Imcivree Vs. Wegovy^®: Drug Comparison

Imcivree^® (setmelanotide) is a medication used to treat rare genetic conditions that cause severe obesity by activating the melanocortin-4 receptor (MC4R), which helps regulate hunger and energy expenditure. Its FDA-approved indications include the treatment of obesity due to certain genetic conditions, including POMC (pro-opiomelanocortin gene) deficiency, LEPR (leptin receptor gene) deficiency, and Bardet-Biedl syndrome. Imcivree is available as a subcutaneous injection, typically administered daily. Common side effects include injection site reactions, darkening of the skin, and nausea, with more serious risks including depression and suicidal thoughts.

Wegovy^® (semaglutide) is an injectable medication approved for chronic weight management in adults with obesity or overweight with at least one weight-related condition, such as hypertension, type 2 diabetes, or high cholesterol. It works by mimicking the hormone glucagon-like peptide-1 (GLP-1), which regulates appetite and food intake, leading to reduced calorie consumption and significant weight loss. Wegovy^® is administered once weekly and is intended to be used in conjunction with a reduced-calorie diet and increased physical activity. Common side effects include nausea, diarrhea, vomiting, and constipation. It should be used with caution in patients with a history of pancreatitis and is not recommended for use in pregnant or breastfeeding individuals​.

Melanocortin 4 (MC4) receptor agonist

Glucagon-like peptide-1 (GLP-1) receptor agonist

Imcivree (setmelanotide) is indicated for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to:

• Pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1, or LEPRgenes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS)

• Bardet-Biedl syndrome (BBS)

Wegovy^® (semaglutide) is indicated in combination with a reduced calorie diet and increased physical activity:

• 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

• To reduce excess body weight and maintain weight reduction long term in:

  • Adults and pediatric patients aged 12 years and older with obesity

  • Adults with overweight in the presence of at least one weight-related comorbid condition

• Typically taken as an injection once daily

• Comes in a 10 mg/mL solution in a 1 mL multiple-dose vial

• Typically taken as an injection once weekly

• Comes in single-dose pens that deliver 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, or 2.4 mg per injection

The most common adverse reactions (incidence ≥20%) included:

• Skin hyperpigmentation

• Injection site reactions

• Nausea

• Headache

• Diarrhea

• Abdominal pain

• Vomiting

• Depression

• Spontaneous penile erection

Most common adverse reactions (incidence ≥5%) in adults or pediatric patients aged 12 years and older are:

• Nausea

• Diarrhea

• Vomiting

• Constipation

• Abdominal pain

• Headache

• Fatigue

• Indigestion

• Dizziness

• Abdominal distension

• Belching

• Low blood sugar in patients with type 2 diabetes

• Flatulence

• Inflammation of the digestive system

• Gastroesophageal reflux disease (heartburn)

• Inflammation of the nasal cavities and back of the throat

• Prior serious hypersensitivity to setmelanotide or any of the excipients in Imcivree

• Personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2

• Known hypersensitivity to semaglutide or any of the excipients in Wegovy^®

• Drug interactions: Wegovy^® delays gastric emptying. May impact absorption of concomitantly administered oral medications

• Disturbance in sexual arousal

• Depression and suicidal ideation

• Hypersensitivity reactions

• Skin pigmentation and darkening of pre-existing nevi

• Pregnancy: Risk of serious adverse reactions due to benzyl alcohol preservative in neonates and low birth weight infants

• Breastfeeding: Not recommended when breastfeeding

• Acute pancreatitis

• Acute gallbladder disease

• Low blood sugar: Concomitant use with insulin or an insulin secretagogue may increase the risk of low blood sugar, including severe low blood sugar

• Acute kidney injury

• Hypersensitivity reactions

• Diabetic retinopathy complications in patients with type 2 diabetes

• Heart rate increase

• Suicidal behavior and ideation

• Pregnancy: May cause fetal harm. When pregnancy is recognized, discontinue Wegovy^®

• Females and males of reproductive potential: Discontinue Wegovy^® at least 2 months before a planned pregnancy because of the long half-life of semaglutide

WARNING: RISK OF THYROID C-CELL TUMORS

In rodents, semaglutide causes thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Wegovy^® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined.

Wegovy^® is contraindicated in patients with a personal or family history of MTC or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and symptoms of thyroid tumors.

*This information is from the label for brand name Imcivree^®. See the Full Prescribing Information for more complete information.

*This information is from the label for brand name Wegovy^®. See the Full Prescribing Information for more complete information. Semaglutide, the active ingredient in Wegovy^®, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient semaglutide.