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Imcivree (Setmelanotide) for Weight Loss: Does It Work?

<p>Imcivree (Setmelanotide) for Weight Loss: Does It Work?</p>
Dr. Constance Odom, MD Picture of Dr. Constance Odom, MD

Medically reviewed by

Written by our editorial team.

Last Edited 8 min read

Obesity is fast becoming one of the world's most discussed public health problems, with prevalence numbers reaching an all-time high in most countries. The issue has far-reaching effects on both the body and mind and can often lead to the development of several other conditions that can cause the body to become a ghost of its former self. Luckily, obesity can be combated using drugs such as Imcivree. This drug is a newer addition to the obesity treatment list, only recently gaining FDA approval for use in patients with obesity due to genetic conditions. Since the drug is essentially new to the market, it's only natural to wonder if it works.

Below we aim to expand on just that by sifting through evidence from real-life clinical trials and studies.

A Basic Overview of Imcivree

Imcivree is an injectable prescription weight management drug designed by Rhythm Pharmaceuticals. The drug is the first and only FDA-approved treatment created to target a flawed MC4R pathway, which is the root cause of specific obesity and unexplainable hunger.

The drug is synthetically based, meaning it's 100% man-made and falls under the melanocortin-4 (MC4) receptor agonist medication class. It uses the active ingredient setmelanotide to induce weight loss in individuals who have obesity caused by genetic conditions and cannot be used by those who do not meet this criterion. 

It comes in a liquid form and is prefilled into injectable pens, which need to be administered subcutaneously (under the skin) in the abdomen, thigh, or arm. The administration site should be rotated each day to prevent skin irritation. The formula is short-acting, meaning its effects last for a short period, so daily administration is needed. 

The drug can be safely used in short-term or chronic weight loss plans, and users will see a noticeable difference in their weight in 12-16 weeks. Users should ideally lose 5% of their body weight or body mass index (BMI) during this time. This weight loss result can vary slightly from patient to patient. 

Who Can Use Imcivree (setmelanotide)?

Imcivree is an effective weight loss medication that can be used by individuals 6 years and older diagnosed with genetic conditions that cause excessive or uncontrollable weight gain. These conditions do not respond to traditional weight loss initiatives such as a controlled diet and increased exercise alone. The active ingredient, setmelanotide, works against the primary factors that fuel weight gain, such as issues with the following:

  • Metabolisms

  • Food cravings

  • Appetite control

  • Feelings of fullness

  • Body-fat distribution

  • Fat-to-energy conversion

The issues above are present in obesity caused by genetic conditions such as:

  • POMC (Proopiomelanocortin) deficiency

Genetic changes in the POMC gene cause POMC deficiency. The deficiency is characterized by severe obesity that begins as early as infancy. Affected individuals are typically of normal weight at birth but constantly experience feelings of hunger, leading to excessive feeding and weight gain during the first year of life, continuing throughout childhood and adulthood. 

  • PCSK1 (Proprotein convertase subtilisin/kexin type 1) deficiency 

A variant in the PCSK1 gene causes PCSK1 deficiency. The deficiency is noticed during infancy and causes severe intestinal malabsorption. This leads to GI distress as food runs through the bowels too fast, and nutrients are not absorbed. Children with this deficiency require controlled nutrition, causing hyperphagia, which causes intense hunger and excessive eating—obesity. 

  • LEPR (Leptin receptor) deficiency

LEPR deficiency affects the function of leptin which causes constant hunger, leading to high food consumption and weight gain. It causes severe obesity that can be noticed in the first few months of life.

  • BBS (Bardet-Biedl) syndrome 

This condition affects multiple systems in the body, one of them being disturbances in appetite-regulating hormones. This causes excessive eating, weight gain, and obesity.

How Does Imcivree Work?

The efficacy or proof behind whether a product works can typically be deduced from its mechanism of action. The mechanism of action refers to how a pharmaceutical product works to carry out its function. While the terminology may sound a bit confusing, it's actually quite simple to grasp once the basics are understood. 

Traditional weight loss aids eliminate fat stores and manage weight using simple methods that don't delve into correcting issues that fuel weight gain. Imcivree, on the other hand, takes an in-depth approach that involves manipulating the brain and body into eliminating fat in a natural yet effective way that does not worsen associated symptoms of genetic obesity.

