New oral GLP-1 shows promise: Study

A once-daily oral GLP-1 receptor agonist, orforglipron, has shown greater improvements in type 2 diabetes management and weight loss than oral semaglutide, according to a new international study.
 
The ACHIEVE-3 study, sponsored by drug manufacturer Eli Lilly, compared its orforglipron (12 mg or 36 mg) with oral semaglutide (7 mg or 14 mg) in a head-to-head trial involving 1698 adults with type 2 diabetes.
 
Eli Lilly said it will use the study’s findings to support its application to the Therapeutic Goods Administration to register the drug for obesity management as well as type 2 diabetes.
 
Chair of RACGP Specific Interests Obesity Management, GP and dietitian, Dr Terri-Lynne South, said while she welcomes more ‘potential’ oral GLP-1 medication being available to Australian GPs and their patients, a separate study is needed to assess orforglipron’s effectiveness in treating obesity.
 
‘Because this particular study is just in regards to type two diabetes, we’d need to see a separate study around comments on obesity management,’ she told newsGP. 
 
‘In the real world it would likely be that a higher dose is needed for obesity management.’
 
The year-long randomised study assessed changes in blood sugar levels (HbA1c), body weight and cardiovascular risk factors such as cholesterol and blood pressure in the participants from the US, Argentina, China, Japan and Mexico.
 
All participants had type 2 diabetes poorly controlled by metformin, and all had BMIs above 25.
 
Those taking the once-daily orforglipron showed greater improvements in glycaemic control and more weight loss than those taking oral semaglutide.
 
However, while gastrointestinal adverse events were the most frequently reported adverse events across all groups, they were more frequent with those taking orforglipron, reported by 59% of participants on 12 mg and 58% on 36 mg, compared with 37% on semaglutide 7 mg and 45% on 14 mg.
 
Discontinuation due to adverse events was also higher with orforglipron at 9% (12 mg) and 10% (36 mg), versus 4% (7 mg) and 5% (14 mg) with semaglutide.
 
Dr South said it appears first-generation oral semaglutide was used in the study, as the doses are lower compared to those in second-generation medications such as Wegovy and Ozempic.
 
‘We do know that the differences between the first and the second-generation semaglutide made a big difference with regards to the gastrointestinal side effects,’ she said.
 
‘The second generation has better bioavailability and therefore they could get away with a lower dose for both diabetes as well as obesity management, and therefore a lower dose meant not as significant gastrointestinal side effects versus the first formulation.
 
‘If they’re applying to have it available for weight loss as well, and people need to take more of this medication, then the chances are that the gastrointestinal effects could be worse too.’
 
Although randomised, the trial was also ‘open label’, which Dr South said was significant, as participants could bring an ‘unconscious bias’ to the study by knowing which medication they were taking.
 
However, she still believes ‘the more options we have available, the better’ for oral GLP-1s in Australia.
 
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