Healthcare provider talking to patient about Imcivree® vs. Wegovy® for weight loss

Imcivree® vs. Wegovy®

Written on September 27, 2023 by Lori Mulligan, MPH. To give you technically accurate, evidence-based information, content published on the Everlywell blog is reviewed by credentialed professionals with expertise in medical and bioscience fields.

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One of the main differences between Imcivree® (setmelanotide) vs. Wegovy® (semaglutide) is that Imcivree® is used solely in patients with certain genetic conditions. Let’s take a closer look at each of these drugs and compare Imcivree® vs. Wegovy®.


Setmelanotide (brand name Imcivree®) injection is used to help lose weight and keep the weight off in patients with obesity caused by proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), leptin receptor (LEPR) deficiency, or Bardet-Biedl syndrome (BBS). Your doctor will perform a test to check for POMC, PCSK1, or LEPR deficiency, or BBS before you use this medicine. This medicine is available only with your doctor's prescription.[1]

People with obesity due to POMC, PCSK1, or LEPR deficiency become severely obese at a young age. Patients are usually a normal weight at birth, but they gain excess weight because of a genetic defect (an imperfection or anomaly) that affects their level of hunger, ability to feel full or satiated, and energy output (metabolism). These conditions are very rare, with only around 150 reported in the medical literature for all three combined.

How Does Imcivree® Work?

Imcivree® works by activating areas in the brain that regulate appetite and fullness, causing patients with specific defects in these areas of the brain not to eat as much and to lose weight. The drug also increases resting metabolism (the number of calories the body burns at rest), which can contribute to weight loss. While Imcivree® leads to weight loss in patients with obesity associated with these conditions, it does not treat the genetic defects that cause the conditions or other symptoms or signs.

Imcivree® was evaluated in two 1-year studies. The first study enrolled patients with obesity and confirmed or suspected POMC or PCSK1 deficiency, while the second study enrolled patients with obesity and confirmed or suspected LEPR deficiency; all patients were six years or older. The effectiveness of Imcivree® was determined by the number of patients who lost more than 10 percent of their body weight after a year of treatment.

The effectiveness of Imcivree® was assessed in 21 patients, 10 in the first study and 11 in the second. In the first study, 80 percent of patients with POMC or PCSK1 deficiency lost 10 percent or more of their body weight. In the second study, 46 percent of patients with LEPR deficiency lost 10 percent or more of their body weight.

The study also assessed the greatest hunger in 16 patients over the previous 24 hours using an 11-point scale in patients 12 years and older. In both studies, some, but not all, of patients’ weekly average hunger scores decreased substantially from their scores at the beginning of the study. The degree of change was highly variable among patients.

What Are Common Side Effects Of Imcivree®?

The most common side effects of Imcivree® include injection site reactions, skin hyperpigmentation (skin patches that are darker than the surrounding skin), headache, and gastrointestinal side effects (such as nausea, diarrhea, and abdominal pain), among others. Spontaneous penile erections in males and adverse sexual reactions in females have occurred with treatment. Depression and suicidal ideation have also occurred with Imcivree®.[2]

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Wegovy® is the brand name for the high-dose injectable peptide hormone molecule known as semaglutide, a medication that was previously approved by the FDA under the brand names Rybelsus (oral) and Ozempic (lower-dose injection) for the treatment of type 2 diabetes. Injectable semaglutide eliminates the strict guidelines for ingesting on an empty stomach required by oral semaglutide, while the higher-dose Wegovy® allows for better crossing of the blood-brain barrier, which increases its weight-loss efficacy.

Semaglutide is in a class of medications known as glucagon-like peptide-1 receptor agonists, or GLP-1 RAs. GLP-1 is a hormone naturally released in the gastrointestinal tract in response to nutrient intake. It has multiple effects, including increasing insulin release from the pancreas, slowing down stomach emptying, and targeting receptors in the brain that cause appetite reduction. This results in a sensation of satiety, or fullness, lasting much longer than possible with natural GLP-1 hormone levels.

What Are The Risks And Benefits Of Wegovy®?

Phase 3 clinical trials of Wegovy®, dubbed the STEP (Semaglutide Treatment Effect in People with Obesity) trials, were conducted in a variety of clinical scenarios, each varying slightly in the study population and study design. The widely reported STEP 1 trial, the results of which were published in the New England Journal of Medicine, demonstrated an average of 14.9% body weight reduction after 68 weeks of therapy in those assigned to the medication group versus only 2.4% weight loss in those assigned to the placebo group. The average weight loss seen with existing anti-obesity medications is typically about 5% to 9%, while those engaged in lifestyle and behavioral therapy alone are expected to lose only 3% to 5% of their body weight.

The most common side effects of Wegovy® are nausea, diarrhea, vomiting, and constipation. The medication also comes with a warning for risk of a specific tumor of the thyroid, and thus, it is not recommended for those with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 (a genetic condition associated with endocrine tumors). It should be noted that tumors were only observed in animal studies and not seen in the human trials.[3]

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Our comprehensive Weight Care+ program pairs GLP-1 prescriptions with regular clinician care, lab testing, and support for related conditions. (Age 18+) Specifically, you get:

  • Access to GLP-1 prescriptions for qualified candidates
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  • Included quarterly at-home lab tests* or supplements
  • Lifestyle content and support for health conditions

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  1. Setmelanotide. Mayo Clinic. Last Updated on 2/1/23. Accessed on 9/12/23.
  2. FDA approves first treatment for weight management for people with certain rare genetic conditions. FDA. 11/27/2020. Accessed on 9/12/2023.
  3. Anekwe C. A new treatment for obesity. Harvard Health Publishing. 9/10/21. Accessed on 9/12/2023.
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