Is the first GLP–1 pill around the corner?

An experimental GLP–1pill helped patients with type 2 diabetes significantly lower their blood glucose level and weight, according to newly released trial results.
 
Research published in the New England Journal of Medicine (NEJM), shows that over a 40-week trial participants taking orforglipron reduced their glycated haemoglobin levels ‘significantly’ more than those on a placebo.

It also found patients taking the highest dose of the oral GLP-1 agonist, which is currently in development for type 2 diabetes and weight management treatment, lost an average of 7.6% of their body weight.
 
According to Reuters, the weight loss data compares favourably with semaglutide (sold as Ozempic), with trials for that injectable treatment showing patients living with diabetes lost around 6% of their body weight on the highest dose.
 
Orforglipron also reportedly has a simpler production process than injected GLP-1 drugs such as Ozempic and tirzepatide (sold as Mounjaro) and does not require cold storage – factors that could help improve access to the drug if it is approved for use.
 
Manufacturer Eli Lilly says it now plans to share the results with the Therapeutic Goods Administration in a bid to make orforglipron available for Australians living with type 2 diabetes.
 
Dr Gary Deed, Chair of RACGP Specific Interests Diabetes, said the trial is ‘an interesting study’.
 
‘It confirms that oral GLP-1RAs are effective in lowering glucose,’ he told newsGP.
 
He noted that while the study was relatively short term, ‘the effect was clear’ and said the once-daily pill could be ‘particularly attractive as an option for people living with diabetes not wanting injectable therapy’.
 
According to Eli Lilly, orforglipron is the first oral GLP-1 agonist, taken without food and water restrictions, to complete a phase 3 trial.
 
The drug was used in a double-blind, randomised, placebo-controlled trial including 526 adult participants with type 2 diabetes across China, India, Japan, Mexico, and the United States.
 
Randomly assigned groups received one of three doses – 3 mg, 12 mg, 36 mg – or a placebo once a day for 40 weeks.
 
Groups started on a dose of 1 mg of the medication, which can be taken without food and water restrictions, and their dosage was increased every four weeks until they reached their assigned level.
 
Eligible participants included those with early type 2 diabetes who were only being treated using diet and exercise and had a glycated haemoglobin level of between 7% and 9.5%, as well as a body mass index of at least 23.
 
The NEJM authors reported the most common side effects as ‘mild-to-moderate gastrointestinal events’, with the trial discontinued due to adverse events in 4.4% to 7.8% of participants receiving orforglipron compared to 1.4% given the placebo.
 
‘No episodes of severe hypoglycaemia were reported,’ the authors wrote.
 
The majority of participants (61.7%) had not previously received glucose-lowering medications. 
 
The trial results showed by those on the lowest dose cut their glycated haemoglobin level by an average of 1.24 percentage points compared to 1.47 percentage points with the 12-mg dose, and 1.48 percentage points on the 36-mg dose. That compared to a mean reduction of 0.41 percentage points for those on the placebo.
 
Those on the 3-mg dose lost an average of 4.5% of their bodyweight, rising to 5.8% with the 12-mg dose group, and 7.6% for the 36-mg dose compared to a 1.7% reduction for the placebo group.
 
‘It seems that 12 mg is possibly the ideal glycaemic lowering dose, but weight loss continued beyond that dose,’ Dr Deed said.
 
He also observed that as the pill was used among patients with early onset diabetes without other clinical agents such as metformin, there was potential for even greater glycaemic lowering.
 
‘These clinically meaningful findings will accelerate the momentum generated by the research and real-world use of injectable medicines that activate key hormones to regulate blood sugar and appetite,’ said Tori Brown, General Manager of Eli Lilly Australia and New Zealand.
 
Dr Deed noted that given the short time frame of the trial ‘longer term data is needed to ensure clinical uptake can be applied safely’.
 
A spokesperson for Eli Lilly confirmed that trials for the drug for obesity treatment and other metabolic conditions for patients without diabetes are also being conducted.
 
A number of other experimental GLP-1 pills are also in clinical development but are at an earlier stage.
 
Log in below to join the conversation.
 

diabetes GLP-1 orforglipron weight loss