A new daily pill could offer a more effective oral GLP-1 option for weight loss, according to a clinical trial that may open the door to an improved non-injection alternative to Wegovy and Mounjaro.
The drug, orforglipron, manufactured by Eli Lilly and prescribed for type 2 diabetes, targets the same GLP-1 receptors as oral semaglutide.
Like semaglutide, it lowers blood sugar levels, slows digestion and suppresses appetite, though it differs in one notable respect: it does not need to be taken on an empty stomach.
Orforglipron has not yet been approved by regulators in the UK, the US or Europe, though the US Food and Drug Administration is currently reviewing it.
Professor Naveed Sattar, professor of cardiometabolic medicine at the University of Glasgow, said: “The more effective oral medicines we have to help people with type 2 diabetes lose weight and keep it off, the better.”
He added that holistic approaches targeting weight, blood sugar and cardiovascular risk simultaneously were likely to deliver the greatest benefits, and that incretin-based therapies associated with substantial intentional weight loss “may well become first-line treatments for type 2 diabetes within the next decade, potentially helping many people achieve remission for several years.”
Semaglutide remains the only GLP-1 medication for type 2 diabetes available in pill form in the US, sold under the brand name Rybelsus for diabetes management.
A weight-loss pill version of Wegovy has also recently received approval, though oral semaglutide has consistently been shown to be less effective for weight loss than its injectable counterparts, such as Ozempic and Wegovy, or tirzepatide injections including Mounjaro.
Tablet versions of these drugs are widely regarded as potentially transformative, being easier to take and store and likely to prove cheaper in the long run.
Results from the first phase 3 trial to compare orforglipron directly with oral semaglutide found that patients with diabetes lost an average of six to eight per cent of their body weight on orforglipron, against four to five per cent on semaglutide.
The Achieve-3 trial, funded by Eli Lilly, followed more than 1,500 adults with type 2 diabetes across 131 medical research centres and hospitals in Argentina, China, Japan, Mexico and the US over the course of a year.
Participants received either 12mg or 36mg of orforglipron, or 7mg or 14mg of oral semaglutide.
Beyond the greater weight loss, participants taking either dose of orforglipron recorded lower average blood sugar levels at the end of the trial than those on either dose of semaglutide.
There were, however, some concerns.
Discontinuation rates were higher among those taking orforglipron, with around nine to ten per cent of participants stopping treatment because of side effects, primarily gastrointestinal complaints, compared with four to five per cent in the semaglutide groups.
Tam Fry, chair of the National Obesity Forum, welcomed the findings.
“Orforglipron could prove itself as the treatment of choice for the very obese diabetic,” he said.
“Its real bonus is in its straightforward use. When it is finally released, its availability must be more strictly controlled than semaglutide to avoid similar life-threatening usage.”
Dr Marie Spreckley of the MRC Epidemiology Unit at the University of Cambridge urged caution, noting that the higher discontinuation rates owing to adverse events, particularly gastrointestinal symptoms, “may have implications for tolerability and adherence in real-world settings.”
She also pointed out that the trial’s one-year duration left important questions about longer-term safety, cardiovascular outcomes and sustained effectiveness unanswered.
