Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity
Authors' conclusion
Daily oral orforglipron, a nonpeptide GLP-1 receptor agonist, was associated with weight reduction. Adverse events reported with orforglipron were similar to those with injectable GLP-1 receptor agonists.
Study context
- Population
- Adults with obesity, or overweight plus ≥1 weight-related coexisting condition, without DM; mean body weight 108.7 kg, mean BMI 37.9randomized
- Participants
- 272 adults
- Comparison
- Once-daily oral orforglipron vs placebo
- Primary endpoint
- Percentage change from baseline in body weight
- Follow-up
- Week 26
Methodological detailsphase 2, double-blind
- Phase 2
- Double-blind
Primary result
As reported in the abstract
Mean % change from baseline in body weight
Orforglipron
−8.6% to −12.6%
mean
Placebo
−2.0%
mean
Secondary outcomes
| Outcome | Orforglipron | Placebo |
|---|---|---|
| Mean % change from baseline in body weight · week 36 | mean −9.4% to −14.7% | mean −2.3% |
| Weight reduction ≥10% · week 36 | 46 to 75% | 9% |
Weight-related and cardiometabolic measures
- Orforglipron improved all prespecified weight-related and cardiometabolic measures
Safety
Gastrointestinal adverse events
- Discontinuation of orforglipron due to GI events across dose cohorts
- 10 to 17%
- Most common AEs with orforglipron were gastrointestinal, mild to moderate, mainly during dose escalation
- Safety profile consistent with the GLP-1 RA class
Original publication
Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. N Engl J Med. Published 23 June 2023. doi:10.
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