Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes
Authors' conclusion
In adults with early type 2 diabetes, orforglipron significantly reduced the glycated hemoglobin level over a period of 40 weeks.
Study context
- Population
- Adults with T2D treated only with diet and exercise, HbA1c 7.0–9.5%, BMI ≥23.0; mean baseline HbA1c 8.0%randomized 1:1:1:1
- Participants
- 559 adults
- Comparison
- Once-daily oral orforglipron vs placebo
- Primary endpoint
- Change from baseline in HbA1c
- Follow-up
- Week 40
Methodological detailsphase 3, double-blind, placebo-controlled
- Phase 3
- Double-blind
- Placebo-controlled
Primary result
As reported in the abstract
3 mg
−1.24
mean · percentage points
12 mg
−1.47
mean · percentage points
36 mg
−1.48
mean · percentage points
Placebo
−0.41
mean · percentage points
Each group vs placeboEstimated mean difference, percentage points (95% CI)P value
3 mg
−0.83(−1.10 to −0.56)
P < 0.001 for all comparisons12 mg
−1.06(−1.33 to −0.79)
P < 0.001 for all comparisons36 mg
−1.07(−1.33 to −0.81)
P < 0.001 for all comparisonsSecondary outcomes
| Outcome | 3 mg | 12 mg | 36 mg | Placebo |
|---|---|---|---|---|
| Key secondary: percent change in body weight · baseline to week 40 | −4.5% | −5.8% | −7.6% | −1.7% |
HbA1c at week 40 with orforglipron
- Mean HbA1c with orforglipron
- 6.5 to 6.7%
Safety
Adverse events
- Severe hypoglycemia episodes
- 0
- Discontinuation due to AEs, orforglipron
- 4.4 to 7.8%
- Discontinuation due to AEs, placebo
- 1.4%
- Most common AEs: mild-to-moderate gastrointestinal events, mostly during dose escalation
Original publication
Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes. N Engl J Med. Published 21 June 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →