Wegovy From Novo Nordisk

The FDA recently approved an additional indication for semaglutide (Wegovy) from Novo Nordisk to reduce the risk of major cardiovascular events such as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in adults with established cardiovascular disease and with either obesity or overweight. The approval states that semaglutide should be used with increased physical activity and a reduced-calorie diet, and it carries the limitation that the medication should not be coadministered with other semaglutide-containing products or glucagon-like peptide-1 receptor (GLP-1) agonists. Semaglutide was previously approved to reduce excess body weight and maintain longterm weight reduction in adults and children 12 years and older with obesity and in adults with overweight and at least 1 weight-related comorbidity.^1,2

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PHARMACOLOGY AND PHARMACOKINETICS

Semaglutide is a GLP-1 receptor agonist, and its exact mechanism in the role of cardiovascular risk reduction has not been established. Semaglutide reaches maximum plasma concentrations 1 to 3 days after administration and displays an elimination half-life of approximately 1 week.¹

DOSAGE AND ADMINISTRATION

Semaglutide should be injected subcutaneously once weekly in the abdomen, thigh, or upper arm on the same day each week, at any time, without regard to meals. The recommended titration schedule is 0.25 mg weeks 1 through 4, 0.5 mg weeks 5 through 8, 1 mg weeks 9 through 12, and 1.7 mg weeks 13 through 16. The target maintenance dose from week 17 and on is 2.4 mg, which may be reduced to 1.7 mg for adults who cannot tolerate the 2.4-mg dose. Patients with type 2 diabetes should monitor blood glucose before and during treatment with semaglutide.¹

CLINICAL TRIALS

Semaglutide was evaluated in the double-blind, multicenter, multinational, placebo-controlled phase 3 SELECT trial (NCT03574597) in adults with established cardiovascular disease, an initial body mass index of greater than or equal to 27 kg/m2, and without diabetes. Participants were randomly assigned to receive either semaglutide 2.4 mg or placebo. The primary end point was major adverse cardiovascular events (MACE), which was the time to first occurrence of a 3-part composite outcome of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The trial found that treatment with semaglutide significantly reduced the risk for first occurrence of MACE, with the primary composite outcome occurring in 6.5% of patients using semaglutide and 8.0% of those using placebo. The estimated relative risk reduction was 20%.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Semaglutide carries a boxed warning stating that it causes thyroid C-cell tumors in rodents. It is not known whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans. Patients should be counseled regarding the potential risk of MTC and symptoms of thyroid tumors.

Semaglutide is contraindicated in patients with a family or personal history of MTC, multiple endocrine neoplasia syndrome type 2, and a known hypersensitivity to the medication or any of its components.

Semaglutide should be discontinued immediately if acute pancreatitis is suspected. Acute gallbladder disease has occurred in clinical trials. Concomitant use with insulin or an insulin secretagogue may increase the risk of hypoglycemia. Because acute kidney injury has occurred, renal function should be monitored when initiating or escalating doses of semaglutide in patients with severe adverse gastrointestinal reactions. Anaphylactic reactions and angioedema have been reported. Diabetic retinopathy complications have been reported in patients with type 2 diabetes. Treatment with semaglutide was associated with an increased resting heart rate. Patients should be monitored for depression or suicidal thoughts, and semaglutide should be discontinued if symptoms develop.

Semaglutide should not be used during pregnancy or within 2 months before planned pregnancy. Because it delays gastric emptying, semaglutide may affect the absorption of concomitantly administered oral medications.

The most common adverse reactions are abdominal distension, abdominal pain, constipation, diarrhea, dizziness, dyspepsia, eructation, fatigue, flatulence, gastroenteritis, gastroesophageal reflux disease, headache, hypoglycemia in patients with type 2 diabetes, nasopharyngitis, nausea, and vomiting.¹

REFERENCES

1. Wegovy. Prescribing information. Novo Nordisk Inc; 2024. Accessed May 30, 2024. https://www.novo-pi.com/wegovy.pdf

2. Wegovy receives FDA approval for cardiovascular risk reduction in adults with known heart disease and overweight or obesity. News release. Novo Nordisk. March 8, 2024. Accessed May 30, 2024. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=167031