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Study decoded · health · Confirmed
Oral GLP-1 Pill Safiglipron Matches Diabetes Pill Dapagliflozin In 810 Adults
810 adults, 32 weeksA1C up to 0.40 pt lowerWeight down 2.4 to 4.2%More GI side effects
An oral small-molecule GLP-1 drug called safiglipron matched or beat the diabetes pill dapagliflozin at lowering blood sugar over 32 weeks, according to a phase 3 trial of 810 adults published in Nature Medicine on October 5, 2026.
Researchers at 98 sites in China randomly assigned 810 adults with type 2 diabetes, average starting A1C 8.60% and average diabetes duration 5 years, to one of three doses of the oral GLP-1 drug safiglipron (30 mg, 60 mg or 90 mg) or to dapagliflozin 10 mg, a standard oral diabetes pill, for 32 weeks, followed by 20 more weeks where everyone stayed on active treatment. Compared with dapagliflozin, safiglipron lowered A1C by an additional 0.30, 0.22 and 0.40 percentage points at the 30 mg, 60 mg and 90 mg doses, meeting the trial's bar for working at least as well as dapagliflozin at all three doses. Under a stricter test for outperforming dapagliflozin, only the 90 mg dose cleared that bar, by 0.25 percentage points. More people hit an A1C under 7.0% on safiglipron (54.9 to 63.5%) than on dapagliflozin (36.5%). Average body weight dropped 2.35% to 4.17% with safiglipron across doses and 3.60% with dapagliflozin. Fewer than 2% of people in any group needed rescue diabetes medication.
GLP-1 receptor agonists work by mimicking a natural gut hormone released after eating that tells the brain you are full, slows how fast food leaves the stomach and helps the pancreas release insulin at the right times. Most versions of this drug class have been injectable; this trial tests the same hormone-mimicking effect delivered as a small-molecule pill, which is why the head-to-head comparison against an established oral diabetes drug like dapagliflozin matters for people who want pill-based options.
A1C Change vs Dapagliflozin by Safiglipron Dose
Data Panel
- Who
- 810 adults with type 2 diabetes, average A1C 8.60%, median diabetes duration 5.0 years, 35.7% women, inadequately controlled on metformin, at 98 sites in China
- Design
- Phase 3, randomized, double-blind, double-dummy, active-comparator-controlled trial (OUTSTAND-2, NCT06589765) comparing three doses of oral safiglipron against dapagliflozin 10 mg
- Dose
- Safiglipron 30 mg, 60 mg or 90 mg daily, or dapagliflozin 10 mg daily, for 32 weeks followed by a 20-week active-treatment extension
- Primary result
- A1C change versus dapagliflozin at week 32: -0.30% (30 mg), -0.22% (60 mg), -0.40% (90 mg); non-inferiority met for all three doses; 90 mg also met the stricter bar for outperforming dapagliflozin
- Secondary
- A1C under 7.0% reached by 54.9-63.5% on safiglipron versus 36.5% on dapagliflozin; body weight dropped 2.35-4.17% with safiglipron versus 3.60% with dapagliflozin; rescue medication used by 0.5-1.5% versus 0%
- Funding / conflicts
- Funding and conflicts not reported in the abstract.
Gastrointestinal side effects, the main safety signal reported, were more frequent with safiglipron and described as mostly mild or moderate. Treatment discontinuation due to side effects occurred in 4.0% on safiglipron 30 mg, 4.0% on 60 mg, 3.9% on 90 mg and 1.5% on dapagliflozin. The trial was conducted only in adults in China inadequately controlled on metformin, and dapagliflozin, not an injectable GLP-1 drug, was the only comparator used.
Dr. Axe's Take
This is a real step for the GLP-1 class: a pill tested head-to-head against a standard diabetes pill rather than a placebo. Safiglipron isn't approved yet, so nothing changes today. For the GLP-1 medicines that are approved, I pair them with a whole-food diet, high protein at every meal, enough fiber to feed gut bacteria, and resistance training to protect muscle while the scale moves. About 4% stopped safiglipron because of side effects, versus 1.5% on dapagliflozin, and stomach complaints were the most common. With approved GLP-1 medicines, many people do well on a much lower dose, often 10 to 20% of the labeled dose, worked out with the prescribing doctor rather than adjusted on their own.
— Dr. Axe