News · Heart & Metabolic
An oral GLP-1 pill cut weight 9% in a phase 2 trial
A trial in Nature Communications tested a once-daily GLP-1 tablet in 235 Chinese adults with obesity. The top dose beat placebo by about 7 percentage points over 26 weeks, with the usual gut side effects.
Based on a randomized, double-blind, placebo-controlled phase 2 trial in 235 adults
- 235 adults with obesity and no diabetes, at 29 centers in China, over 26 weeks.
- Weight fell 9.36% on the top dose against 2.50% on placebo, a gap of 6.87 points.
- The dose ladder was not tidy: 120 mg did slightly worse than 60 mg.
- Gut side effects were the most common, mostly mild, and clustered as doses went up.
- Phase 2 means dose-finding, not proof. No comparison against existing GLP-1 drugs.
Almost every GLP-1 drug in wide use has to be injected, for a dull chemical reason: they are peptides, and the gut digests peptides. A tablet version would change who can realistically take one.
A phase 2 trial in Nature Communications tested a candidate built to survive being swallowed, and it worked well enough to be worth the next stage.
What was tested
Unlike previous GLP-1 drugs, which are injected, this one is a small molecule rather than a peptide, which is the class that tends to survive digestion. The researchers ran a randomized, double-blind, placebo-controlled phase 2 trial conducted at 29 centers in China, and evaluated the efficacy and safety of HRS-7535 in adults with obesity without diabetes.
Excluding people with diabetes matters for reading the result. Blood sugar drugs often produce weight loss as a side effect in people whose blood sugar is high to begin with. Here there was no such confound.
Participants were split across four dose levels and a dummy pill, roughly 46 to 48 people in each. The primary endpoint was percentage change in body weight from baseline to Week 26.
What it found
At the top dose the average loss was 9.36% of body weight, against 2.50% on placebo. Subtracting one from the other leaves 6.87 percentage points that can be attributed to the drug over about six months.
For a phase 2 trial in a class this competitive, that is a result worth continuing with. It is also not a result anyone should compare to an injection without care, and the trial made no such comparison.
The ladder is not tidy
This is the part most coverage will skip. Placebo-adjusted losses ran 0.49% at the lowest dose, then 4.60%, then 3.67%, then 6.87% at the highest.
The third rung sits below the second. With roughly 46 people per arm, a wobble of that size is exactly what chance produces, so the honest reading is that the dose-response relationship is not yet pinned down, rather than that a bigger dose did less.
The trial’s own summary steps around it by grouping doses: once-daily oral HRS-7535 at doses of 60 mg or higher produced clinically meaningful weight loss and was generally well tolerated.
Side effects
Nothing new for the class. Gastrointestinal adverse events were the most common, were predominantly mild to moderate, and occurred more frequently during dose escalation.
That last clause is the practically useful one. The nausea clusters while the dose is being raised, not permanently, which is why these drugs are started low and stepped up slowly.
What this does not settle
Phase 2 is a dose-finding exercise. It exists to decide what to test properly, and it is routinely followed by phase 3 trials that fail to reproduce the early promise.
Twenty-six weeks is also short for a weight drug. The questions that matter to a patient, whether the loss holds, what happens on stopping, and what it does to heart outcomes over years, are all outside this trial.
The population is one country and one body mass range, with no diabetes. And with about 46 people per arm, every individual dose estimate carries a wide margin.
Why it is still worth reporting
The interesting fact is not the 9%. It is that a swallowed small molecule produced a loss in that range at all.
If that holds up in larger trials, the constraint on GLP-1 drugs stops being manufacturing capacity for injectables and starts being something closer to ordinary prescribing. That is a bigger change than a percentage point either way.
People also ask
Why does an oral GLP-1 drug matter when injections already exist?
Because a daily tablet removes the needle, the cold chain and much of the manufacturing constraint that has limited supply of injected GLP-1 drugs. Most existing GLP-1 medicines are peptides, which are destroyed in the gut and so are injected. This one is a small molecule, which is the class of drug that survives being swallowed. That is the point of the whole program.
How does 9% compare with the drugs people already take?
It is lower, and the comparison is not fair. Injected semaglutide and tirzepatide have reported larger losses, but over longer trials and in different populations, and this trial ran 26 weeks in Chinese adults with a body mass index between 28 and 40. Nothing here was tested head to head against another GLP-1 drug, so any ranking is a guess.
Why did the 120 mg dose do worse than 60 mg?
The trial does not resolve it. Placebo-adjusted losses ran -0.49% at 30 mg, -4.60% at 60 mg, -3.67% at 120 mg and -6.87% at 180 mg, so the ladder is not monotonic. With roughly 46 to 48 people per arm, that middle dip is well within what chance can produce. It is a reason to treat the exact dose-response curve as unsettled, not evidence that more drug works less.
What were the side effects?
The pattern familiar from this whole drug class. Gastrointestinal adverse events were the most common, were predominantly mild to moderate, and occurred more frequently during dose escalation, meaning nausea and related complaints clustered while the dose was being raised rather than at steady state. The trial reports it as generally well tolerated at 60 mg and above.
Can I get this?
No. This is a phase 2 trial, which exists to find a dose and check safety signals before larger phase 3 trials decide whether a drug works and is safe enough to license. The compound is not approved anywhere. This is general information about a research result, not medical advice, and decisions about weight-loss medication belong with a doctor.