Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr;24(6):667-674.
doi: 10.1080/14656566.2023.2199152. Epub 2023 Apr 6.

An evaluation of setmelanotide injection for chronic weight management in adult and pediatric patients with obesity due to Bardet-Biedl syndrome

Julia Lazareva  1 , Sheila M Brady  1 , Jack A Yanovski  1
Affiliations

An evaluation of setmelanotide injection for chronic weight management in adult and pediatric patients with obesity due to Bardet-Biedl syndrome

Julia Lazareva et al. Expert Opin Pharmacother. 2023 Apr.

Abstract

Introduction: Bardet-Biedl Syndrome (BBS) is a rare, multisystemic ciliopathy with an incidence of obesity of 89%. Mutations in genes encoding BBS proteins are linked to reduced leptin sensitivity of hypothalamic POMC neurons and reduced activation of the melanocortin-4 receptor (MC4R) pathway due to deficient α-MSH production by hypothalamic POMC neurons. The MC4R pathway is involved in controlling body weight and energy metabolism, and its disruption is linked to hyperphagia and obesity. Setmelanotide is an MC4R agonist that counteracts deficiencies in the MC4R pathway of individuals with BBS.

Areas covered: Data from clinical trials were reviewed along with information available from setmelanotide's approval for treatment of obesity in people ages ≥6y with a clinical diagnosis of BBS.

Expert opinion: Setmelanotide is available as a daily injectable that can be used for amelioration of obesity in people with Bardet-Biedl syndrome. Its cost is substantial, which may limit its use, but among those who respond, setmelanotide can reduce body mass dramatically and potentially improve comorbid conditions associated with obesity. Setmelanotide treatment has generally tolerable side effects, primarily injection site reactions and nausea/vomiting that generally improve with continued use; almost all people using setmelanotide experience marked skin darkening due to off-target activation of cutaneous MC1R.

Keywords: Bardet–Biedl syndrome; Obesity; melanocortin agonist; pharmacotherapy; setmelanotide.

PubMed Disclaimer

Conflict of interest statement

J A Yanovski reports grant support for clinical trials from Rhythm Pharmaceuticals, Inc. for use of setmelanotide in clinical trials including for Bardet Biedl Syndrome. J A Yanovski also reports grant support for unrelated pharmacotherapy research from Soleno Therapeutics, Inc., Versanis Bio, and Hikma Pharmaceuticals, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.. Melanocortin-4 receptor pathway with setmelanotide action.
BBSx represents the mutations in BBS proteins that disrupt leptin sensitivity in the pathway. Setmelanotide action later in the pathway potentially compensates for these genetic deficiencies by activating the MC4R.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • G protein-coupled receptors and obesity.
    Pocai A. Pocai A. Front Endocrinol (Lausanne). 2023 Dec 14;14:1301017. doi: 10.3389/fendo.2023.1301017. eCollection 2023. Front Endocrinol (Lausanne). 2023. PMID: 38161982 Free PMC article. Review.

References

    1. Beales PL, Elcioglu N, Woolf AS, et al. New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey. J Med Genet. 1999. Jun;36(6):437–46. - PMC - PubMed
    1. Green JS, Parfrey PS, Harnett JD, et al. The cardinal manifestations of Bardet-Biedl syndrome, a form of Laurence-Moon-Biedl syndrome. N Engl J Med. 1989. Oct 12;321(15):1002–9. - PubMed
    1. Feuillan PP, Ng D, Han JC, et al. Patients with Bardet-Biedl syndrome have hyperleptinemia suggestive of leptin resistance. J Clin Endocrinol Metab. 2011. Mar;96(3):E528–35. - PMC - PubMed
    1. Castro-Sanchez S, Alvarez-Satta M, Valverde D. Bardet-Biedl syndrome: A rare genetic disease. J Pediatr Genet. 2013. Jun;2(2):77–83. - PMC - PubMed
    1. Perea-Romero I, Solarat C, Blanco-Kelly F, et al. Allelic overload and its clinical modifier effect in Bardet-Biedl syndrome. NPJ Genom Med. 2022. Jul 14;7(1):41. - PMC - PubMed