical trial²

Researchers conducted a double-blind trial with 1961 adult patients with a BMI of at least 30 or BMI at or exceeding 27 with comorbid conditions without diabetes. The 68-week trial randomized patients 2:1 to once weekly subcutaneous semaglutide 2.4 mg (n=1306) or placebo (n=655) and lifestyle interventions.

Primary endpoints were percentage change of weight at 68 weeks from baseline and percentage of patients achieving weight loss of at least 5% at week 68. Observed weight change at week 68 was 14.9% with semaglutide compared to placebo at 2.4%; 95% CI, −13.4 to −11.5; P<0.001.

A total of 86.4% of patients on semaglutide achieved a 5% weight loss at week 68 compared to 31.5% in the placebo group. Additionally, 69% of patients on semaglutide achieved a 10% weight loss compared to 12% in the placebo group. Gastrointestinal adverse events (AEs) were most common among patients receiving semaglutide than those receiving placebo; 74.2% versus 47.9%.

FDA approval

The FDA approved semaglutide (Wegovy) on June 4, 2021.³

Mechanism of action^1,4

Semaglutide increases insulin secretion and reduces glucagon secretion. As a GLP-1 receptor agonist, it acts in areas of the brain that regulate appetite and caloric intake.

Dosing¹

Semaglutide is a subcutaneous weekly injection with a dose escalation every 4 weeks until reaching the maintenance dose of 2.4 mg. Consider delaying the dose increase for an additional four weeks in patients who cannot tolerate the medication. Discontinue the medication if the patient cannot tolerate the maintenance dose of 2.4 mg. See Table 1 for dosing escalation schedule.

Missed dose⁴

If the patient misses a dose, administer as soon as possible within 5 days and then continue with the scheduled dose.If patients miss a dose and it is greater than 5 days, they should skip the missed dose and then continue with the next scheduled weekly dose. If the patient misses more than 2 consecutive doses, continue scheduled dosing.

Dosage form^1,4

Solution auto-injector, subcutaneous; Wegovy: 0.25 mg/0.5 mL (0.5 mL); 0.5 mg/0.5 mL (0.5 mL); 1 mg/0.5 mL (0.5 mL); 1.7 mg/0.75 mL (0.75 mL); 2.4 mg/0.75 mL (0.75 mL).

Renal and hepatic impairment¹

Semaglutide does not require dosing adjustments in patients with renal or hepatic impairment.

Administration⁴

Patients should administer the subcutaneous injection into the thigh, abdomen, or upper arm, weekly on the same day, rotating the sites. Health care providers should counsel patients to remove the pen cap and firmly press the device against the skin to release the medication when administering the dose. Patients must continue to press the device against the skin until the yellow bar stops moving before removing it. This may take 5 to 10 seconds.

AEs⁴

Semaglutide’s most common AEs are gastrointestinal in nature, resulting in nausea, diarrhea, vomiting, constipation, abdominal pain, dyspepsia, gastroenteritis, gastroesophageal reflux disease, and flatulence. Other AEs include dizziness, hypoglycemia in patients with type 2 diabetes, headache, and fatigue.

Warnings/Precautions^1,4

The following are disease-related AEs that may occur in patients taking semaglutide.

• Risk of thyroid c-cell tumors
• Acute pancreatitis
• Acute gallbladder disease
• Hypoglycemia
• Acute kidney injury
• Hypersensitivity reactions-anaphylaxis, angioedema
• Diabetic neuropathy in patients with type 2 diabetes
• Suicidal behavior and ideation

Drug Interactions¹

Semaglutide increases the risk of hypoglycemia when combined with other agents that cause hypoglycemia, such as sulfonylureas and insulin. A dose reduction of the concomitant agents may be necessary. Semaglutide can delay gastric emptying and can affect the absorption of oral medications. Avoid combining with other GLP-1 receptor agonists.

Contraindications1,4

Patients with a history or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 should not take semaglutide. Patients with a prior serious hypersensitivity reaction to semaglutide, such as anaphylaxis and angioedema, should also avoid semaglutide.

Pregnancy and Lactation^1,4

Semaglutide may cause fetal harm, therefore patients should discontinue use if they become pregnant. Females and males planning pregnancy should discontinue semaglutide 2 months before becoming pregnant because of semaglutide’s long half-life.

Pregnant women taking semaglutide and health care providers should contact Novo Nordisk at 800-727-6500 as part of the pregnancy exposure registry to monitor outcomes.

There are no data about semaglutide and risk in breastfeeding. Semaglutide was present in lactating rats. Consider semaglutide’s benefits and risks for the mother and the child.

Monitoring Parameters⁴

• HbA1c: Every 6 months if stable or quarterly if goals not met
• Heart rate
• Body weight
• Renal function
• Triglycerides
• Signs/symptoms of adverse reactions relevant to warnings/precautions
• Serum calcitonin or thyroid ultrasound

Storage^1,4

Store the Wegovy pen in the refrigerator, between 2°C to 8° (36°F to 46°F). Do not freeze and keep in the original packaging to avoid exposure to light.

About the Author

Helen Pervanas, PharmD, is a professor of Pharmacy Practice at MCPHS University.

References

1. Semaglutide (Wegovy™). Prescribing information. Novo Nordisk; 2021 Accessed March 3, 2022. https://www.novo-pi.com/wegovy.pdf
2. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021;384:989-1002. DOI: 10.1056/NEjMoa2032193.
3. FDA approval Wegovy™ Accessed March 3, 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014.
4. Semaglutide. Lexi-Drugs. Lexicomp Online. Wolters Kluwer Clinical Drug Information, Inc. Updated July 05, 2020. Accessed March 3, 2022. https://online-lexi-com.ezproxymcp.flo.org/