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Oral small-molecule GLP-1 safiglipron cuts HbA1c in phase 3 diabetes trial

Oral small-molecule GLP-1 safiglipron cuts HbA1c in phase 3 diabetes trial

New Capabilities

Hengrui's once-daily GLP-1 pill posts strong glucose control in two phase 3 trials, with 90 mg beating dapagliflozin on HbA1c

October 2026: OUTSTAND-2 results published in Nature Medicine

Overview

Updated Oct 18

Injectable GLP-1 drugs like Ozempic need needles, and Rybelsus, the first oral version, must be taken on an empty stomach. Lilly's orforglipron, an oral small molecule approved in 2026, avoids that rule. Hengrui's safiglipron is a once-daily pill that also works with food.

Two phase 3 trials published in September and October show safiglipron cuts blood sugar in early diabetes and in patients uncontrolled on metformin. In OUTSTAND-1 (284 patients), placebo-adjusted HbA1c fell 1.20 to 1.45 points, and up to 78% hit the under-7% target; in OUTSTAND-2 (810 patients), all doses matched dapagliflozin, 90 mg beat it, and weight loss reached 4.17%. Gastrointestinal side effects were common, mostly mild to moderate.

Why it matters

Safiglipron could remove the injection and fasting rules from GLP-1 treatment, widening access to a diabetes drug class millions of patients skip today.

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Key Indicators

−4.17%
Body weight change at 90 mg in OUTSTAND-2
Safiglipron 90 mg cut body weight by 4.17% at week 32, versus 3.60% with dapagliflozin.

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Organizations Involved

Jiangsu Hengrui Pharmaceuticals
Jiangsu Hengrui Pharmaceuticals
Pharmaceutical company
Advanced safiglipron through two pivotal phase 3 trials (OUTSTAND-1 and OUTSTAND-2), now awaiting regulatory filing in China

Developer of safiglipron (HRS-7535), a once-daily oral small-molecule GLP-1 receptor agonist.
Eli Lilly and Company
Eli Lilly and Company
Pharmaceutical company
Markets orforglipron, the first approved oral small-molecule GLP-1

Competitor whose oral GLP-1 orforglipron posted phase 3 results in 2025.
Novo Nordisk
Novo Nordisk
Pharmaceutical company
Markets Rybelsus, the peptide oral GLP-1 with fasting requirements

Maker of oral semaglutide (Rybelsus), the first oral GLP-1 approved for type 2 diabetes.

Timeline

September 2019 October 2026

5 events Latest: October 2026
Tap a bar to jump to that date

  1. OUTSTAND-2 results published in Nature Medicine

    Latest Publication

    In 810 patients with type 2 diabetes uncontrolled on metformin, all three safiglipron doses were non-inferior to dapagliflozin on HbA1c; 90 mg met superiority. Weight loss reached 4.17% at 90 mg.

  2. Safiglipron OUTSTAND-1 results published

    Publication

    Placebo-adjusted HbA1c fell 1.20 to 1.45 percentage points; up to 78% of patients hit the under-7% target.

  3. orforglipron posts phase 3 results

    Competition

    Lilly publishes phase 3 data in NEJM, confirming oral small-molecule GLP-1s work (month approximate).

  4. OUTSTAND-1 begins enrolling

    Trial

    284 adults with early type 2 diabetes enter the trial at 46 Chinese sites, randomized to 30, 60, or 90 mg of safiglipron or placebo.

  5. FDA approves Rybelsus, the first oral GLP-1

    Approval

    Oral semaglutide reaches the market but must be taken fasting, with limited water.

Scenarios

1

China's NMPA approves safiglipron for type 2 diabetes

Likely Resolves by End of 2028

Discussed by: Analysts tracking Hengrui's metabolic pipeline

Hengrui built the OUTSTAND program to support registration. With OUTSTAND-1 positive, the company files with China's NMPA, where the drug was studied. Approval would give China a homegrown, injection-free GLP-1 to compete with imported blockbusters. Global licensing deals would likely follow.

2

Safiglipron posts phase 3 weight-loss results

Possible Resolves by End of 2028

Discussed by: Observers citing phase 2 obesity data

Phase 2 showed weight loss in adults with obesity. A phase 3 obesity program would test whether the modest weight effect seen at diabetes doses scales up. Strong results would let Hengrui pitch safiglipron against Lilly's orforglipron in the weight-loss market. Weak results would keep it a diabetes-only drug.

3

Gastrointestinal side effects cap safiglipron's real-world use

Possible Resolves by End of 2029

Discussed by: Concerns raised in the trial's adverse-event profile

GI events hit 73.6% of 90 mg patients, and 6.9% stopped for adverse events at that dose. If real-world persistence mirrors the trial, many patients will tolerate only lower doses, shrinking the efficacy advantage. Payers may steer patients toward alternatives if discontinuation runs high.

Historical Context

2 moments from history that rhyme with this story — and how they unfolded.

September 2019

Oral semaglutide (Rybelsus) approval (2019)

The FDA approved Rybelsus, Novo Nordisk's oral form of semaglutide, as the first oral GLP-1 for type 2 diabetes. It removed the injection barrier but required patients to take it on an empty stomach with limited water each morning.

Then

Opened the oral GLP-1 market and proved patients would accept an oral option.

Now

Left an access gap: the fasting rule and peptide formulation limited convenience, pushing rivals toward small molecules.

Why this matters now

Safiglipron targets exactly the constraint Rybelsus left in place: a pill that works with food, no fasting needed.

June 2025

Orforglipron phase 3 ATTAIN results (2025)

Lilly published phase 3 data in the NEJM showing its oral small-molecule GLP-1, orforglipron, cut HbA1c by 0.83 to 1.07 percentage points versus placebo and produced weight loss of 4.5% to 7.6% at week 40. It became the first approved oral small-molecule GLP-1 receptor agonist.

Then

Validated that non-peptide oral GLP-1s work without injection or fasting constraints.

Now

Set the benchmark safiglipron is now measured against: comparable glucose control, weaker weight effect here.

Why this matters now

Safiglipron is the direct competitor. Its stronger HbA1c numbers and smaller weight effect define the two drugs' competing profiles.

Sources

(7)
+1
Nature Medicine New England Journal of Medicine Journal of Medicinal Chemistry 生物通 (BioTrade) Coios Developments Today Nature Medicine