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The Lancet: New weight loss pill leads to greater blood sugar control and weight loss for people with diabetes than current oral GLP-1, phase 3 trial finds
A novel GLP-1 receptor agonist (RA) pill called orforglipron leads to a larger reduction in blood sugar levels after a year than the current available oral GLP-1 RA (semaglutide), finds a phase 3 randomised controlled trial published in The Lancet. Additionally, participants taking orforglipron had significantly greater reductions in body weight than those taking oral semaglutide.
Currently the only available oral GLP-1 RA is semaglutide which must be taken on an empty stomach. Orforglipron is an alternative oral GLP-1 RA that can be taken with or without food and is currently under review with the FDA. ACHIEVE-3 is the first phase 3 trial to directly compare orforglipron (12 or 36 mg) with oral semaglutide (7 or 14 mg).
In the trial, over 1,500 people with type 2 diabetes from 131 medical research centres and hospitals in Argentina, China, Japan, Mexico, and the USA were randomised to take orforglipron at one of the two doses or semaglutide at one of two doses for a year.
The participants who took orforglipron had, on average, a greater drop in blood sugar levels for both doses than either of the doses of semaglutide. Patients, starting at an average weight of 97kg, lost on average 6-8% of their weight with orforglipron and 4-5% with semaglutide. However, 9-10% of participants in the orforglipron groups stopped taking the pill due to adverse events (mostly gastrointestinal issues), compared to 4-5% in the semaglutide groups.
Authors say that orforglipron could be a new treatment option for people with type 2 diabetes who prefer a pill to an injection and do not want any restrictions on food and fluid intake.
Expert Reaction
These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.
Professor Michael Horowitz is a Professor of Medicine and Director of the Centre of Research Excellence in Translating Nutrition to Good Health at Adelaide University. He is one of the authors of an editorial on this research, also published in The Lancet
"This drug is currently in development but is clearly a promising alternative to other treatments used to treat diabetes and obesity, such as semaglutide (Ozempic) injections and oral semaglutide.
While these are certainly promising results, the drug isn’t without side effects. It was less well-tolerated among participants, with more gastrointestinal adverse effects, such as nausea, reported than with semaglutide.
It’s not necessarily a replacement for current medications but provides an alternative for individuals who would prefer an oral therapy and have a high tolerance to potential side effects.”
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