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Scientists comment on the Medicines and Healthcare products Regulatory Agency (MHRA) authorising the orforglipron obesity pill.
Dr Marie Spreckley, research programme manager and researcher, Prevention of Diabetes and Related Metabolic Disorders in High Risk Groups, University of Cambridge, said:
“Today’s authorisation is an important development because orforglipron offers GLP-1 treatment as a once-daily tablet that can be taken without food or water restrictions, providing an alternative for people who may prefer not to use injections.
“The phase 3 evidence is convincing that orforglipron can support meaningful weight loss and improve blood glucose control. In the 72-week ATTAIN-1 trial, adults with obesity and without diabetes lost an average of 7.5% to 11.2% of their body weight across the three doses studied, compared with 2.1% among those receiving placebo.
“The pivotal obesity trial compared orforglipron with placebo rather than injectable semaglutide or tirzepatide, so it cannot tell us directly how these treatments compare for weight management. A separate head-to-head trial in people with type 2 diabetes found greater reductions in blood glucose and body weight with orforglipron than with the doses of oral semaglutide tested.
“The most common adverse events were gastrointestinal, including nausea, constipation, diarrhoea and vomiting, and were generally mild to moderate. However, adverse events led more participants to discontinue orforglipron than placebo, particularly at higher doses.
“As with any newly authorised medicine, longer-term and real-world evidence will be important for understanding its effectiveness and safety, and how well people tolerate and continue taking it in routine care.
“MHRA authorisation does not mean that orforglipron will immediately become available through the NHS. It is not currently available through the NHS, and decisions about its use will follow established processes, including an assessment of its clinical and cost effectiveness by NICE.”
Dr Simon Cork, Senior Lecturer in Physiology, Anglia Ruskin University, said:
“The announcement of the licensing of orforglipron for weight management is a big step forward in the treatment of obesity for a few reasons.
“Firstly, this medication is being authorised for people at lower body weights than other weight loss medications. Whilst more detail is required to understand the full scope of who will be eligible, a BMI of 30 means this will likely be available to more people.
“Additionally, whilst we still await details on cost, this drug is likely to be much cheaper than currently available medications. Pill medications are much cheaper to manufacture than injectable medications, and the nature of the active compound in this medication is much cheaper to make than those found in injectable medications or in oral Wegovy. In the US where orforglipron is already authorised for weight loss, a monthly prescription costs $149-$349 depending on dosage, compared with over $1000 for injectable Wegovy.
“Whilst the weight loss experienced on orforglipron is typically lower than that experienced with injectable medications, patients can still expect to see significant, clinically meaningful changes to their weight.
“Of interest, a recent clinical trial (ATTAIN-MAINTAIN) found that patients who lost weight through injectable medications (semaglutide or tirzepatide) were able to then sustain a higher proportion of that weight loss through orforglipron than those who received a placebo, providing a much more economically viable option for long-term weight management using GLP-1 based weight loss medications.”
Prof Naveed Sattar, Professor of Cardiometabolic Medicine/Honorary Consultant, University of Glasgow, said:
“This is good news for people living with obesity. Having another oral treatment option expands choice, particularly for individuals who are reluctant to use injectable medicines or who may not require the degree of weight loss typically achieved with the most effective injections.
“One advantage of orforglipron is its convenience. Unlike oral semaglutide, which must be taken fasting before food, it can be taken at any time of day, making treatment simpler for some people.
“That said, oral semaglutide appears to deliver somewhat greater weight loss and, importantly, has proven cardiovascular benefits. While similar outcome data are not yet available for orforglipron, the medicine has been shown to produce clinically meaningful weight loss and improvements in several cardiovascular risk factors. Overall, the arrival of another effective oral option is a positive development and should help more people access treatment that best suits their needs and preferences. However, the overall direction of travel is encouraging: we are seeing a growing range of effective medicines that should help more people living with obesity achieve and maintain meaningful weight loss and, hopefully, improve their long-term health.”
Declared interests
Dr Marie Spreckley: “Dr Marie Spreckley is a postdoctoral researcher at IMS Epidemiology, University of Cambridge, where her research focuses on obesity, nutrition and incretin-based therapies. Her research has received no industry funding, and she has no personal financial interests, consultancy roles, advisory positions, speaker fees, stock ownership, or honoraria from manufacturers of GLP-1 or GIP/GLP-1 receptor agonists.”
Dr Simon Cork: “No CoI to declare.”
Prof Naveed Sattar: “NS has consulted for and/or received speaker honoraria from Abbott Laboratories, AbbVie, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gan & Lee, GlaxoSmithKline, Hanmi Pharmaceuticals, Janssen, Kailera, Mass Medicines, Menarini-Ricerche, Merck Sharp & Dohme, Metsera, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche, Sanofi, UCB Pharma and Verdiva Bio; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche.He does not hold any stocks or shares in any medical companies. He is Chair of the Obesity Healthcare Goals Programme for Office for Life Sciences, HM Government.”