Trial reportThe lancet. Diabetes & endocrinology2022
Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period.
Trial report in The lancet. Diabetes & endocrinology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT07674290 (Real-World Effectiveness, Safety and Patient-reported Outcomes of Setmelanotide in Patients With Bardet-Biedl Syndrome), which is not on this map. Cited by 114 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Real-World Effectiveness, Safety and Patient-reported Outcomes of Setmelanotide in Patients With Bardet-Biedl Syndrome: A Prospective Mono Centric Observational Interventional Study
Who cites it
114 citing papers in PubMed, 5 syntheses or guidelines pooled it, 170 citations in OpenAlex.
- A systematic literature review of economic evaluations of setmelanotide.European journal of clinical pharmacology · 2026Pooled it
- Multidimensional Characterisation of Eating Behaviour in Genetic Obesity: A Systematic Review.Obesity facts · 2026Pooled it
- Hyperphagia in rare melanocortin-4 receptor pathway diseases: therapeutic options and assessing treatment response.Reviews in endocrine & metabolic disorders · 2025Pooled it
- Guideline
- Pharmacotherapy for obesity management in adults: 2025 clinical practice guideline update.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2025Guideline
- Setmelanotide in Bardet-Biedl Syndrome: A 52-Week Comparison of Phase 3 Trial Participants With a Matched Registry Cohort.Obesity (Silver Spring, Md.) · 2026Trial
- Quality of life improvements with setmelanotide treatment in acquired hypothalamic obesity: TRANSCEND trial interview results from US participants.Frontiers in behavioral neuroscience · 2026Trial
- Impact of Setmelanotide on Metabolic Syndrome Risk in Patients With Bardet-Biedl Syndrome.The Journal of clinical endocrinology and metabolism · 2025Trial
- Quality of life improvements following one year of setmelanotide in children and adult patients with Bardet-Biedl syndrome: phase 3 trial results.Orphanet journal of rare diseases · 2023Trial
- Synthetic strategies and therapeutic insights into FDA-approved indole-containing drugs.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Measuring Hunger Severity in Rare MC4R Pathway Diseases: Development and Psychometric Evaluation of the Most Hunger Item.Advances in therapy · 2026Article
- Safety and effectiveness of setmelanotide in young patients with severe obesity due to craniopharyngioma: a real world monocentric experience.Journal of endocrinological investigation · 2026Article
- IMPROVE 2025: The 3rd International Meeting on Pathway-Related Obesity: Vision & Evidence.Clinical obesity · 2026Article
- Shared and distinct genetic architectures of eating disorders and obesity: From monogenic causes to polygenic risk.Reviews in endocrine & metabolic disorders · 2026Review
- Primary cilia: master conductors of cellular communication in development and disease.Nature reviews. Nephrology · 2026Review
- Anti-obesity medications impacting the eye: An emerging concern - a narrative review.World journal of methodology · 2026Review
- Current and forthcoming pharmacotherapies for adolescent obesity: Evidence-based review.World journal of clinical pediatrics · 2026Review
- Setmelanotide Response Variability in Two Genetically Confirmed Pediatric Kidney Transplant Recipients with Bardet-Biedl Syndrome.International journal of molecular sciences · 2026Article
- Rationale of renewed efforts in developing MC4R modulators to treat metabolic disorders.Acta pharmaceutica Sinica. B · 2026Review
- Genetic determinants of obesity: mechanisms, clinical implications, and targeted therapies.Endocrine · 2026Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundImpaired cilial signalling in the melanocortin-4 receptor (MC4R) pathway might contribute to obesity in patients with Bardet-Biedl syndrome and Alström syndrome, rare genetic diseases associated with hyperphagia and early-onset severe obesity. We aimed to evaluate the effect of setmelanotide on bodyweight in these patients.
methodsThis multicentre, randomised, 14-week double-blind, placebo-controlled, phase 3 trial followed by a 52-week open-label period, was performed at 12 sites (hospitals, clinics, and universities) in the USA, Canada, the UK, France, and Spain. Patients aged 6 years or older were included if they had a clinical diagnosis of Bardet-Biedl syndrome or Alström syndrome and obesity (defined as BMI >97th percentile for age and sex for those aged 6-15 years and ≥30 kg/m
findingsBetween Dec 10, 2018, and Nov 25, 2019, 38 patients were enrolled and randomly assigned to receive setmelanotide (n=19) or placebo (n=19; 16 with Bardet-Biedl syndrome and three with Alström syndrome in each group). In terms of the primary endpoint, 32·3% (95% CI 16·7 to 51·4; p=0·0006) of patients aged 12 years or older with Bardet-Biedl syndrome reached at least a 10% reduction in bodyweight after 52 weeks of setmelanotide. The most commonly reported treatment-emergent adverse events were skin hyperpigmentation (23 [61%] of 38) and injection site erythema (18 [48%]). Two patients had four serious adverse events (blindness, anaphylactic reaction, and suicidal ideation); none were considered related to setmelanotide treatment.
interpretationSetmelanotide resulted in significant bodyweight reductions in patients with Bardet-Biedl syndrome; however, these results were inconclusive in patients with Alström syndrome. These results support the use of setmelanotide and provided the necessary evidence for approval of this drug as the first treatment for obesity in patients with Bardet-Biedl syndrome.
fundingRhythm Pharmaceuticals.
Indexed as
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.