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.
The Lancet
Randomized controlled/clinical trial
People
Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial
See paper