Wegovy (semaglutide) - 2 indications

Scroll down for more information on each indication:

• to reduce excess body weight and maintain long-term weight reduction in patients aged 12 years and older with obesity and adults with overweight in the presence of at least one weight-related comorbid condition; approved June of 2021
• to reduce the risk of major adverse cardiovascular events in adults with established cardiovascular disease and either obesity or overweight; approved March of 2024

General Information

Wegovy (semaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist. Wegovy works by mimicking the GLP-1 hormone that targets areas of the brain that regulate appetite and food intake.

Wegovy is specifically indicated:

• to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 12 years and older with obesity and adults with overweight in the presence of at least one weight-related comorbid condition
• to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight

Dosing/Administration

Wegovy is supplied as an injection for subcutaneous administration. Administer Wegovy in combination with a reduced-calorie diet and increased physical activity. Administer Wegovy once weekly, on the same day each week, at any time of day, with or without meals. Inject Wegovy subcutaneously in the abdomen, thigh, or upper arm. The time of day and the injection site can be changed without dose adjustment.

Adults:

Initiate Wegovy with a dose of 0.25 mg injected subcutaneously once-weekly and follow the dose escalation schedule below to minimize gastrointestinal adverse reactions:

• Weeks 1 through 4: Weekly dose: 0.25 mg
• Weeks 5 through 8: Weekly dose: 0.5 mg
• Weeks 9 through 12: Weekly dose: 1 mg
• Weeks 13 through 16: Weekly dose: 1.7 mg
• Week 17 and onward: 1.7 or 2.4 mg Maintenance dose

If patients do not tolerate a dose during dose escalation, consider delaying dose escalation for 4 weeks.

The maintenance dose of Wegovy is 2.4 mg injected subcutaneously once-weekly. If patients do not tolerate the maintenance 2.4 mg once-weekly dose, the dose can be temporarily decreased to 1.7 mg once-weekly, for a maximum of 4 weeks. After 4 weeks, increase Wegovy to the maintenance 2.4 mg once-weekly.

Discontinue Wegovy if the patient cannot tolerate the 2.4 mg dose.

In patients with type 2 diabetes, monitor blood glucose prior to starting Wegovy and during Wegovy treatment.

Pediatrics:

Administer Wegovy according to the schedule below. If patients do not tolerate a dose during dosage escalation, consider delaying dosage escalation for 4 weeks. The 0.25 mg, 0.5 mg, and 1 mg once-weekly dosages are initiation and escalation dosages and are not approved as maintenance dosages.

Initiation (Weeks 1-4): 0.25 mg

Escalation:

• Weeks 5-8: 0.5 mg
• Weeks 9-12: 1 mg
• Weeks 13-16: 1.7 mg

Maintenance (Weeks 17 and onward): 2.4mg 

If patients do not tolerate the 2.4 mg once-weekly maintenance dosage, the maintenance dosage may be reduced to 1.7 mg once weekly. Discontinue if the patient cannot tolerate the 1.7 mg once-weekly dosage.

Mechanism of Action

Wegovy (semaglutide) is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1. GLP-1 is a physiological regulator of appetite and caloric intake, and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation. Animal studies show that semaglutide distributed to and activated neurons in brain regions involved in regulation of food intake.

The exact mechanism of cardiovascular risk reduction has not been established.

Side Effects

Adverse effects associated with the use of Wegovy may include, but are not limited to, the following:

• nausea
• diarrhea
• vomiting
• constipation
• abdominal pain
• headache
• fatigue
• dyspepsia
• dizziness
• abdominal distension
• eructation
• hypoglycemia in patients with type 2 diabetes
• flatulence
• gastroenteritis
• gastroesophageal reflux disease

Indication 1 - to reduce excess body weight and maintain long-term weight reduction in obese patients >12 years of age and overweight adults with at least one weight-related comorbid condition

The FDA approval was based on four 68-week trials. Three were randomized, double-blind, placebo-controlled trials (including 16 weeks of dose increases) and one was a double-blind, placebo-controlled, randomized withdrawal trial in which patients receiving Wegovy either continued with the treatment or switched to a placebo. More than 2,600 patients received Wegovy for up to 68 weeks in these four studies and more than 1,500 patients received placebo.

The largest placebo-controlled trial enrolled adults without diabetes. The average age at the start of the trial was 46 years and 74% of patients were female. The average body weight was 231 pounds (105 kg) and average BMI was 38 kg/m2. Individuals who received Wegovy lost an average of 12.4% of their initial body weight compared to individuals who received placebo. Another trial enrolled adults with type 2 diabetes. The average age was 55 years and 51% were female. The average body weight was 220 pounds (100 kg) and average BMI was 36 kg/m2. In this trial, individuals who received Wegovy lost 6.2% of their initial body weight compared to those who received placebo. In the STEP 1 trial, results also showed that patients taking Wegovy achieved an average weight loss of 14.9% of body weight at 68-weeks vs. 2.4% for placebo. In addition, 83.5% of patients achieved 5% or more body weight reduction in the Wegovy arm vs. 31.1% for placebo.

Indication 2 -  to reduce the risk of major adverse cardiovascular events in adults with established cardiovascular disease and either obesity or overweight

approved March of 2024