weight loss
∙5 minute read
Medically reviewed
The arrival of the Wegovy Pill marked the first time a GLP-1 weight loss medication became available in tablet form in the UK. But it won't be the only one for long. Orforglipron, developed by Eli Lilly and approved by the FDA in the US under the brand name Foundayo, is making its way through regulatory review, with UK availability expected later in 2026.
Both are oral GLP-1 medications. Both reduce appetite and produce meaningful weight loss. But they work quite differently at a molecular level, and one of those differences has a practical implication that's worth understanding before either becomes your daily routine.
Orforglipron is a GLP-1 receptor agonist, the same class of medication as semaglutide (Wegovy). It works by mimicking GLP-1, the hormone your gut produces after eating - slowing gastric emptying, reducing appetite signals in the brain, and helping the body manage blood sugar more effectively.¹
Where it differs is in its chemistry. Oral semaglutide is a peptide, meaning it’s the same large, fragile molecule as the injectable version, reformulated for oral delivery using a compound called SNAC to survive the stomach environment.2 Orforglipron, however, is a little different. It’s a small molecule GLP-1 receptor agonist.3 That distinction matters, because small molecules are inherently more stable in the digestive system. They don't need the same chemical engineering to survive being swallowed.
The practical result is the one that will be most obvious to anyone who's been through the oral semaglutide routine, which is that orforglipron doesn’t require a fasted state to be absorbed.²
What does the evidence say about weight loss?
The clinical data for orforglipron comes primarily from the ATTAIN-1 trial, which is a randomised controlled trial in 3,127 adults with obesity, followed for 72 weeks. Participants on the highest dose lost an average of 11.2% of their body weight.3
For comparison, participants on oral semaglutide 25mg in the OASIS 4 trial - 307 adults, 64 weeks - lost an average of 16.6% of their body weight.2
That puts orforglipron slightly behind oral semaglutide on average weight loss at the doses studied so far. It's a meaningful difference, though not a dramatic one, and it's worth noting that trial populations, doses, and durations weren't identical, so direct head-to-head comparisons have limits.
What the data does confirm is that both produce clinically meaningful weight loss, well above what's typically seen with older oral weight loss options.
The side effect profiles of the two medications are broadly similar, because they work through the same GLP-1 receptors. Nausea, diarrhoea, vomiting, and constipation are the most commonly reported effects in trials of both medications, predominantly mild to moderate, most pronounced in the early weeks and at dose increases.2,3
Where they differ slightly is in the oral semaglutide-specific effects caused by SNAC - burping and a metallic aftertaste in the first hour or two after dosing. These don't occur with orforglipron, which doesn't contain SNAC.
Heartburn also tends to be more prominent with oral semaglutide than with injectable GLP-1s, partly due to the SNAC mechanism. Whether orforglipron causes heartburn and related symptoms is still being established from real-world data.
The 30-minute fasting protocol for oral semaglutide is more manageable than it sounds. Once it becomes a habit, many people are stop thinking about it within a few weeks. But it's not entirely straightforward, and for some people it's a genuine obstacle.
If you have an irregular morning schedule, shift work, or a lifestyle that makes a consistent fasting window difficult to sustain, orforglipron's flexibility is a real practical advantage. If your mornings are structured and the routine is working, the difference matters less.
It's also worth noting that the fasting requirement is what makes oral semaglutide work. Miss the protocol and you absorb less of the drug.4 The flexibility of orforglipron removes that variable entirely: what you absorb is much less sensitive to the conditions you take it in.
The Wegovy pill received MHRA approval and is available in the UK from July 2026. Orforglipron is currently pending MHRA review, so UK availability is expected later in 2026, with NICE then determining NHS access.
As with the Wegovy pill, orforglipron is likely to be available through regulated private providers before it reaches NHS prescription. Both are prescription-only medications requiring clinical assessment, and neither is a substitute for the other without a conversation with your clinician.
If you’re wondering which is right for you, the answer is that it honestly depends, and it's a conversation to have together with your clinician.
If you're trying to decide between the two - or between either of them and the injectable options - the relevant factors are your weight loss goals, your lifestyle, your medical history, and how you'd realistically manage each medication day to day. How you tolerate it, how well it works for you, and how it fits into your routine all matter, and the best medication is the one you can actually take consistently.
Müller TD, Finan B, Bloom SR, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019;30:72–130.
Wharton S, Lingvay I, Bogdanski P, et al. Oral semaglutide 25 mg in adults with overweight or obesity (OASIS 4): a randomised, double-blind, placebo-controlled, phase 3a trial. N Engl J Med. 2025;393(11):1077–1087.
Wharton S, Aronne LJ, Stefanski A, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment. N Engl J Med. 2025;393(18):1796–806.
Bækdal TA, Breitschaft A, Donsmark M, Maarbjerg SJ, Søndergaard FL, Anderson TW. Effect of various conditions on the pharmacokinetics of oral semaglutide. J Clin Pharmacol. 2021;61(5):649–659.
Clinical Pharmacist and Copywriter, Master of Pharmacy (MPharm)
