The pill vs the jab: what we know about oral and injectable semaglutide so far

For most people, the words "weight loss medication" currently conjure an image of a weekly injection. That's understandable, as until recently, the only licensed GLP-1s for weight loss have been injectables. But oral semaglutide is being developed and is currently working its way through regulatory approval.

So what does the clinical evidence actually tell us? And how do the two really compare?

Note: oral semaglutide is not yet approved in the UK.

First, a quick note on comparisons

Before we get into the data, it’s worth noting that the two trials we’re going to reference - OASIS 4 (oral semaglutide) and STEP 1 (injectable semaglutide) - were independent studies run at different times, in different populations, with different sample sizes.^1,2 They weren’t designed to go head-to-head. That means we can look at each set of results on their own terms, but we can’t draw direct conclusions about which formulation is “better” based on the numbers alone.

Same molecule, different challenge

Semaglutide is a GLP-1 receptor agonist, meaning it mimics a hormone your gut naturally produces when you eat, helping to reduce appetite, slow digestion, and support blood sugar regulation.³ In its injectable form, it’s absorbed directly into the bloodstream through the skin. 

The challenge with an oral version is that semaglutide is a peptide, which is the kind of molecule that stomach acid tends to break down before it gets a chance to work.

Oral semaglutide gets around this using something called SNAC (sodium N-[8-(2-hydroxybenzoyl) aminocaprylate]) - a carrier molecule that temporarily modifies the environment around a small area of the stomach lining, allowing semaglutide to pass through and into circulation.⁴

This mechanism comes with specific requirements. The tablet must be taken on an empty stomach, with no more than 120ml of water, followed by a 30-minute wait before eating, drinking, or taking other medications. These are the conditions the formulation is designed to work under.

What the trials found

OASIS 4 - oral semaglutide 25mg

OASIS 4 enrolled 307 adults without diabetes, with a BMI of 30 or above (or 27+ with a weight-related health condition).¹ Participants took oral semaglutide 25mg or a placebo once daily for 64 weeks, alongside lifestyle support. The group was 79% female, with a mean age of 48 and a mean BMI of around 37.

Result: those taking oral semaglutide lost an average of 13.6% of their body weight by week 64, compared with 2.2% in the placebo group.¹

STEP 1 - injectable semaglutide 2.4mg

STEP 1 was a larger trial, enrolling 1,961 adults using the same BMI criteria.² Participants received once-weekly subcutaneous semaglutide 2.4mg or placebo for 68 weeks, with lifestyle support. The group was 73% female, with a mean age of 46 and a mean BMI of 38.

Result: Those taking the injection lost an average of 14.9% of their body weight by week 68, compared with 2.4% in the placebo group.²

Both showed significant results. The numerical gap between them - 13.6% vs 14.9% - is not a basis for concluding one formulation is more effective than the other. Different trials, different people, different conditions.

What about the spread of results?

Both trials also reported what proportion of participants hit specific weight loss thresholds, which gives a more useful picture of the range of responses. These trials are not to be directly compared given they were performed separately under different conditions.

Results varied considerably between individuals in both trials. That’s expected, because how any medication works for you depends on your own biology, lifestyle, and history.

Side effects

Both formulations share the same broad side effects. Gastrointestinal effects (nausea, vomiting, diarrhoea) are the most commonly reported, typically mild to moderate, and most likely during dose escalation.

In OASIS 4, 74% of participants on oral semaglutide reported a GI side effect, compared with 42% on placebo. Nausea was most common (46.6% vs 18.6%), and vomiting occurred in 30.9% vs 5.9%. Around 6.9% stopped treatment due to GI side effects.¹

In STEP 1, nausea was reported in 43.9% on the injection vs 16.1% on placebo. Vomiting occurred in 24.5% vs 6.3%. Around 4.3% discontinued for GI reasons.²

These are trial-setting figures, and real-world tolerability varies. How you get on with either medication is something to work through with your prescriber, who can also help manage side effects if they arise. And remember, just because someone experiences a certain side effect, doesn’t mean you will too.

Beyond the data: practical differences

The oral tablet requires a consistent morning routine: empty stomach, small amount of water, 30-minute wait. That consistency isn’t optional - it directly affects how well the medication works. The injection is once weekly, with no dietary restrictions around the time of administration.

The tablet can be kept at room temperature. The injection needs refrigeration (2–8°C), though it can be unrefrigerated for up to 28 days. For frequent travellers, or anyone without reliable cold storage, this matters.

The oral route  may be preferable for people with needle phobia, or for whom injections simply aren’t suitable.

What does this mean for treatment decisions?

The arrival of oral semaglutide is significant as could expand future treatment options, particularly for those who’ve avoided medication because of injections.

That said, it’s not a straight swap for the injection, and it’s not the right fit for everyone. OASIS 4 and STEP 1 together show that both formulations can deliver meaningful weight loss when combined with lifestyle support. The injectable has a more extensive evidence base, in part because it’s been available for longer. Long-term data for the oral tablet - including cardiovascular outcomes - is still being gathered.

It’s also important to be clear that oral semaglutide isn’t yet licensed in the UK for the management of obesity. Regulatory approval from the MHRA is anticipated, and Numan will only make it available through its services once that approval is in place.

The numan take

Both formulations have solid phase 3 trial evidence behind them. Both produce clinically meaningful weight loss versus placebo, with broadly similar side effects.^1,2 The numbers between the two trials don’t tell us one is better - they tell us both work.

The more useful question isn't which trial showed a bigger number; it's which formulation suits you. If you need help deciding which medication is best for you, our clinicians can support you with this decision.

References

¹ Wharton S, Lingvay I, Bogdanski P, et al. Oral semaglutide at a dose of 25 mg in adults with overweight or obesity. N Engl J Med. 2025;393(11):1077–87.

² Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989–1002.

³ Moore PW, Malone K, VanValkenburg D, et al. GLP-1 agonists for weight loss: pharmacology and clinical implications. Adv Ther. 2023;40(3):723–42.

⁴ Aroda VR, Blonde L, Pratley RE. A new era for oral peptides: SNAC and the development of oral semaglutide for the treatment of type 2 diabetes. Rev Endocr Metab Disord. 2022;23(5):979–94.