Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study
Errata to this article were published (Lancet, 2 Sep 2023 ↗ · 29 Jun 2024 ↗)
Primary result · Mean change in HbA1cResult — go to the resultEstimated treatment difference −0.8% to −1.7%Authors' conclusion
In this phase 2 trial the novel, oral, non-peptide GLP-1 receptor agonist orforglipron at doses of 12 mg or greater showed significant reductions in HbA1c and bodyweight compared with placebo or dulaglutide. The adverse event profile was similar to other GLP-1 receptor agonists in similar stage of development. Orforglipron might provide an alternative to injectable GLP-1 receptor agonists and oral semaglutide, with the prospect of less burdensome administration to achieve treatment goals in people with type 2 diabetes.
Study context
- Population
- Adults ≥18 years with T2D on diet and exercise ± metformin, HbA1c 7.0–10.5%, stable BMI ≥23 kg/m²; 45 centres in USA, Hungary, Poland, Slovakia303 completed 26 weeks of treatment
- Participants
- 383 adults
- Comparison
- Oral orforglipron vs placebo or dulaglutide 1.5 mg once weekly
- Primary endpoint
- Mean change in HbA1c from baseline with orforglipron vs placebo
- Follow-up
- Week 26
Methodological detailsphase 2, double-blind, multicentre, dose-response
- Phase 2
- Double-blind
- Multicentre
- Dose-response
Primary result
Mean change in HbA1c
Estimated treatment difference
−0.8% to −1.7%
Change by group
Orforglipron
−2.10
mean · %
Placebo
−0.43
mean · %
Dulaglutide
−1.10
mean · %
As reported in the abstract
- Placebo-adjusted HbA1c change with orforglipron (up to)
- −1.67%
Further findings
| Outcome | Orforglipron | Placebo | Dulaglutide |
|---|---|---|---|
| Change in mean bodyweight · week 26kg | −10.1 (95% CI −11.5–-8.7) | −2.2 (CI −3.6–-0.7) | −3.9 (CI −5.3–-2.4) |
| DeathNot related to study treatment | — not stated in the abstract | 1 events | — not stated in the abstract |
— not stated in the abstract
- Change in mean bodyweight — Placebo-adjusted bodyweight change with orforglipron (up to)
- 7.9 kg [−9.9 to −5.9]
- Change in mean bodyweight: orforglipron value is the largest change across doses ("up to")
Safety
| Outcome | Orforglipron | Placebo | Dulaglutide |
|---|---|---|---|
| Treatment-emergent adverse events | 61.8% to 88.9% | 61.8% | 56.0% |
| Gastrointestinal events (mostly mild to moderate) | 44.1% to 70.4% | 18.2% | 34.0% |
| Clinically significant hypoglycaemia (<54 mg/dL [<3 mmol/L]) | 3 events | — not stated in the abstract | 1 events |
— not stated in the abstract
- Clinically significant hypoglycaemia (<54 mg/dL [<3 mmol/L]) — Severe hypoglycaemia
- 0
Original publication
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