A daily pill appears to lower blood sugar in people with type 2 diabetes as effectively as injectable drugs like Ozempic and Mounjaro. The medication, called orforglipron, also led to substantial weight loss in clinical trials, meaning it could become a convenient alternative to popular weight-loss drugs.
Drugs mimicking the hormone GLP-1, which regulates appetite and blood sugar, have exploded in popularity. Known as GLP-1 agonists, these medications can treat obesity, type 2 diabetes and heart disease. One downside is that nearly all of them must be injected, making them inconvenient and uncomfortable as well as difficult to transport, as they must be refrigerated.
Pharmaceutical companies have been racing to produce pill-based versions of these medications. Orforglipron, developed by the US drug maker Lilly, is the first to successfully complete a phase III clinical trial – the final step before a drug is submitted to regulatory agencies for review. Similar to Ozempic and Wegovy, orforglipron binds to GLP-1 receptors in the body, but unlike other GLP-1 agonists, it can be taken as a daily pill.
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“This oral formulation could help remove a significant barrier for patients who find injections challenging or undesirable,” says at NYU Langone Health in New York. It could also make people more willing to start treatment and stick with it, she says.
Phase III trial results announced by Lilly on indicate orforglipron is comparable to other GLP-1 agonists in terms of safety and efficacy. The study involved 559 adults in the US, China, India, Japan and Mexico, all of whom had type 2 diabetes that couldn’t be managed with diet and exercise alone. Participants received either a placebo or a 3-milligram, 12-milligram or 36-milligram dose of orforglipron.
After 40 weeks, those taking orforglipron saw their A1C levels – a measure of average blood sugar over the past three months – decline by 1.3 to 1.6 per cent. In comparison, A1C levels fell by only 0.1 per cent, on average, in participants given a placebo. Among participants taking the highest orforglipron dose, more than 65 per cent achieved an A1C of 6.5 per cent or less, which is below the threshold that signals someone has diabetes.
Still, these results are similar to those seen with Ozempic. In clinical trials, people with type 2 diabetes taking the highest dose of Ozempic saw A1C levels fall by , on average. But they were also taking other diabetes medications, whereas participants in the orforglipron trial weren’t. Direct comparisons between orforglipron and other GLP-1 agonists require head-to-head trials, says a Lilly spokesperson.
Orforglipron causes similar side effects to those seen with other GLP-1 agonists, such as diarrhoea, nausea and indigestion. The drug didn’t affect liver function, which was a concern given that another oral GLP-1 agonist, called danuglipron, led to liver damage in one clinical trial participant. As a result, the drug’s maker, US pharmaceutical company Pfizer, announced on that it would halt clinical trials and stop developing the drug. Pfizer did not respond to żěè¶ĚĘÓƵ’s request for comment.
Orforglipron also led to substantial weight loss: those taking the highest dose lost 7.9 per cent of their body weight, on average. This is far lower than that seen with semaglutide, the drug in medications like Ozempic and Wegovy. In clinical trials, 40 weeks of semaglutide treatment led to a roughly in body weight in people who were overweight or had obesity.
However, the latest orforglipron trial was designed to evaluate the medication in people with type 2 diabetes, not those with obesity, says a Lilly spokesperson. A phase III trial is currently under way in people who are overweight or have obesity, and results are expected later this year, says the spokesperson. Lilly expects to submit the drug to regulatory agencies as a weight-loss therapy by the end of this year and as a treatment for type 2 diabetes in 2026.
If approved, orforglipron could substantially expand weight-loss treatment, says Jaisinghani. Because it is a pill, it may be easier to produce, “which could help lower overall costs – an important consideration in expanding equitable access to obesity care”, she says. Lilly declined to comment on the drug’s cost, given it is still undergoing clinical trials.
