Clinical Trials and Treatments
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GLP-1/GIP/Glucagon receptor agonists and analogues| Metreleptin| IMCIVREE| Clinical Trials| Emanate|
Links to Useful papers on Anti-Obesity medication can be found in Professionals section >Library.
GLP-1/GIP/Glucagon receptor agonists and analogues
Glucagon-like peptide-1 (GLP-1) receptor agonists and analogues are a new class of medications that are transforming the treatment of people with obesity.
Liraglutide (Saxenda) and Semaglutide (Ozempic for type 2 diabetes, Wegovy for obesity) work by stimulating brain receptors for GLP-1 which play an important role in the central regulation of appetite and body weight. GLP-1 also acts as an incretin hormone to stimulate insulin release after meals, thereby justifying its use in the treatment of type 2 diabetes.
Some drugs also target brain-expressed receptors for another incretin, glucose-dependent insulinotropic polypeptide (GIP). These drugs are called dual agonists. Some drugs target GLP-1, GIP and glucagon receptors – they are called triple receptor agonists.
Two GLP-1 receptor agonists (GLP-1RAs) are currently licensed in the UK for the treatment of obesity:
- Liraglutide (Saxenda), as daily subcutaneous injection
- Semaglutide (Wegovy), as weekly subcutaneous injection
Both have shown high efficacy in reducing body weight for patients with obesity, leading to an average weight loss of 5-10% with Liraglutide and 10-17% with Semaglutide across various clinical trials (library).
Evidence from the SELECT trial of Semaglutide indicates a reduction in major adverse cardiovascular events (including death from cardiovascular causes, nonfatal myocardial infarction and nonfatal stroke) of 20% in people with overweight and obesity (BMI of 27 or greater) and pre-existing cardiovascular disease, without diabetes, after a mean of 2.7 years of treatment.
The STEP-TEENS trial has demonstrated the efficacy of Semaglutide in adolescents aged 12-17 years
Tirzepatide (Mounjaro) a, dual GLP-1 and GIP receptor agonist, induced a weight loss of up to 20.9% in a phase-3 clinical trial. It has been licensed for the treatment of type 2 diabetes (October 2023) and is expected to be licensed in the UK soon for the treatment of obesity.
When coupled with intensive advice on diet and exercise (which led to 5% weight loss), Tirzepatide leads to an additional 21% weight loss.
Other medications have shown promising results in phase-2 clinical trials. These include the oral GLP-1 receptor agonist Orforglipron (9-13% weight loss at 26 weeks) and Retatrutide, a triple GLP-1, GIP and Glucagon receptor agonist (up to 24% weight loss at 48 weeks).
Based on the evidence currently available and our clinical experience, these medications are likely to be effective for patients with heterozygous MC4R deficiency (the most common form of genetic obesity) and probably for other forms of genetic obesity.
Their main side effects are gastrointestinal (nausea, vomiting, diarrhoea and abdominal pain). These are usually dose-dependent and mild to moderate in intensity.
Currently, Liraglutide and Semaglutide can only be prescribed by physicians in Tier-3 obesity clinics for patients with obesity (BMI >35 kg/m2) and at least one co-morbidity. Patients from some ethnic minority backgrounds can be treated at lower BMI levels.
At present, access to these medications is currently limited by long waiting lists for specialist obesity services across the UK, as well as supply shortages (medications and pen devices).
Some government and local initiatives are testing whether patients can receive treatment from their GPs but this is not available in most towns. Some anti- obesity medications (AOM’s) are available through private clinics where a healthcare professional qualified to prescribe medicines can provide a prescription which can then be prepared by a local pharmacy.
Patients should be advised to take great care obtaining medication through the internet as fake medication and fake pen devices are being sold.
Metreleptin
Metreleptin/Myalept is licensed for the treatment of congenital leptin deficiency (severe obesity due to homozygous mutations in the LEP gene) and is only available to be prescribed by Prof Farooqi in the UK. All patients will need to have a formal genetic diagnosis confirmed in the NHS reference laboratory based at Addenbrooke’s Hospital, Cambridge before they are considered for treatment. If you would like to refer a patient for treatment, please contact Prof Farooqi via This email address is being protected from spambots. You need JavaScript enabled to view it.. Patients will also remain under the care of the referring Consultant given their complex needs.
IMCIVREE
In October 2022, Setmelanotide (IMCIVREE), a Melanocortin 4 receptor (MC4R) agonist, was licensed by the NHS for the chronic weight management of patients more than 6 years of age with three genetic obesity syndromes (homozygous or compound heterozygous POMC, PCSK1 and LEPR deficiency).
Prof Farooqi is the only UK Physician able to prescribe IMCIVREE. If you have a patient with one of these conditions, please contact Prof Farooqi via This email address is being protected from spambots. You need JavaScript enabled to view it.. All patients will need to have a formal genetic diagnosis confirmed in the NHS reference laboratory based at Addenbrooke’s Hospital, Cambridge before they are considered for treatment. Patients will also remain under the care of the referring Consultant given their complex needs.
Clinical Trials
We are currently running a number of Phase 2/3 clinical trials of Setmelanotide, a Melanocortin 4 receptor (MC4R) agonist in Cambridge. These trials are/will be running at other sites in the UK. We can connect you to the site that may be most accessible for your patients.
Please see below for details of each trial and which patient groups are currently eligible for recruitment. If you have identified a patient with a variant in an obesity gene included in these trials, and if your patient is interested in participating in such studies, please let us know, via This email address is being protected from spambots. You need JavaScript enabled to view it..
Emanate
Emanate is a Phase 3 trial of Setmelanotide in patients aged 6 to 65 years of age with the following genetic variants:
- Heterozygous pathogenic, likely pathogenic or variant of uncertain significance suspected to be pathogenic (VOUS-SP) variants in POMC
- Heterozygous pathogenic, likely pathogenic or variant of uncertain significance suspected to be pathogenic (VOUS-SP) variants in PCSK1
- Heterozygous pathogenic, likely pathogenic or variant of uncertain significance suspected to be pathogenic (VOUS-SP) variants in LEPR
- Homozygous, heterozygous, or compound heterozygous variants in SH2B1. Pathogenic, likely pathogenic and variants of uncertain significance are all eligible for inclusion.
- Chromosome 16p11.2 deletions encompassing SH2B1
- Homozygous, heterozygous, or compound heterozygous variants in SRC-1. Pathogenic, likely pathogenic and variants of uncertain significance are all eligible for inclusion.
Further details can be found here.
