Roll Call In The Oral GLP-1 Race
By Katie Anderson, Chief Editor, Pharmaceutical Online
The market for GLP-1 agonists is booming and expected to only get bigger. As rates for obesity and cardiovascular disease increase, so too does the demand for GLP-1 drugs. Matter of fact, the global market is currently valued at $53.46 billion and expected to grow 17.46% to reach $156.71 billion in 2030.1
GLP-1 drugs are having a heyday, but as Bret Michaels sings, “every rose has its thorn.” Indeed, injectable GLP-1 drugs are difficult to make and use and treatment is costly for many patients. Not to mention, patent cliffs for injectable GLP-1 agonists are looming, and there are still always going to be those patients who are uncomfortable with the injection delivery. Enter the race for an effective oral GLP-1 agonist, where some players entered with good old-fashioned R&D and others partnered and acquired to enter the competition. So, who has the Goldilocks of oral GLP-1 agonists? No one yet, but there are some formidable players. Let’s jump in.
Challenges for Oral Versions
Before we get in to the major players in the space, it is important to acknowledge the challenges they face in developing an oral GLP-1 agonist. Unlike injectables, which go directly into the bloodstream, oral drugs have to pass through the gastrointestinal system first. Not only does it make them less bioavailable, but they often come with gastrointestinal side effects such as stomach pain, diarrhea and vomiting.
To achieve weight loss efficacy with oral GLP-1 drugs, higher concentrations are needed as well as absorption enhancers. Though many are close to the finish line with efficacy and oral delivery, one that eliminates the gastro side-effects has yet to be seen.
First To The Line: Novo
Novo Nordisk beat its competitors to the punch with the approval of an oral semaglutide (Rybelsus) in late 2019 for the treatment of type 2 diabetes. However, this oral GLP-1 agonist has its drawbacks—it has strict guidelines on administration (empty stomach with little water). Patients have reported gastrointestinal side effects such as nausea, vomiting and abdominal pain.
Rybelsus is not approved for the treatment of obesity or weight loss. Because of oral administration, a higher dosage would be needed for weight loss. The company tested both 25 and 50 mg doses of oral Wegovy and submitted an NDA in May 2025 for the 25 mg version. Clinical trails on the 25mg version saw an average of 16.6% weight loss, with mild to moderate gastrointestinal side effects such as vomiting and nausea.
Partnerships/Acquisitions In Oral Obesity Drugs
Pfizer has taken a few stabs at developing an oral GLP-1 agonist. Although danuglipron showed good weight loss in phase II trials, the drug was discontinued when a trial participant suffered liver damage. Prior to danuglipron, it had already scrapped lotigripron in clinical trials because of elevated liver enzymes. Pfizer is back in the game recently with its Metasera acquisition and associated portfolio of obesity therapeutics including two preclinical oral GLP-1 receptor agonists.
After pulling its own oral GLP-1(AZD0186) in 2023 due to lack of competitive results, AstraZeneca reentered the oral GLP-1 market by striking a deal with Eccogene to license its ECC5004 for the treatment of obesity and type-2 diabetes. ECC5004 (AZD5004) is currently in phase II trials, after achieving positive phase I trials.
Eli Lilly recently announced positive results in its phase III clinical trials of orfoglipron, which is licensed from Chugai Pharmaceutical Co. Ltd. In 2018. Overweight participants without diabetes had an average of 12.4% weight loss, with mild to moderate gastrointestinal side effects such as nausea, vomiting, diarrhea and indigestion. The company is expected to file a NDA by the end of 2025 for the treatment of obesity.
Kailera acquired the rights to four metabolic drugs (outside of China) in May 2024 from Jiangsu Hengrui Pharmaceuticals. The acquisition included Kai7535, a small molecule oral GLP-1 agonist and an oral version of dual agonist KAI-9531. The two oral obesity drugs are in clinical and preclinical phases, respectively.
After safety concerns in phase III of its GLP-1 analog taspoglutide, Roche got back into the obesity market by acquiring Carmot Therapeutics in 2024. The acquisition included the company’s obesity assets CT-338 and CT-996, of which CT-996 was a small molecule oral drug with promising results for activating the GLP-1 receptor. After ramping up the dose to achieve efficacy in phase I, the company reported concerning adverse effects, but allegedly it still plans to enter phase II.
Close Contenders
Though it seems that Novo Nordisk will again be first to the market with an oral solution to weight loss and obesity, there are a number of manufacturers that are not far behind.
Structure Therapeutics is developing a portfolio of oral obesity drugs, with its oral GLP-1 receptor agonist aleniglipron (GSBR-1290) leading the charge. Aleniglipron is in phase 2b trials, with data expected at the end of 2025. The company also has an oral dual amylin and calcitonin receptor agonist (ACCG-2671) that is expected to enter clinicals by the end of 2025.
In early 2025, Viking Therapeutics announced it was entering phase 2 clinical trials for its oral GLP-1 agonist and glucose-dependent insulinotropic polypeptide receptors, Viking VK2735.
Terns has a small molecule GLP-1 receptor agonist (Tern-601) entering phase II trials. Phase I saw moderate weight loss and mild to moderate gastrointestinal side effects common with oral GLP-1 receptor agonists.
Gilead has a small molecule, oral GLP-1 agonist (GS-4571) currently recruiting for phase I clinical trials, with results not expected until mid-2026.
Closing
If all goes well, it looks like Novo Nordisk and Eli Lilly may make it to the market with the first and second oral GLP-1 for obesity and weight loss with other contenders not being far behind. Unfortunately, the gastrointestinal side effects consistent with injectable GLP-1 agonists still remain, but the weight loss in many cases is also comparable to its injectable counterparts. Though long term effects are not known, those suffering from obesity can be hopeful that they will soon have a treatment that is effective, user-friendly, and perhaps more affordable.
Reference