As we mentioned earlier, Imcivree belongs to a class of medication called melanocortin 4 (MC4) receptor agonists and uses the active ingredient setmelanotide to facilitate weight loss. Setmelanotide is a small peptide drug that acts like a hormone and stimulates the MC4 receptor in the brain. 

The MC4 receptor is responsible for transmitting signals about hunger/fullness. It also manages the body's energy balance, glucose metabolism, blood pressure, heart rate, and body weight. Patients with genetic conditions or deficiencies typically have MC4 receptor mutations or issues with how this receptor/pathway works, causing them to feel continuously hungry and become severely obese.

Scientific evidence shows that even subtle changes in the melanocortin system can increase susceptibility to developing obesity. By stimulating this receptor, Imcivree stops the brain from sending out mixed signals regarding hunger and fullness. It instead reduces the unnecessary impulse to eat and manipulates the body into feeling fuller for longer. 

The product also regulates/increases normal and resting metabolism rates, helping the body burn adequate amounts of calories for energy at the right times and burn additional calories while resting, which together leads to significant weight loss. 

By using this approach, the drug ensures that users do not run the risk of experiencing adversities that come with other weight loss initiatives such as dieting. According to experts, some dieting methods can do more harm than good to those with obesity.

Studies have shown that diets that encourage food restriction are inappropriate for weight loss as they may lead to the opposite—weight gain and the development of eating disorders. This can be much more harmful to one's health than obesity.

The Safety and Efficacy of Imcivree 

When it comes to a concept like weight loss in the obese, caution must be taken as several underlying conditions, such as diabetes and high blood pressure, accompany obesity. In these circumstances, the drug used to induce weight loss must tick both safety and efficacy boxes. An extensive number of studies record the safety and efficacy of Imcivree that all come to the same conclusion—the drug is nothing short of excellent. 

The drug was designed to naturally trigger weight loss without affecting the body or the primary condition (obesity) or secondary conditions that might be present. Below we look at studies that demonstrate the drug's safety and efficacy:

  • A clinical trial published on PubMed showed the effects of setmelanotide in individuals with severe obesity due to POMC deficiency obesity or LEPR deficiency obesity. 45% of patients in the LEPR trial and 80% of the patients in the POMC trial achieved at least 10% weight loss in approximately 1 year. No serious treatment-related adverse events occurred in both trial.

  • Evidence from a study published in The Lancet confirmed the efficacy, safety, and tolerability of setmelanotide in a trial that involved patients with Bardet-Biedl syndrome. The participants reached at least a 10% reduction in body weight after 52 weeks of using setmelanotide. The most commonly reported adverse effects were mild hyperpigmentation and an injection site skin rash.

  • A clinical trial in the Journal of the Endocrine Society evaluated the effects of setmelanotide on individuals with POMC, PCSK1, and LEPR Deficiency. The results showed Setmelanotide was associated with reduced body weight and hunger scores in patients with POMC, PCSK1, and LEPR deficiency obesity. Mild adverse reactions, such as skin rashes, were noted in a small group of users.

The positive outcomes from these studies prove that Imcivree is indeed effective and does work to accelerate weight loss in obese individuals in a safe way. The drug is also well tolerated, with evidence showing that only a small number of patients experience mild side effects from use. 

The Bottom Line 

The complexity of obesity cases varies from person to person, and when other conditions like genetic mutations and deficiencies are added to the picture, it can make navigation to a successful outcome difficult. However, drugs such as Imcivree symbolize hope as scientific evidence proves its effectiveness in managing obesity. In a nutshell, Imcivree can:

  • Reduce hunger

  • Induce weight loss

  • increase resting energy metabolism 

  • Improve insulin and leptin sensitivity 

  • Increase the number of calories burnt 

  • help regulate and control energy balance

  • shift energy source to fat in obese individuals

Although not necessary, a beneficial diet and exercise plan combined with Imcivree use can foster better results. Opting for evidence-based dietary strategies such as the Metabolism Reset Diet can make fat elimination easier in adults. Paired with the Imcivree promise of no weight regain, the combination is a reliable long-term solution to obesity. All in all, the drug is an excellent choice for children and adults who have obesity caused by genetic conditions. 



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This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your physician about the risks and benefits of any treatment. Nu Image Medical may not offer the medications or services mentioned in this article.