The short answer
A daily oral medicine produced weight loss in this early randomized trial, but digestive side effects led some participants to stop treatment.
Who took part?
The phase 2 study enrolled 272 adults with obesity, or overweight plus a weight-related condition, without diabetes. Participants received daily orforglipron at one of four trial doses—12, 24, 36 or 45 mg—or placebo for 36 weeks.
Ranges are across dose groups, not individual responses
Week 26: orforglipron groups
−8.6% to −12.6%
Week 26: placebo
−2.0%
Week 36: orforglipron groups
−9.4% to −14.7%
Week 36: placebo
−2.3%
Original visual based on the study.
| Group or measure | Result |
|---|---|
| Week 26: orforglipron groups | −8.6% to −12.6% |
| Week 26: placebo | −2.0% |
| Week 36: orforglipron groups | −9.4% to −14.7% |
| Week 36: placebo | −2.3% |
What changed?
At the primary 26-week endpoint, average weight change ranged from −8.6% to −12.6% across dose groups, versus −2.0% with placebo.
At week 36, a secondary endpoint, the range was −9.4% to −14.7%, versus −2.3% with placebo. These are ranges across treatment groups, not the range of individual responses.
What were the trade-offs?
Digestive adverse events were most common during dose increases. They led 10–17% of participants in the orforglipron groups to discontinue treatment.
The useful takeaway
This was early evidence, not a comparison with injections or a dosing guide. A small 36-week study cannot answer every long-term safety or maintenance question. Later phase 3 findings from ATTAIN-1 provide additional context.
Sources
Wharton and colleagues, NEJM, 2023. Funded by Eli Lilly.