Oral small-molecule GLP-1 receptor agonist safiglipron in early type 2 diabetes: a randomized, double-blind, placebo-controlled trial
Authors' conclusion
These findings support once-daily oral safiglipron as an effective treatment option for type 2 diabetes.
Study context
- Population
- Adults with T2D managed with diet and exercise alone, 46 sites in China (mean baseline HbA1c 7.95%, median diabetes duration 1.6 years, 33.1% women)
- Participants
- 284 adults
- Comparison
- Once-daily oral safiglipron 30, 60 or 90 mg vs placebo
- 30 mgn = 70
- 60 mgn = 70
- 90 mgn = 72
- Placebon = 72reference
- Primary endpoint
- HbA1c change from baseline
- Follow-up
- Week 32
Methodological detailsphase 3, multicenter, double-blind, placebo-controlled, 32 weeks, followed by a 20-week active-treatment extension
- Phase 3
- Multicenter
- Double-blind
- Placebo-controlled
- 32 weeks, followed by a 20-week active-treatment extension
Primary result
As reported in the abstract
Each group vs placeboPlacebo-adjusted treatment difference, % (95% CI)P value
30 mg
−1.22(−1.53 to −0.91)
P < 0.000160 mg
−1.20(−1.52 to −0.89)
P < 0.000190 mg
−1.45(−1.75 to −1.14)
P < 0.0001Secondary outcomes
| Outcome | Placebo | Estimate | P value |
|---|---|---|---|
| HbA1c < 7.0% | 25.0% | ||
| HbA1c ≤ 6.5% | 16.7% | ||
| FPG30 mg vs Placebo | placebo-adjusted difference −1.58 mmol l-1 | P < 0.0001 | |
| FPG60 mg vs Placebo | placebo-adjusted difference −1.68 mmol l-1 | P < 0.0001 | |
| FPG90 mg vs Placebo | placebo-adjusted difference −2.08 mmol l-1 | P < 0.0001 | |
| Body weight30 mg vs Placebo | difference −0.65 % | ||
| Body weight60 mg vs Placebo | difference −2.23 % | ||
| Body weight90 mg vs Placebo | difference −3.56 % |
- HbA1c < 7.0% — HbA1c < 7.0% across safiglipron doses
- 71.4-77.8%
- HbA1c ≤ 6.5% — HbA1c ≤ 6.5% across safiglipron doses
- 58.6-68.1%
- HbA1c < 7.0%: all P < 0.0001
- HbA1c ≤ 6.5%: all P < 0.0001
Other secondary outcomes
- Generally favored safiglipron for HbA1c < 5.7%, postprandial glycemia, HOMA-β, homeostatic model assessment of insulin resistance (HOMA-IR), disposition index and waist circumference, with less rescue therapy use
- Insulin and C-peptide responses varied by dose; changes in treatment satisfaction were limited
Safety
AEs leading to treatment discontinuation
AEs leading to treatment discontinuation
- Gastrointestinal AEs were most common and mostly mild or moderate
Original publication
Oral small-molecule GLP-1 receptor agonist safiglipron in early type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Nat Med. Published 29 September 2026. doi:10.
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