DG FotoStock/Shutterstock.com
Novel weight-loss pill orforglipron (Emgality; Eli Lilly) offers patients with type 2 diabetes mellitus (T2DM) better blood sugar control and more weight loss than semaglutide — the only other GLP-1 receptor agonist pill currently available — according to the results of a phase III clinical trial.
Publishing the findings of the ‘ACHIEVE-3‘ study in The Lancet on 26 February 2026, researchers also found that more patients stopped taking orforglipron owing to adverse effects.
The team analysed data from 1,698 people with T2DM from 131 medical research centres and hospitals in Argentina, China, Japan, Mexico and the United States who were given either orforglipron or semaglutide daily for one year.
With an average starting weight of 97kg, patients taking orforglipron lost an average of 6–8% bodyweight, while those taking semaglutide lost an average of 4–5%, the study found.
In terms of blood sugar, the results showed that patients taking orforglipron 12mg experienced an average 1.7% reduction in HbA1c levels and a 1.9% reduction on the 36mg dose, whereas in the semaglutide groups, those taking 7mg and 14mg achieved a 1.2% and 1.5% reduction, respectively.
However, around twice as many patients in the orforglipron groups stopped taking the pill owing to adverse events, compared with the semaglutide groups, the study revealed. One in ten (9–10%) of patients who took orforglipron stopped taking the drug compared with 4–5% of patients who took semaglutide.
The study also showed that adverse events were reported by 75% (n=314) of 424 participants who received orforglipron 12mg, 75% (n=318) of 423 participants who received orforglipron 36mg, 71% (n=303) of 426 participants who received semaglutide 7mg and 72% (n=308) of 425 participants who received semaglutide 14mg.
More than half of patients who took orforglipron experienced gastrointestinal side effects (59% of those who received orforglipron 12mg and 58% of those who received orforglipron 36mg), compared with 37% of patients who took semaglutide 7mg and 45% of those who took semaglutide 14mg, the study results revealed.
A previous study of patients without T2DM, published in September 2025, revealed that those who took orforglipron 6mg as an adjunct to healthy diet and physical activity lost an average of 7.5% of their body weight over 72 weeks.
In the earlier ‘ATTAIN-1 trial‘, average weight loss increased with higher doses. The trial results showed 8.4% weight loss with orforglipron 12mg and 11.2% weight loss with orforglipron 36mg, compared with 2.1% weight loss with placebo.
Orforglipron is currently being appraised by the National Institute for Health and Care Excellence, with a decision on NHS use in England and Wales expected in 2026.
In October 2025, experts told The Pharmaceutical Journal that oral GLP-1s could offer patients greater choice and accessibility than injectable formulations.
Oral semaglutide is currently available in the UK for patients with T2DM as Rybelsus (Novo Nordisk). It must be taken in a fasted state in the morning, with no more than 120mL of water and at least 30 minutes before food, beverages or other oral medication.
Orforglipron can be taken with or without food.
