Eli Lilly's Oral Orforglipron Outperforms Semaglutide in Type 2 Diabetes Trial

A new oral medication developed by Eli Lilly could help patients lose more weight than by taking the active ingredient used in weight loss pills, according to results from a clinical trial. The drug, called orforglipron, is a GLP-1 agonist that targets the same appetite receptors as medications such as Mounjaro, Wegovy and Ozempic, but is taken in tablet form rather than administered via injection.

In a trial of over 1,500 patients from Argentina, China, Japan, Mexico and the US, patients who took orforglipron for a year experienced a greater drop in blood sugar levels and lost more weight than those on semaglutide. Orforglipron has been developed to treat both type 2 diabetes and obesity.

In the study, 1,698 participants were randomly assigned to receive either orforglipron, at a dose of 12mg or 36mg, or oral semaglutide, at 7mg or 14mg. Participants took their medication every day for a year, starting on a lower dose and increasing every four weeks until reaching their randomly assigned dose.

Results showed that both doses of orforglipron were better than that of semaglutide in reducing blood glucose levels, and they also lost more weight. Up to 43 per cent of participants on orforglipron were able to drop at least 10 per cent body weight, while only 21 per cent of those on semaglutide dropped enough weight to slash their risk of heart complications.

Patients with type 2 diabetes are recommended to lose between 5-15 per cent body weight to help manage their condition, with a more than 10 per cent reduction having disease-modifying effects including potential remission. Around a quarter of patients taking orforglipron managed to reach near-normal blood sugar levels during the course of the study whilst only around 12 per cent of those on semaglutide managed to reduce their blood sugar to safe levels.

The difference in blood sugar control was already significant after just a month of treatment and was sustained until the end of the trial. The results were particularly strong for patients with higher blood sugar levels at the start of the trial.

Orforglipron can also be taken with food, making it much more convenient than semaglutide, which needs to be taken on an empty stomach. However, the weight loss seen among people taking orforglipron was not as extreme as results seen in patients taking Mounjaro, which contains the active ingredient tirzepatide.

Writing in medical journal The Lancet, the authors said: "Our results suggest that orforglipron represents an important advancement in the oral treatment landscape for type2 diabetes. It's efficacy, safety, tolerability, and simple doing could address important barriers associated with current therapies, offering a new highly efficacious and safe option for individuals seeking glycemic and weight control with the use of injections."

The researchers concluded: "Orforglipron represents meaningful improvements in glycemic control and weight reduction compared with oral semaglutide in patients with type 2 diabetes, and with larger improvements in cardiometabolic risk factors and simplified administration."

However, during the course of the study around 10 per cent of participants on orforglipron had to stop taking the pill due to adverse reactions, such as gastrointestinal issues. Only 5 per cent of patients taking semaglutide experienced similar adverse reactions.

If approved, orforglipron could become the next GLP-1 drug approved for weight management. Two in three Britons are now overweight or obese, driving a nearly 40 per cent rise in type 2 diabetes among under 40s.