OASIS 1 shows a daily semaglutide pill can match the injection

A once-daily 50 mg oral semaglutide pill led to an estimated 15.1% average body weight reduction over 68 weeks in adults with overweight or obesity and no type 2 diabetes, compared with 2.4% for placebo, according to results from the phase 3 OASIS 1 trial ^[1].

The trial was a randomized, double-blind, placebo-controlled superiority study run at 50 outpatient clinics in nine countries across Asia, Europe and North America ^[1]. Participants had a body mass index of at least 30, or at least 27 with weight-related complications, and did not have type 2 diabetes ^[1]. From Sept 13 to Nov 22, 2021, 709 people were screened and 667 were randomly assigned 1:1 to oral semaglutide escalated to 50 mg daily (334 people) or matching placebo (333 people), each with a lifestyle intervention, for 68 weeks ^[1].

What the numbers showed

The co-primary endpoints were percentage change in body weight and the share of people reaching at least 5% weight loss at week 68, analyzed regardless of whether participants stopped treatment or used other weight-lowering therapies ^[1].

Estimated mean body weight change was −15.1% (standard error 0.5) with the 50 mg pill versus −2.4% (0.5) with placebo, an estimated treatment difference of −12.7 percentage points (95% CI −14.2 to −11.3; p<0.0001) ^[1].

On the responder endpoints, 269 of 317 participants (85%) on oral semaglutide reached at least 5% weight loss versus 76 of 295 (26%) on placebo (odds ratio 12.6, 95% CI 8.5 to 18.7; p<0.0001) ^[1]. At least 10% loss was reached by 220 (69%) versus 35 (12%); at least 15% by 170 (54%) versus 17 (6%); and at least 20% by 107 (34%) versus 8 (3%) ^[1].

Side effects were more common with the drug. Adverse events of any kind were reported in 307 of 334 participants (92%) taking oral semaglutide and 285 of 333 (86%) taking placebo ^[1]. Gastrointestinal adverse events, described as mostly mild to moderate, occurred in 268 people (80%) on the pill versus 154 (46%) on placebo ^[1].

The trial was funded by Novo Nordisk, and several authors are employees or shareholders of the company; others reported consulting fees or research support from Novo Nordisk and other drugmakers ^[1]. The study is registered as NCT05035095 and is listed as complete ^[1].

An important limit: no head-to-head test

OASIS 1 compared the 50 mg daily pill with placebo, not with injected semaglutide ^[1]. Any comparison to the weekly shot is indirect, based on results from separate trials run in different groups of people. The published report does not include a direct comparison, so how the pill stacks up against the injection in the same patients is not yet known from this source.

Why it matters for patients

Most GLP-1 medicines for weight management in the US are injections. A tablet version that produces double-digit average weight loss could give people who dislike needles, or who have trouble storing and handling injection pens, another option if regulators approve it for weight management ^[1].

The side effect profile looks familiar to anyone who has read about GLP-1 drugs: nausea and other stomach and bowel problems were the dominant complaint, affecting 4 in 5 people on the drug versus fewer than half on placebo, and were mostly mild to moderate ^[1].

It is also worth noting what average results hide. While 85% of people on the pill lost at least 5% of their weight, only about a third reached 20% or more ^[1]. Results varied widely, and about a quarter of placebo participants also hit the 5% mark with lifestyle support alone ^[1].

The trial ran 68 weeks, so it does not answer what happens to weight after stopping the medication, and it enrolled only people without type 2 diabetes ^[1]. Oral semaglutide also has specific dosing instructions in its approved diabetes form; this trial report does not describe real-world adherence outside a study setting.

What happens next

The results were published in The Lancet in 2023, with an accompanying commentary, "Oral semaglutide: an OASIS from injectables," published Aug 26, 2023 ^[1]. The published trial report does not describe regulatory filings, pricing or a US availability date for a 50 mg weight-management pill, so those steps are not yet known from this source.